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1

Lesion location alters brain activation in chronically impaired stroke survivors  

Microsoft Academic Search

Recovery of motor function after stroke is associated with reorganization in central motor networks. Functional imaging has demonstrated recovery-dependent alterations in brain activation patterns when compared to healthy controls. These alterations are variable across stroke subjects. Factors identified as contributing to this variability are the degree of functional impairment, the time interval since stroke, and rehabilitative therapies. Here, the hypothesis

Andreas R Luft; Sandy Waller; Larry Forrester; Gerald V Smith; Jill Whitall; Richard F Macko; Jörg B Schulz; Daniel F Hanley

2004-01-01

2

Altered Resting-State Brain Activity in Obstructive Sleep Apnea  

PubMed Central

Study Objectives: Structural and functional brain changes may contribute to neural dysfunction in patients with obstructive sleep apnea (OSA). However, the effect of OSA on resting-state brain activity has not been established. The objective of this study was to investigate alterations in resting-state functional connectivity (rsFC) of the common brain networks in patients with OSA and their relationships with changes in gray matter volume (GMV) in the corresponding brain regions. Designs: Resting-state functional and structural MRI data were acquired from patients with OSA and healthy controls. Seven brain networks were identified by independent component analysis. The rsFC in each network was compared between groups and the GMV of brain regions with significant differences in rsFC was also compared. Setting: University hospital. Patients and Participants: Twenty-four male patients with untreated OSA and 21 matched healthy controls. Interventions: N/A. Measurements and Results: OSA specifically affected the cognitive and sensorimotor-related brain networks but not the visual and auditory networks. The medial prefrontal cortex and left dorsolateral prefrontal cortex (DLPFC) showed decreased rsFC and GMV in patients with OSA, suggesting structural and functional deficits. The right DLPFC and left precentral gyrus showed decreased rsFC and unchanged GMV, suggesting a functional deficit. The right posterior cingulate cortex demonstrated increased rsFC and unchanged GMV, suggesting functional compensation. In patients with OSA, the rsFC of the right DLPFC was negatively correlated with the apnea-hypopnea index. Conclusions: OSA specifically affects resting-state functional connectivity in cognitive and sensorimotor-related brain networks, which may be related to the impaired cognitive and motor functions in these patients. Citation: Zhang Q; Wang D; Qin W; Li Q; Chen B; Zhang Y; Yu C. Altered resting-state brain activity in obstructive sleep apnea. SLEEP 2013;36(5):651-659.

Zhang, Quan; Wang, Dawei; Qin, Wen; Li, Qiong; Chen, Baoyuan; Zhang, Yunting; Yu, Chunshui

2013-01-01

3

Maternal immune activation alters fetal brain development through interleukin-6.  

PubMed

Schizophrenia and autism are thought to result from the interaction between a susceptibility genotype and environmental risk factors. The offspring of women who experience infection while pregnant have an increased risk for these disorders. Maternal immune activation (MIA) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism, making MIA a useful model of the disorders. However, the mechanism by which MIA causes long-term behavioral deficits in the offspring is unknown. Here we show that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring. A single maternal injection of IL-6 on day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent inhibition (LI) deficits in the adult offspring. Moreover, coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA prevents the PPI, LI, and exploratory and social deficits caused by poly(I:C) and normalizes the associated changes in gene expression in the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does not result in several of the behavioral changes seen in the offspring of wild-type mice after MIA. The identification of IL-6 as a key intermediary should aid in the molecular dissection of the pathways whereby MIA alters fetal brain development, which can shed new light on the pathophysiological mechanisms that predispose to schizophrenia and autism. PMID:17913903

Smith, Stephen E P; Li, Jennifer; Garbett, Krassimira; Mirnics, Karoly; Patterson, Paul H

2007-10-01

4

Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6  

PubMed Central

Schizophrenia and autism are thought to result from the interaction between a susceptibility genotype and environmental risk factors. The offspring of women who experience infection while pregnant have an increased risk for these disorders. Maternal immune activation (MIA) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism, making MIA a useful model of the disorders. However, the mechanism by which MIA causes long-term behavioral deficits in the offspring is unknown. Here we show that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring. A single maternal injection of IL-6 on day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent inhibition (LI) deficits in the adult offspring. Moreover, coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA prevents the PPI, LI, and exploratory and social deficits caused by poly(I:C) and normalizes the associated changes in gene expression in the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does not result in several of the behavioral changes seen in the offspring of wild-type mice after MIA. The identification of IL-6 as a key intermediary should aid in the molecular dissection of the pathways whereby MIA alters fetal brain development, which can shed new light on the pathophysiological mechanisms that predispose to schizophrenia and autism.

Smith, Stephen E. P.; Li, Jennifer; Garbett, Krassimira; Mirnics, Karoly; Patterson, Paul H.

2008-01-01

5

Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels.  

PubMed

Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. Thirty cannabis users (16 men, 14 women, 18-45 years old) and 30 nondrug user controls (16 men, 14 women, 19-44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and with fMRI using a 3 Tesla scanner during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. The greater but altered brain activities may be mediated by the higher cortisol levels in the cannabis users, which in turn may lead to less efficient visual-motor function. PMID:22159107

King, George R; Ernst, Thomas; Deng, Weiran; Stenger, Andrew; Gonzales, Rachael M K; Nakama, Helenna; Chang, Linda

2011-12-01

6

Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease  

PubMed Central

Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. Objectives: To use fMRI to study brain activation with rivastigmine treatment. Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.

Rombouts, S; Barkhof, F; van Meel, C S; Scheltens, P

2002-01-01

7

Diurnal Alterations of Brain Electrical Activity in Healthy Adults: A LORETA Study  

Microsoft Academic Search

EEG background activity was investigated by low resolution brain electromagnetic tomography (LORETA) to test the diurnal alterations\\u000a of brain electrical activity in healthy adults. Fourteen right-handed healthy male postgraduate medical students were examined\\u000a four times (8 a.m., 2 p.m., 8 p.m. and next day 2 p.m.). LORETA was computed to localize generators of EEG frequency components.\\u000a Comparing the EEG activity between 2 p.m. and 8 a.m.,

Marton Toth; Attila Kiss; Peter Kosztolanyi; Istvan Kondakor

2007-01-01

8

First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo.  

PubMed

The response to centrally acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigated the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 ?g propranolol or 40 ?g propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: (a) lower analgesia in the tail-flick test (p<0.05) and lower areas under the analgesia-time curve (p<0.02) within the first hour after 30 mg/kg subcutaneous codeine, (b) lower morphine concentrations and morphine to codeine ratios in the brain (p<0.02 and p<0.05, respectively), but not in plasma (p>0.6 and p>0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and (c) lower morphine formation from codeine ex vivo by brain membranes (p<0.04), but not by liver microsomes (p>0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p<0.005), but not with plasma morphine concentrations (p>0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally acting drugs. PMID:23623752

Zhou, Kaidi; Khokhar, Jibran Y; Zhao, Bin; Tyndale, Rachel F

2013-04-23

9

Proteolytic activity is altered in brain tissue of rats upon chronic exposure to ozone  

SciTech Connect

Tissue from pons medulla of rats exposed in vivo to various levels of ozone was assayed for calpain and cathepsin D activity. Chronic exposure to ozone increased calpain activity, which was 35% to 46% higher in the homogenates of animals exposed to 1.0 ppm ozone than in those of animals exposed to 0.5 ppm ozone or of controls. An increase in activity of 26% was also observed in the soluble supernatant. The increase in activity did not seem to be caused by ozone effects on calpastatin. Addition of 32 mM carnitine to the incubation mixture increased total activity 3-4 fold, making the differences in activity proportionately smaller. Cathepsin D activity was little altered. Changes in calpain activity and in the generation of free oxygen radicals have been implicated in the aging process, long-term exposure to ozone may magnify changes. Ozone exposure may cause changes in brain protein metabolism. 15 refs., 2 tabs.

Benuck, M.; Banay-Schwartz, M.; Lajtha, A. (N. S. Kline Inst. for Psychiatric Research, Orangeburg, NY (United States))

1993-01-01

10

Altered brain activity in brevetoxin-exposed bluegill, Lepomis macrochirus, visualized using in vivo 14C 2-deoxyglucose labeling  

Microsoft Academic Search

This study investigated the neurological effects of sublethal brevetoxin (PbTx-2) exposure in bluegill (Lepomis macrochirus) by measuring alterations in 2-deoxyglucose (2-DG) uptake in the brains of exposed fish. Changes in regional brain activity were quantified using digitized autoradiographs from exposed and control fish. Brains of brevetoxin-exposed fish had significantly higher labeling of 2-DG than brains of control fish. Regional increases

J. Choich; J. D. Salierno; E. K. Silbergeld; A. S Kane

2004-01-01

11

The concentration of thyroid hormones and activities of iodothyronine deiodinases are altered in human brain gliomas.  

PubMed

We have determined the cellular concentration of thyroxine (T4) and triiodothyronine (T3) and the activities of two brain iodothyronine deiodinases, type II (5'-D2) and type III (5-D3), in two types of tissues --tumour (26) and non-tumour (5), derived either from human gliomas with various histological malignancies or from non-tumoural surrounding brain tissue. As it has been established, all patients before the surgery had the Non-Thyroidal Illness Syndrome (NTIS). The concentration of serum T3 was therefore significantly decreased in all the examined patients. It was over 2.5 times lower than that before surgery and 4.0 times lower at surgery than that seen in healthy controls. The serum concentration of T4 was found to be below normal range in 4/26 cases and in low levels of normal range in 6/26 cases, whereas TSH serum concentration in all patients was within normal range. The concentrations of T3 and T4 (expressed as pg of hormone/mg tissues protein) in 22/26 brain tissue samples were significantly lower in gliomas than in 5 non-tumoural brain tissue samples. As expected, the alternation in brain 5'D II activity in gliomas was seen in most cases with astrocytomas (5/8 cases), gliosarcomas (8/8 cases) and glioblastoma multiforme (10/10 cases). In general, the mean enzyme activity in tumour tissue was significantly higher than that found in non-tumoural tissue of human brain (21.79 fmol of newly generated T3/h/mg of protein vs. 4.88 fmol of T3/h/mg protein, respectively). The highest 5'D2 activity with a range from 10.82 to 45.96 (mean 23.61 fmol T3/h/mg protein) was found in gliosarcomas. The activity of 5-D3 was increased (in 8/8 cases of gliosarcoma and in 9/10 cases of glioblastoma multiforme) or decreased (in 3/3 cases of astrocytoma II, 5/5 cases of astrocytoma III) when compared to mean activity of this enzyme found in non-tumoural brain tissue. In summary, our results suggest that the concentration of brain iodothyronines and metabolism of thyroid hormones in the examined human brain tumours are altered. These changes may be related to malignant progression. PMID:15266780

Nauman, Pawe?; Bonicki, Wies?aw; Michalik, Rados?aw; Warzecha, Adam; Czernicki, Zbigniew

2004-01-01

12

Brain-encysting trematodes and altered monoamine activity in naturally infected killifish Fundulus parvipinnis.  

PubMed

This paper presents novel evidence to address mechanisms by which trematode parasites effect behavioural changes in naturally infected fish hosts. California killifish Fundulus parvipinnis infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours that render them 30 times more likely to be eaten by birds, the parasite's final host. Prevalence of E. californiensis reaches nearly 100% in most F. parvipinnis populations, with parasite biomass constituting almost 2% of F. parvipinnis biomass in some locations. Despite having thousands of cysts on their brains, infected fish grow and mature at rates comparable to those of uninfected populations. The lack of general pathology combined with the specificity of the altered behaviours suggests that the behavioural changes are due to parasite manipulation. The monoamine neurotransmitters serotonin and dopamine, which control locomotion and social behaviour in fishes and other vertebrates, were examined to explore the underlying mechanisms of this behaviour modification. Whereas previous studies were similarly conducted with experimentally infected fish, in this study, brain dopaminergic and serotonergic activity were analysed in naturally infected fish to assess how E. californiensis may alter F. parvipinnis monoamines in a naturally occurring system. A parasite density-associated decrease in serotonergic activity occurred in the hippocampus of naturally infected fish, as well as a decrease in dopaminergic activity in the raphe nuclei, suggesting that E. californiensis inhibits serotonin and dopamine signaling in naturally infected F. parvipinnis. The neurochemical profile of infected fish is consistent with the hypothesis that E. californiensis affects brain monoaminergic systems in order to induce impulse-driven, active, and aggressive behaviour in its hosts. PMID:23252735

Shaw, J C; Øverli, Ø

2012-09-05

13

Altered Error-Related Brain Activity in Youth with Major Depression  

PubMed Central

Depression is associated with impairments in cognitive control including action monitoring processes, which involve the detection and processing of erroneous responses in order to adjust behavior. Although numerous studies have reported altered error-related brain activity in depressed adults, relatively little is known about age-related changes in error-related brain activity in depressed youth. This study focuses on the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) that is maximal approximately 50 ms following errors. High-density ERPs were examined following responses on a flanker task in 24 youth diagnosed with MDD and 14 low-risk healthy controls (HC). Results indicate that compared to HC, MDD youth had significantly smaller ERN amplitudes and did not exhibit the normative increases in ERN amplitudes as a function of age. Also, ERN amplitudes were similar in depressed youth with and without comorbid anxiety. These results suggest that depressed youth exhibit different age-related changes in brain activity associated with action monitoring processes. Findings are discussed in terms of existing work on the neural correlates of action monitoring and depression and the need for longitudinal research studies investigating the development of neural systems underlying action monitoring in youth diagnosed with and at risk for depression.

Ladouceur, Cecile D.; Slifka, John S.; Dahl, Ronald E.; Birmaher, Boris; Axelson, David A.; Ryan, Neal D.

2012-01-01

14

Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer’s disease  

Microsoft Academic Search

Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer’s disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition.Objectives: To use fMRI to study brain activation with rivastigmine

S A R B Rombouts; F Barkhof; C S van Meel; P Scheltens

2002-01-01

15

Alterations in Regional Homogeneity of Spontaneous Brain Activity in Late-Life Subthreshold Depression  

PubMed Central

The early detection of major depression in elderly individuals who are at risk of developing the disease is of prime importance when it comes to the prevention of geriatric depression. We used resting-state functional magnetic resonance imaging (fMRI) to examine changes in regional homogeneity (ReHo) of spontaneous activity in late-life subthreshold depression (StD), and we evaluated the sensitivity/specificity performance of these changes. Nineteen elderly individuals with StD and 18 elderly controls underwent a resting-state fMRI scan. The ReHo approach was employed to examine whether StD was related to alterations in resting-state neural activity, in the form of abnormal regional synchronization. Receiver operating characteristic curve analysis and the Fisher stepwise discriminant analysis were used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the StD subjects and normal controls. The results demonstrated that, compared to controls, StD subjects display lower ReHo in the right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left postcentral gyrus (PCG), and left middle frontal and inferior temporal gyri, as well as higher ReHo in the bilateral insula and right DLPFC. The left PCG and the right DLPFC, OFC, and posterior insula, together reported a predictive accuracy of 91.9%. These results suggest that the regional activity coherence was changed in the resting brain of StD subjects, and that these alterations may serve as potential markers for the early detection of StD in late-life depression.

Yu, Jing; He, Yong; Li, Juan

2013-01-01

16

Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery.  

PubMed

Objective:Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment.Design:Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment.Results:As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women.Conclusion:Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.International Journal of Obesity advance online publication, 28 May 2013; doi:10.1038/ijo.2013.60. PMID:23711773

Frank, S; Wilms, B; Veit, R; Ernst, B; Thurnheer, M; Kullmann, S; Fritsche, A; Birbaumer, N; Preissl, H; Schultes, B

2013-04-29

17

Activity Wheel Running Reduces Escape Latency and Alters Brain Monoamine Levels After Footshock  

Microsoft Academic Search

We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (?50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9–12 weeks, animals were matched in pairs on body mass. Activity wheel animals

R. K Dishman; K. J Renner; T. G Reigle; B. N Bunnell; K. A Burke; H. S Yoo; E. H Mougey; J. L Meyerhoff

1997-01-01

18

The Unrested Resting Brain: Sleep Deprivation Alters Activity within the Default-mode Network  

Microsoft Academic Search

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting

Ninad Gujar; Seung-Schik Yoo; Peter Hu; Matthew P. Walker

2009-01-01

19

The Unrested Resting Brain: Sleep Deprivation Alters Activity within the Default-mode Network  

Microsoft Academic Search

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we re- port that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation,

Ninad Gujar; Seung-Schik Yoo; Peter Hu; Matthew P. Walker

2010-01-01

20

Brain transections selectively alter ingestion and behavioral activation in neonatal rats  

Microsoft Academic Search

Food-deprived neonatal rats actively ingest milk that is infused into their mouths through intraoral cannulas. This ingestion is accompanied by behavioral activation. The involvement of various brain regions in ingestion and activation was examined in 2-day-old Charles River pups by making transections along the neuraxis from the olfactory bulbs to the anterior pons. Following a 24-hr deprivation period, a series

Carol L. Kornblith; Warren G. Hall

1979-01-01

21

The hyperactive syndrome: Metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity  

Microsoft Academic Search

The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal

Davide Viggiano

2008-01-01

22

Estradiol treatment altered anticholinergic-related brain activation during working memory in postmenopausal women  

PubMed Central

Estradiol has been shown to affect cholinergic modulation of cognition in human and nonhuman animal models. This study examined the brain-based interaction of estradiol treatment and anticholinergic challenge in postmenopausal women during the performance of a working memory task and functional MRI. Twenty-four postmenopausal women were randomly and blindly placed on 1 mg oral 17-? estradiol or matching placebo pills for three months after which they participated in three anticholinergic challenge sessions. During the challenge sessions, subjects were administered the antimuscarinic drug scopolamine, the antinicotinic drug mecamylamine, or placebo. After drug administration, subjects completed a fMRI session during which time they performed a visual verbal N-back test of working memory. Results showed that scopolamine increased activation in the left medial frontal gyrus (BA 10) and mecamylamine increased activation in the left inferior frontal gyrus (BA 46). Estradiol treatment compared to placebo treatment significantly reduced the activation in this left medial frontal region during scopolamine challenge. Estradiol treatment also increased activation in the precuneus (BA 31) during mecamylamine challenge. These data are the first to show that estradiol modulated antimuscarinic- and anitnicotinic-induced brain activity and suggest that estradiol affected cholinergic system regulation of cognition-related brain activation in humans.

Dumas, Julie A.; Kutz, Amanda M.; Naylor, Magdalena R.; Johnson, Julia V.; Newhouse, Paul A.

2012-01-01

23

Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura.  

PubMed

Although previous resting-state studies have reported abnormal functional cerebral changes in patients with migraine without aura (MwoA), few have focused on alterations in both regional spontaneous neuronal activity and corresponding brain circuits in MwoA patients during rest. Eighteen MwoA patients and 18 age- and gender-matched healthy controls (HC) were recruited in the current study. Baseline cerebral alterations were investigated using amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) analyses. Compared with HC, MwoA patients showed decreased ALFF values in the left rostral anterior cingulate cortex (rACC) and bilateral prefrontal cortex (PFC) as well as increased ALFF values in the right thalamus. FC analysis also revealed abnormal FCs associated with these ROIs. In addition, ALFF values of the left rACC correlated with duration of disease in MwoA. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in MwoA, providing both regional and brain circuit spontaneous neuronal activity properties. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23348909

Xue, Ting; Yuan, Kai; Cheng, Ping; Zhao, Ling; Zhao, Limei; Yu, Dahua; Dong, Tao; von Deneen, Karen M; Gong, Qiyong; Qin, Wei; Tian, Jie

2013-01-24

24

Neuronal overexpression of cyclooxygenase-2 does not alter the neuroinflammatory response during brain innate immune activation  

PubMed Central

Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases and cyclooxygenases (COX) -1 and -2 are key regulators of innate immune responses. We recently demonstrated that COX-1 deletion attenuates, whereas COX-2 deletion enhances, the neuroinflammatory response, blood-brain barrier permeability and leukocyte recruitment during lipopolysaccharide (LPS)-induced innate immune activation. Here, we used transgenic mice, which overexpressed human COX-2 via neuron-specific Thy-1 promoter (TgCOX-2), causing elevated prostaglandins (PGs) levels. We tested whether neuronal COX-2 overexpression affects the glial response to a single intracerebroventricular injection of LPS, which produces a robust neuroinflammatory reaction. Relative to non transgenic controls (NTg), 7 month-old TgCOX2 did not show any basal neuroinflammation, as assessed by gene expression of markers of inflammation and oxidative stress, neuronal damage, as assessed by Fluoro-JadeB staining, or systemic inflammation, as assessed by plasma levels of IL-1? and corticosterone. Twenty-four hours after LPS injection, all mice showed increased 1) microglial activation, as indicated by Iba1 immunostaining, 2) neuronal damage, 3) mRNA expression of cytokines (TNF-?, IL-6), reactive oxygen expressing enzymes (iNOS and NADPH oxidase subunits), endogenous COX-2, cPLA2 and mPGES-1, 4) hippocampal and cortical IL-1? levels. However, the increases were similar in TgCOX-2 and NTg. In NTg, LPS increased brain PGE2 to the levels observed in TgCOX2. These results suggest that PGs derived from neuronal COX-2 do not play a role in the neuroinflammatory response to acute activation of brain innate immunity. This is likely due to the direct effect of LPS on glial rather than neuronal cells.

Aid, Saba; Parikh, Nishant; Palumbo, Sara; Bosetti, Francesca

2010-01-01

25

Neuronal overexpression of cyclooxygenase-2 does not alter the neuroinflammatory response during brain innate immune activation.  

PubMed

Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases and cyclooxygenases (COX)-1 and -2 are key regulators of innate immune responses. We recently demonstrated that COX-1 deletion attenuates, whereas COX-2 deletion enhances, the neuroinflammatory response, blood-brain barrier permeability and leukocyte recruitment during lipopolysaccharide (LPS)-induced innate immune activation. Here, we used transgenic mice, which overexpressed human COX-2 via neuron-specific Thy-1 promoter (TgCOX-2), causing elevated prostaglandins (PGs) levels. We tested whether neuronal COX-2 overexpression affects the glial response to a single intracerebroventricular injection of LPS, which produces a robust neuroinflammatory reaction. Relative to non-transgenic controls (NTg), 7 month-old TgCOX-2 did not show any basal neuroinflammation, as assessed by gene expression of markers of inflammation and oxidative stress, neuronal damage, as assessed by Fluoro-JadeB staining, or systemic inflammation, as assessed by plasma levels of IL-1beta and corticosterone. Twenty-four hours after LPS injection, all mice showed increased microglial activation, as indicated by Iba1 immunostaining, neuronal damage, mRNA expression of cytokines (TNF-alpha, IL-6), reactive oxygen expressing enzymes (iNOS and NADPH oxidase subunits), endogenous COX-2, cPLA(2) and mPGES-1, and hippocampal and cortical IL-1beta levels. However, the increases were similar in TgCOX-2 and NTg. In NTg, LPS increased brain PGE(2) to the levels observed in TgCOX-2. These results suggest that PGs derived from neuronal COX-2 do not play a role in the neuroinflammatory response to acute activation of brain innate immunity. This is likely due to the direct effect of LPS on glial rather than neuronal cells. PMID:20451580

Aid, Saba; Parikh, Nishant; Palumbo, Sara; Bosetti, Francesca

2010-05-06

26

Frequency Dependent Alterations in Regional Homogeneity of Baseline Brain Activity in Schizophrenia  

PubMed Central

Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5?0.01–0.027 Hz; slow-4?0.027–0.08 Hz; and typical band: 0.01–0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent.

Wang, Hsiao-Lan Sharon; Liu, Chih-Min; Liu, Chen-Chung; Hwang, Tzung-Jeng; Chien, Yi-Ling; Hwu, Hai-Gwo; Tseng, Wen-Yih Isaac

2013-01-01

27

Frequency dependent alterations in regional homogeneity of baseline brain activity in schizophrenia.  

PubMed

Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5:0.01-0.027 Hz; slow-4:0.027-0.08 Hz; and typical band: 0.01-0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent. PMID:23483911

Yu, Rongjun; Hsieh, Ming H; Wang, Hsiao-Lan Sharon; Liu, Chih-Min; Liu, Chen-Chung; Hwang, Tzung-Jeng; Chien, Yi-Ling; Hwu, Hai-Gwo; Tseng, Wen-Yih Isaac

2013-03-06

28

Early and Later Life Stress Alter Brain Activity and Sleep in Rats  

PubMed Central

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

Mrdalj, Jelena; Pallesen, Stale; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bj?rn; Gr?nli, Janne

2013-01-01

29

A History Of Iron Deficiency Anemia During Infancy Alters Brain Monoamine Activity Later In Juvenile Monkeys  

PubMed Central

Both during and after a period of iron deficiency (ID), iron-dependent neural processes are affected, which raises the potential concern that the anemia commonly experienced by many growing infants could have a protracted effect on the developing brain. To further investigate the effects of ID on the immature brain, 49 infant rhesus monkeys were evaluated across the first year of life. The mothers, and subsequently the infants after weaning, were maintained on a standardized diet containing 180 mg/kg of iron and were not provided other iron-rich foods as treats or supplements. As the infants grew, they were all screened with hematological tests, which documented that 16 (33.3%) became markedly ID between 4-to-8 months of age. During this anemic period and subsequently at one year of age, cerebrospinal fluid (CSF) specimens were collected to compare monoamine activity in the ID and iron-sufficient infants. Monoamine neurotransmitters and metabolite levels were normal at 4 and 8 months of age, but by one year the formerly anemic monkeys had significantly lower dopamine and significantly higher norepinephrine levels. These findings indicate that ID can affect the developmental trajectory of these two important neurotransmitter systems, which are associated with emotionality and behavioral performance, and further that the impact in the young monkey was most evident during the period of recovery.

Coe, Christopher L.; Lubach, Gabriele R.; Bianco, Laura; Beard, John L.

2009-01-01

30

Diet fat alters synaptosomal phosphatidylethanolaminemethyl-transferase activity and phosphatidylcholine synthesis in brain  

SciTech Connect

Phosphatidylcholine (PC) can be synthesized via three routes, each having potentially different metabolic fates. One route for PC synthesis is methylation of phosphatidylethanolamine (PE). To examine if dietary fat affects membrane PE composition and phosphatidylethanolaminemethyltransferase (PEMT) activity, male weanling rats were fed semi-purified diets containing 20% (w/w) fat of differing fatty acid composition for 24 days. Microsomal and synaptic plasma membranes were isolated and phospholipid composition analyzed. PEMT activity was measured by incorporation of the methyl group from /sup 3/H-S-adenosylmethionine into PE. Polyunsaturated diets high in omega 6 fatty acids produce a high ratio of omega 6/omega 3 fatty acids in synaptic plasma membranes. Dietary omega 3 and omega 6 fatty acid levels are reflected in membrane phospholipid content of 22:6(3), 20:4(6), 22:4(6) and 22:5(6). Diet-induced increase in these longer chain homologues of omega 6 and omega 3 fatty acids and a high ratio of omega 6/omega 3 fatty acids in PE are both associated with increased PEMT activity. These results suggest that diet-fat induced change in fatty acid composition of membrane PE results in transition in PEMT activity and synthesis of PC in brain, by providing preferred species of PE for methylation.

Hargreaves, K.M.; Clandinin, M.T.

1986-03-05

31

Altered Brain Activation in Ventral Frontal-Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive-Compulsive Disorder  

PubMed Central

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.

Han, Ji Yeon; Kang, Do-Hyung; Gu, Bon-Mi; Jung, Wi Hoon; Choi, Jung-Seok; Choi, Chi-Hoon; Jang, Joon Hwan

2011-01-01

32

Changes in brain calpain activity as a result of in vitro ischemia and pH alterations  

Microsoft Academic Search

Calpains and calpastatin in the brain of the rabbit were examined in experimental situations that could mimic some features\\u000a of brain ischemia. Incubations of bisected brains in saline at 39°C for 0.5, 1, or 1.5 h resulted in a decreased calpain I\\u000a activity in the cytosol and in an increased hydrophobicity of cytosolic calpain II activity. Incubation of brain homogenates

Elisabeth Nilsson; Klas Ostwald; Jan-Olof Karlsson

1991-01-01

33

Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI  

Microsoft Academic Search

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01–0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0±1.4 years)

Zang Yu-Feng; He Yong; Zhu Chao-Zhe; Cao Qing-Jiu; Sui Man-Qiu; Liang Meng; Tian Li-Xia; Jiang Tian-Zi; Wang Yu-Feng

2007-01-01

34

Alterations in regional homogeneity of resting-state brain activity in internet gaming addicts  

PubMed Central

Backgrounds Internet gaming addiction (IGA), as a subtype of internet addiction disorder, is rapidly becoming a prevalent mental health concern around the world. The neurobiological underpinnings of IGA should be studied to unravel the potential heterogeneity of IGA. This study investigated the brain functions in IGA patients with resting-state fMRI. Methods Fifteen IGA subjects and fourteen healthy controls participated in this study. Regional homogeneity (ReHo) measures were used to detect the abnormal functional integrations. Results Comparing to the healthy controls, IGA subjects show enhanced ReHo in brainstem, inferior parietal lobule, left posterior cerebellum, and left middle frontal gyrus. All of these regions are thought related with sensory-motor coordination. In addition, IGA subjects show decreased ReHo in temporal, occipital and parietal brain regions. These regions are thought responsible for visual and auditory functions. Conclusions Our results suggest that long-time online game playing enhanced the brain synchronization in sensory-motor coordination related brain regions and decreased the excitability in visual and auditory related brain regions.

2012-01-01

35

Altered brain activity processing in high-anxiety rodents revealed by challenge paradigms and functional mapping  

Microsoft Academic Search

Pathological anxiety involves aberrant processing of emotional information that is hypothesized to reflect perturbations in fear\\/anxiety pathways. The affected neurobiological substrates in patients with different anxiety disorders are just beginning to be revealed. Important leads for this research can be derived from findings obtained in psychopathologically relevant rodent models of enhanced anxiety, by revealing where in the brain neuronal processing

Nicolas Singewald

2007-01-01

36

Relationships between locomotor activation and alterations in brain temperature during selective blockade and stimulation of dopamine transmission  

Microsoft Academic Search

It is well known that the dopamine (DA) system plays an essential role in the organization and regulation of brain activational processes. Various environmental stimuli that induce locomotor activation also increase DA transmission, while DA antagonists decrease spontaneous locomotion. Our previous work supports close relationships between locomotor activation and brain and body temperature increases induced by salient environmental challenges or

P. L. Brown; D. Bae; E. A. Kiyatkin

2007-01-01

37

Growth, Adipose, Brain, and Skin Alterations Resulting from Targeted Disruption of the Mouse Peroxisome Proliferator-Activated Receptor ?(?)  

PubMed Central

To determine the physiological roles of peroxisome proliferator-activated receptor ? (PPAR?), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPAR? gene. Homozygous PPAR?-null term fetuses were smaller than controls, and this phenotype persisted postnatally. Gonadal adipose stores were smaller, and constitutive mRNA levels of CD36 were higher, in PPAR?-null mice than in controls. In the brain, myelination of the corpus callosum was altered in PPAR?-null mice. PPAR? was not required for induction of mRNAs involved in epidermal differentiation induced by O-tetradecanoylphorbol-13-acetate (TPA). The hyperplastic response observed in the epidermis after TPA application was significantly greater in the PPAR?-null mice than in controls. Inflammation induced by TPA in the skin was lower in wild-type mice fed sulindac than in similarly treated PPAR?-null mice. These results are the first to provide in vivo evidence of significant roles for PPAR? in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation.

Peters, Jeffrey M.; Lee, Susanna S. T.; Li, Wen; Ward, Jerrold M.; Gavrilova, Oksana; Everett, Carrie; Reitman, Marc L.; Hudson, Lynn D.; Gonzalez, Frank J.

2000-01-01

38

Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia.  

PubMed

Tardive dyskinesia (TD) is an iatrogenic syndrome being a significant adverse outcome of typical and atypical antipsychotic therapy. Recently we demonstrated that vitamins B (B1, B6, B12 alone or in combination) were able to prevent haloperidol-induced orofacial dyskinesia (OD) possibly by their antioxidant activity in the striatum, using a well-established model of TD. Here, based on the fact that alterations in cholinergic neurotransmission are related to TD pathophysiology and that vitamins B seems to influence brain cholinergic neurotransmission, we decided to investigate the effects of vitamins B1, B6, B12 and their association, vitamin B cocktail in haloperidol-induced cholinergic alterations, evaluated by alterations in acetylcholinesterase (AChE) activity, in striatum, prefrontal cortex and hippocampus, as a way to determine the participation of cholinergic neurotransmission, in these vitamins antidyskinetic mechanism. Haloperidol 1 mg/kg?i.p. daily administration during 21 days to Wistar rats caused OD while decreased AChE activity in all brain areas studied. Vitamins B administration (B1:B6:B12 at 60:60:0.6 mg/kg, s.c) alone and vitamin B cocktail co-administered with haloperidol prevented OD development and increased AChE activity in all brain areas studied, with the maximum activity increment observed in the hippocampus of the animals co-treated with vitamin B12 and vitamin B cocktail. The antidyskinetic drug, clozapine did not induce OD and increased AChE activity similarly to the groups coadministered with vitamin B and HAL. The present data suggest that vitamins B can prevent haloperidol-induced alterations in AChE activity what can be related to the mechanism underlying their antidyskinetic effect. PMID:23095989

de Oliveira, Gersilene Valente; Gomes, Patrícia Xavier Lima; de Araújo, Fernanda Yvelize Ramos; Vasconcelos, Silvânia Maria Mendes; Júnior, Hélio Vitoriano Nobre; de Sousa, Francisca Cléa Florenço; de Lucena, David F; Hyphantis, Thomas N; Carvalho, André Férrer; Macêdo, Danielle Silveira

2012-10-25

39

Prenatal cocaine and morphine alter brain cyclin-dependent kinase 5 (Cdk5) activity in rat pups  

Microsoft Academic Search

Pregnant rats received daily injections of saline, cocaine (20 mg\\/kg), morphine (2 mg\\/kg), or the combination of both drugs, on days 13–20 of gestation. Cyclin-dependent kinase 5 (Cdk5) activity was then measured in the resulting pups on postnatal days 1, 7, 14 and 28. Cocaine resulted in a time dependent increase in brain Cdk5 activity which peaked on day 14. Morphine, in

Rama Bhat; Gopal Chari; Ravi Rao; David Wirtshafter

2006-01-01

40

Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability  

PubMed Central

Reading disability (RD) is a complex genetic disorder with unknown etiology. Genes on chromosome 6p22, including DCDC2, KIAA0319, and TTRAP, have been identified as RD associated genes. Imaging studies have shown both functional and structural differences between brains of individuals with and without RD. There are limited association studies performed between RD genes, specifically genes on 6p22, and regional brain activation during reading tasks. Using fourteen variants in DCDC2, KIAA0319, and TTRAP and exhaustive reading measures, we first tested for association with reading performance in 82 parent-offspring families (326 individuals). Next, we determined the association of these variants with activation of sixteen brain regions of interest during four functional magnetic resonance imaging-reading tasks. We nominally replicated associations between reading performance and variants of DCDC2 and KIAA0319. Furthermore, we observed a number of associations with brain activation patterns during imaging-reading tasks with all three genes. The strongest association occurred between activation of the left anterior inferior parietal lobe and complex tandem repeat BV677278 in DCDC2 (uncorrected p=0.00003, q=0.0442). Our results show that activation patterns across regions of interest in the brain are influenced by variants in the DYX2 locus. The combination of genetic and functional imaging data show a link between genes and brain functioning during reading tasks in subjects with RD. This study highlights the many advantages of imaging data as an endophenotype for discerning genetic risk factors for RD and other communication disorders and underscores the importance of integrating neurocognitive, imaging, and genetic data in future investigations.

Cope, Natalie; Eicher, John D.; Meng, Haiying; Gibson, Christopher J.; Hager, Karl; Lacadie, Cheryl; Fulbright, Robert K.; Constable, R. Todd; Page, Grier P.; Gruen, Jeffrey R.

2012-01-01

41

Hind Limb Unloading Model Alters Nuclear Factor kappa B and Activator Protein-1 Signaling in Mouse Brain  

NASA Astrophysics Data System (ADS)

Microgravity induces inflammatory response and also modulates immune functions, which may increase oxidative stress. Exposure to the microgravity environment induces adverse neurological effects. However, there is little research exploring the etiology of neurological effects of exposure to this environment. To explore this area we evaluated changes in Nuclear Factor kappa B, Activator Protein 1, MAPP kinase and N terminal c-Jun kinase in mouse brain exposed to a simulated microgravity environment using the hindlimb unloading model. BALB/c male mice were randomly assigned to hindlimb unloading group (n=12) and control group (n=12) to simulate a microgravity environment, for 7 days. Changes observed in NF-?B, AP- 1 DNA binding, MAPKK and N terminal c-Jun kinase were measured using electrophoretic mobility shift assay (EMSA) and western blot analysis and compared to unexposed brain regions. Hindlimb unloading exposed mice showed significant increases in generated NF-?B, AP-1, MAPKK and Kinase in all regions of the brain exposed to hindlimb unloading as compared to the control brain regions. Results suggest that exposure to simulated microgravity can induce expression of certain transcription factors and protein kinases. This work was supported by funding from NASA NCC 9-165. 504b030414000600080000002100828abc13fa0000001c020000130000005b436f6e74656e745f54797065735d2e78

Ramesh, Govindarajan; Vani, Vani; Renard, Renard; Vera, Vera; Wilosn, Wilosn; Ramesh, Govindarajan

42

Exercise Improves Executive Function and Achievement and Alters Brain Activation in Overweight Children: A Randomized Controlled Trial  

PubMed Central

Objective This experiment tested the hypothesis that exercise would improve executive function. Design Sedentary, overweight 7- to 11-year-old children (N = 171, 56% female, 61% Black, M ± SD age 9.3 ± 1.0 yrs, body mass index (BMI) 26 ± 4.6 kg/m2, BMI z-score 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 minutes/day), or a control condition. Main outcome measures Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional magnetic resonance imaging measured brain activity during executive function tasks. Results Intent to treat analysis revealed dose response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity due to exercise was also observed. Conclusion Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes due to exercise were observed. The cognitive and achievement results add evidence of dose response, and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children’s mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity.

Davis, Catherine L.; Tomporowski, Phillip D.; McDowell, Jennifer E.; Austin, Benjamin P.; Miller, Patricia H.; Yanasak, Nathan E.; Allison, Jerry D.; Naglieri, Jack A.

2010-01-01

43

Altered Calcium Signaling Following Traumatic Brain Injury  

PubMed Central

Cell death and dysfunction after traumatic brain injury (TBI) is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI.

Weber, John T.

2012-01-01

44

Brain mitochondrial alterations after chronic alcohol consumption.  

PubMed

The aim of this study was to demonstrate the existence of alterations in glutathione and cholesterol homeostasis in brain mitochondria from alcoholic rats. Glutathione concentration decreased, whereas oxidized glutathione and cholesterol contents increased in these organelles, suggesting the ethanol-induced generation of reactive oxygen species, and the impairment of mitochondrial uptake of glutathione, possibly due to the increase in cholesterol deposition. The release of apoptogenic proteins was increased after stimulating mitochondria from the brain of alcoholic rats with atractyloside. As a conclusion, chronic alcohol consumption might sensitize brain mitochondria to apoptotic stimuli, and promote the subsequent release of apoptotic proteins. PMID:20119825

Almansa, I; Fernández, A; García-Ruiz, C; Muriach, M; Barcia, J M; Miranda, M; Fernández-Checa, J C; Romero, F J

2009-09-01

45

Activation changes in zebra finch (Taeniopygia guttata) brain areas evoked by alterations of the earth magnetic field.  

PubMed

Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds. PMID:22679515

Keary, Nina; Bischof, Hans-Joachim

2012-06-05

46

Reduced anesthetic requirements in aged rats: association with altered brain synaptic plasma membrane Ca(2+)-ATPase pump and phospholipid methyltransferase I activities.  

PubMed

Aging is associated with a decrease in anesthetic requirements. Animal models of aging manifest alteration of brain Ca2+ homeostasis and increased methyltransferase I (PLMTI) activity. In this study we evaluated concurrently anesthetic requirements and brain plasma membrane Ca(2+)-ATPase (PMCA) and PLMTI activities in young and aged rats. Halothane, desflurane, isoflurane and xenon MEDs (lowest partial pressures that suppress a pain response) were measured in 2 and 25 month old, male Fisher-344 rats. Halothane MED was also measured in 2 and 30 month old F344/BNF1 rats, a strain that undergoes aging with less debilitation. PMCA pumping and PLMTI activities were measured in synaptic plasma membranes (SPM) prepared from the cortex and diencephalon-mesencephalon (DM). For aged Fisher-344 rats, MEDs for halothane, desflurane, isoflurane and xenon were reduced to 81%, 82%, 67% and 86%, respectively, of young controls; PMCA activity was diminished to 91% in cortical SPM and 82% in DM SPM; and cortical and DM PLMTI activities were increased to 131% and 114% of young control. For F344/BNF1 rats, MED for halothane was reduced to 87%, PMCA activity was diminished to 90% in cortical SPM and 72% DM SPM, and PLMTI activity was increased to 133% in cortical SPM and 112% in DM SPM. The strong association between age and reduced anesthetic requirements for inhalational agents on the one hand and altered PMCA and PLMTI activity on the other lends support to the underlying hypothesis that PMCA and PLMTI may be involved in the production of the anesthetic state. PMID:8890927

Horn, J L; Janicki, P K; Singh, G; Wamil, A W; Franks, J J

1996-01-01

47

Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2.  

PubMed

Mutations in the pantothenate kinase 2 (PANK2) gene have been identified in patients with neurodegeneration with brain iron accumulation (NBIA; formerly Hallervorden-Spatz disease). However, the mechanisms by which these mutations cause neurodegeneration are unclear, especially given the existence of multiple pantothenate kinase genes in humans and multiple PanK2 transcripts with potentially different subcellular localizations. We demonstrate that PanK2 protein is localized to mitochondria of neurons in human brain, distinguishing it from other pantothenate kinases that do not possess mitochondrial-targeting sequences. PanK2 protein translated from the most 5' start site is sequentially cleaved at two sites by the mitochondrial processing peptidase, generating a long-lived 48 kDa mature protein identical to that found in human brain extracts. The mature protein catalyzes the initial step in coenzyme A (CoA) synthesis but displays feedback inhibition in response to species of acyl CoA rather than CoA itself. Some, but not all disease-associated point mutations result in significantly reduced catalytic activity. The most common mutation, G521R, results in marked instability of the intermediate PanK2 isoform and reduced production of the mature isoform. These results suggest that NBIA is caused by altered neuronal mitochondrial lipid metabolism caused by mutations disrupting PanK2 protein levels and catalytic activity. PMID:15659606

Kotzbauer, Paul T; Truax, Adam C; Trojanowski, John Q; Lee, Virginia M-Y

2005-01-19

48

Alterations on Na(+),K (+)-ATPase and Acetylcholinesterase Activities Induced by Amyloid-? Peptide in Rat Brain and GM1 Ganglioside Neuroprotective Action.  

PubMed

Alzheimer's disease (AD) is a neurodegenerative disorder whose pathogenesis involves production and aggregation of amyloid-? peptide (A?). A?-induced toxicity is believed to involve alterations on as Na(+),K(+)-ATPase and acetylcholinesterase (AChE) activities, prior to neuronal death. Drugs able to prevent or to reverse these biochemical changes promote neuroprotection. GM1 is a ganglioside proposed to have neuroprotective roles in AD models, through mechanisms not yet fully understood. Therefore, this study aimed to investigate the effect of A?1-42 infusion and GM1 treatment on recognition memory and on Na(+),K(+)-ATPase and AChE activities, as well as, on antioxidant defense in the brain cortex and the hippocampus. For these purposes, Wistar rats received i.c.v. infusion of fibrilar A?1-42 (2 nmol) and/or GM1 (0.30 mg/kg). Behavioral and biochemical analyses were conducted 1 month after the infusion procedures. Our results showed that GM1 treatment prevented A?-induced cognitive deficit, corroborating its neuroprotective function. A? impaired Na(+),K(+)-ATPase and increase AChE activities in hippocampus and cortex, respectively. GM1, in turn, has partially prevented A?-induced alteration on Na(+),K(+)-ATPase, though with no impact on AChE activity. A? caused a decrease in antioxidant defense, specifically in hippocampus, an effect that was prevented by GM1 treatment. GM1, both in cortex and hippocampus, was able to increase antioxidant scavenge capacity. Our results suggest that A?-triggered cognitive deficit involves region-specific alterations on Na(+),K(+)-ATPase and AChE activities, and that GM1 neuroprotection involves modulation of Na(+),K(+)-ATPase, maybe by its antioxidant properties. Although extrapolation from animal findings is difficult, it is conceivable that GM1 could play an important role in AD treatment. PMID:24013887

Kreutz, Fernando; Scherer, Emilene B; Ferreira, Andréa G K; Petry, Fernanda Dos Santos; Pereira, Camila Lino; Santana, Fabiana; de Souza Wyse, Angela Terezinha; Salbego, Christianne Gazzana; Trindade, Vera Maria Treis

2013-09-08

49

Blockade of mGLUR5 receptors differentially alters amphetamine-induced enhancement of locomotor activity and of brain stimulation reward.  

PubMed

This study was aimed at determining the role of mGLUR5 glutamate receptors on amphetamine-induced enhancement of locomotion and of brain stimulation reward (BSR). The effect of different doses of the mGLUR5 antagonist, MPEP (0, 1, 3 and 9 mg/kg, i.p.), was assessed on reward induced by electrical stimulation of the lateral hypothalamus, and on the enhancement of reward by amphetamine (1 mg/kg, i.p.) in adult male Long Evans rats. The effect of a single dose of MPEP (0 and 9 mg/kg) on amphetamine-induced increase in locomotor activity was also assessed. Systemic injection of MPEP alone did not alter reward threshold and maximum rate of responding. Amphetamine produced a 25-30% decrease in reward threshold, an effect not altered by the highest dose of MPEP. At this dose, MPEP produced a weak inhibition of spontaneous locomotion and a significant attenuation of the enhanced locomotor activity induced by amphetamine. These findings show that mGLUR5 glutamate receptors are unlikely to constitute important elements of the reward-relevant pathway, and do not intervene in the enhancement effect of amphetamine. They also show, however, that these glutamate receptors play a key role in amphetamine-induced increased locomotor activity, providing additional evidence for a dissociation between the substrates that mediate these two behaviours. PMID:20498134

Gormley, Stéphanie; Rompré, Pierre-Paul

2010-05-24

50

Platelets Potentiate Brain Endothelial Alterations Induced by Plasmodium falciparum  

Microsoft Academic Search

Brain lesions of cerebral malaria (CM) are characterized by a sequestration of Plasmodium falciparum- parasitized red blood cells (PRBC) and platelets within brain microvessels, as well as by blood-brain barrier (BBB) disruption. In the present study, we evaluated the possibility that PRBC and platelets induce functional alterations in brain endothelium. In a human brain endothelial cell line, named HBEC-5i, exhibiting

Samuel C. Wassmer; Valery Combes; Francisco J. Candal; Irene Juhan-Vague; Georges E. Grau

2006-01-01

51

Alterations in brain protein kinase C after experimental brain injury  

Microsoft Academic Search

Regional activities and levels of protein kinase C were measured after lateral fluid percussion brain injury in rats. At 5 min and 20 min after injury, neither cofactor-dependent nor -independent PKC activities in the cytosol and membrane fractions changed in the injured and contralateral cortices or in the ipsilateral hippocampus. Western blot analysis revealed decreases in the levels of cytosolic

B. Padmaperurna; R. Mark; H. S. Dhillon; Mark P. Mattson; M. Renuka Prasad

1996-01-01

52

Working Memory Brain Activation Following Severe Traumatic Brain Injury  

Microsoft Academic Search

Functional magnetic resonance imaging (fMRI) has shown that brain activation during performance of working memory (WM) tasks under high memory loads is altered in adults with severe traumatic brain injury (TBI) relative to uninjured subjects (Perlstein et al., 2004; Scheibel et al., 2003). Our study attempted to equate TBI patients and orthopedically injured (OI) subjects on performance of an N-Back

Mary R. Newsome; Randall S. Scheibel; Joel L. Steinberg; Maya Troyanskaya; Rajkumar G. Sharma; Ronald A. Rauch; Xioaqi Li; Harvey S. Levin

2007-01-01

53

Benevolent sexism alters executive brain responses.  

PubMed

Benevolence is widespread in our societies. It is defined as considering a subordinate group nicely but condescendingly, that is, with charity. Deleterious consequences for the target have been reported in the literature. In this experiment, we used functional MRI (fMRI) to identify whether being the target of (sexist) benevolence induces changes in brain activity associated with a working memory task. Participants were confronted by benevolent, hostile, or neutral comments before and while performing a reading span test in an fMRI environment. fMRI data showed that brain regions associated previously with intrusive thought suppression (bilateral, dorsolateral, prefrontal, and anterior cingulate cortex) reacted specifically to benevolent sexism compared with hostile sexism and neutral conditions during the performance of the task. These findings indicate that, despite being subjectively positive, benevolence modifies task-related brain networks by recruiting supplementary areas likely to impede optimal cognitive performance. PMID:23660680

Dardenne, Benoit; Dumont, Muriel; Sarlet, Marie; Phillips, Christophe; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Salmon, Eric; Maquet, Pierre; Collette, Fabienne

2013-07-10

54

Chapter 2.3 Behavioral consequences of altered corticotropin-releasing factor activation in brain: a functionalist view of affective neuroscience  

Microsoft Academic Search

Organisms exposed to challenging stimuli that alter the status quo inside or outside of the body are required for survival purposes to generate appropriate coping responses which counteract the departure from homeostasis. Identification of an executive control mechanism within the brain capable of coordinating the multitude of endocrine, physiological and functional coping responses has high utility for discovery of efficacious

Stephen C. Heinrichs

2005-01-01

55

Alterations of Brain Activity Associated With Resolution of Emotional Distress and Pain in a Case of Severe Irritable Bowel Syndrome  

Microsoft Academic Search

Background & Aims: The association of psychosocial disturbances with more severe irritable bowel syndrome (IBS) is well recognized. However, there is no evidence as to how these associations might be mediated. Func- tional magnetic resonance imaging (fMRI) offers an op- portunity to study whether activation of the cingulate cortex, an area involved with the affective and pain intensity coding might

DOUGLAS A. DROSSMAN; YEHUDA RINGEL; BRENT A. VOGT; JANE LESERMAN; WEILI LIN; J. KEITH SMITH; WILLIAM WHITEHEAD

2003-01-01

56

Ipsilateral alterations in tryptophan hydroxylase activity in rat brain after hypothalamic 5,7-di-hydroxytryptamine lesion  

Microsoft Academic Search

The in vivo relationship between the amounts of tryptophan hydroxylase (TPH) protein and its intrinsic synthetic activity, measured by quantifying the amounts of ?-[3H]methyl-5-hydroxytryptamine (?-[3H]M5-HT), is reported in cell body and terminal areas of intact and disturbed serotonergic neurons following a unilateral 5,7-dihydroxytryptamine (5,7-DHT) lesion of the dorsolateral hypothalamus. Five days after the lesion, the relationships between TPH and its

Vesna Ljubi?-Thibal; Mirko Diksic; Edith Hamel; Sylvie Raison; Jean-François Pujol; Dinah Weissmann

1996-01-01

57

Age-related alteration of poly(ADP-ribose) polymerase activity in different parts of the brain  

Microsoft Academic Search

Poly(ADP-ribose) polymerase (PARP) is a conserved enzyme involved in the regula- tion of DNA repair and genome stability. The role of PARP during aging is not well known. In this study PARP activity was investigated in nuclear fractions from hippo- campus, cerebellum, and cerebral cortex of adult (4 months), old adult (14 months) and aged (24-27 months) rats. Concomitantly, the

Joanna B. Strosznajder; Robert P. Strosznajder

2000-01-01

58

The effects of loss versus alteration of consciousness on inhibition-related brain activity among individuals with a history of blast-related concussion  

Microsoft Academic Search

In this investigation, 27 individuals who experienced blast-related concussion, i.e., brief loss (LOC) or alteration (AOC) of consciousness, performed a stop task during functional magnetic resonance imaging. LOC versus AOC subjects displayed altered ventromedial prefrontal cortex activity, which correlated with somatic symptom severity-findings which may suggest a neural correlate of impaired self awareness after LOC.

Scott Matthews; Alan Simmons; Irina Strigo

2011-01-01

59

The effects of loss versus alteration of consciousness on inhibition-related brain activity among individuals with a history of blast-related concussion.  

PubMed

In this investigation, 27 individuals who experienced blast-related concussion, i.e., brief loss (LOC) or alteration (AOC) of consciousness, performed a stop task during functional magnetic resonance imaging. LOC versus AOC subjects displayed altered ventromedial prefrontal cortex activity, which correlated with somatic symptom severity-findings which may suggest a neural correlate of impaired self awareness after LOC. PMID:21144713

Matthews, Scott; Simmons, Alan; Strigo, Irina

2010-12-08

60

Mapping Structural Brain Alterations in Obsessive-Compulsive Disorder  

Microsoft Academic Search

Background: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. Objective: To describe the structural brain alterations detected in the magnetic resonance images of a large se- ries of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of vol- ume changes throughout the brain. Design: Case-control study. Setting: Referral OCD

Jesus Pujol; Carles Soriano-Mas; Pino Alonso; Narcõ ´ s Cardoner; Jose M. Menchon; Joan Deus; Julio Vallejo

2004-01-01

61

Altered functional brain networks in Prader-Willi syndrome  

PubMed Central

Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating.

Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L.; von Deneen, Karen M.; Zhou, Zhenyu; Gold, Mark S.; Liu, Yijun

2013-01-01

62

Altered functional brain networks in Prader-Willi syndrome.  

PubMed

Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating. PMID:23335390

Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L; von Deneen, Karen M; Zhou, Zhenyu; Gold, Mark S; Liu, Yijun

2013-01-21

63

Activity Responses to Altered Photoperiods.  

National Technical Information Service (NTIS)

Locomotor activity responses to altered photoperiods were investigated in male, Sprague-Dawley rats exposed to several types of artificial days. In each 24-hour period, each group of animals was exposed to different light:dark fluctuations without an alte...

E. L. Besch

1969-01-01

64

Intensive reasoning training alters patterns of brain connectivity at rest  

PubMed Central

Patterns of correlated activity among brain regions reflect functionally relevant networks that are widely assumed to be stable over time. We hypothesized that if these correlations reflect the prior history of co-activation of brain regions, then a marked shift in cognition could alter the strength of coupling between these regions. We sought to test whether intensive reasoning training in humans would result in tighter coupling among regions in the lateral fronto-parietal network, as measured with resting-state fMRI (rs-fMRI). Rather than designing an artificial training program, we studied individuals who were preparing for a standardized test that places heavy demands on relational reasoning, the Law School Admissions Test (LSAT). LSAT questions require test-takers to group or sequence items according to a set of complex rules. We recruited young adults who were enrolled in an LSAT course that offers 70 hours of reasoning instruction (n=25), and age- and IQ-matched controls intending to take the LSAT in the future (n=24). Rs-fMRI data were collected for all subjects during two scanning sessions separated by 90 days. An analysis of pairwise correlations between brain regions implicated in reasoning showed that fronto-parietal connections were strengthened, along with parietal-striatal connections. These findings provide strong evidence for neural plasticity at the level of large-scale networks supporting high-level cognition.

Mackey, Allyson P.; Miller Singley, Alison T.; Bunge, Silvia A.

2013-01-01

65

Transcranial magnetic stimulation induces alterations in brain monoamines  

Microsoft Academic Search

Summary Transcranial magnetic stimulation has been suggested as a possible therapeutic tool in depression. In behavioral models of depression, magnetic stimulation induced similar effects to those of electroconvulsive shock. This study demonstrates the effect of a single session of rapid TMS on tissue monoamines in rat brain. Alterations in monoamines were selective and specific in relation to brain areas and

D. Ben-Shachar; R. H. Belmaker; N. Grisaru; E. Klein

1997-01-01

66

Alterations in brain Protein Kinase A activity and reversal of morphine tolerance by two fragments of native Protein Kinase A inhibitor peptide (PKI)  

Microsoft Academic Search

Two peptide fragments of native Protein Kinase A inhibitor (PKI), PKI-(6-22)-amide and PKI-(Myr-14-22)-amide, significantly reversed low-level morphine antinociceptive tolerance in mice. The inhibition of Protein Kinase A (PKA) activity by both peptide fragments was then measured in specific brain regions (thalamus, periaqueductal gray (PAG), and medulla) and in lumbar spinal cord (LSC), which in previous studies have been shown to

George D. Dalton; Forrest L. Smith; Paul A. Smith; William L. Dewey

2005-01-01

67

Statistical parametric mapping reveals regional alterations in cannabinoid CB1 receptor distribution and G-protein activation in the 3D reconstructed epileptic rat brain  

PubMed Central

Summary Purpose The endocannabinoid system is known to modulate seizure activity in several in vivo and in vitro models, and CB1-receptor activation is anticonvulsant in the rat pilocarpine model of acquired epilepsy (AE). In these epileptic rats, a unique redistribution of the CB1 receptor occurs within the hippocampus; however, an anatomically inclusive analysis of the effect of status epilepticus (SE)–induced AE on CB1 receptors has not been thoroughly evaluated. Therefore, statistical parametric mapping (SPM), a whole-brain unbiased approach, was used to study the long-term effect of pilocarpine-induced SE on CB1-receptor binding and G-protein activation in rats with AE. Methods Serial coronal sections from control and epileptic rats were cut at equal intervals throughout the neuraxis and processed for [3H]WIN55,212-2 (WIN) autoradiography, WIN-stimulated [35S]GTP?S autoradiography, and CB1-receptor immunohistochemistry (IHC). The autoradiographic techniques were evaluated with both region of interest (ROI) and SPM analyses. Key Findings In rats with AE, regionally specific increases in CB1-receptor binding and activity were detected in cortex, discrete thalamic nuclei, and other regions including caudate-putamen and septum, and confirmed by IHC. However, CB1 receptors were unaltered in several brain regions, including substantia nigra and cerebellum, and did not exhibit regional decreases in rats with AE. Significance This study provides the first comprehensive evaluation of the regional distribution of changes in CB1-receptor expression, binding, and G-protein activation in the rat pilocarpine model of AE. These regions may ultimately serve as targets for cannabinomimetic compounds or manipulation of the endocannabinoid system in epileptic brain.

Sayers, Katherine W.; Nguyen, Peter T.; Blair, Robert E.; Sim-Selley, Laura J.; DeLorenzo, Robert J.

2013-01-01

68

Early Experience Alters Brain Function and Structure  

Microsoft Academic Search

Objective. To investigate the effects of early experience on brain function and structure. Methods. A randomized clinical trial tested the neu- rodevelopmental effectiveness of the Newborn Individ- ualized Developmental Care and Assessment Program (NIDCAP). Thirty preterm infants, 28 to 33 weeks' ges- tational age (GA) at birth and free of known develop- mental risk factors, participated in the trial. NIDCAP

Frank H. Duffy; Gloria B. McAnulty; Michael J. Rivkin; Sridhar Vajapeyam; Robert V. Mulkern; Simon K. Warfield; Petra S. Huppi; Samantha C. Butler; Nikk Conneman; Christine Fischer; Eric C. Eichenwald

2004-01-01

69

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain  

PubMed Central

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn2+ transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here.

Zhang, Xiaowei; Bearer, Elaine L.; Boulat, Benoit; Hall, F. Scott; Uhl, George R.; Jacobs, Russell E.

2010-01-01

70

Short-Term Exposure to Nickel Alters the Adult Rat Brain Antioxidant Status and the Activities of Crucial Membrane-Bound Enzymes: Neuroprotection by L-Cysteine  

Microsoft Academic Search

Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation)\\u000a and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of\\u000a short-term Ni-administration (as NiCl2, 13 mg\\/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE),\\u000a Na+,K+-ATPase, and Mg2+-ATPase;

Charis Liapi; Apostolos Zarros; Stamatios Theocharis; Konstantinos Voumvourakis; Foteini Anifantaki; Elena Gkrouzman; Zois Mellios; Nikolina Skandali; Hussam Al-Humadi; Stylianos Tsakiris

71

Altered brain reward circuits in eating disorders: chicken or egg?  

PubMed

The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. Our knowledge about the neurobiology of eating disorders is very limited, and the question remains whether alterations in brain structure or function in eating disorders are state related, remnants of the illness or premorbid traits. The brain reward system is a relatively well-characterized brain circuitry that plays a central role in the drive to eat and individuals with current or past eating disorders showed alterations in those pathways compared to controls. Here we propose that structural and functional alterations in the insula and frontal cortex, including orbitofrontal and cingulate regions, areas that contribute to reward and anxiety processing, could predispose to developing an eating disorder and that adaptive changes in those circuits in response to malnutrition or repeated binge eating and purging could further promote illness behavior, hinder recovery and contribute to relapse. PMID:23963630

Frank, Guido K W

2013-10-01

72

Altered brain tissue composition in heavy marijuana users  

Microsoft Academic Search

Marijuana is the most widely used illicit substance in the United States; however, previous imaging studies have not detected altered brain structure in marijuana users compared to non-users. Voxel-based morphometry was used to investigate possible differences in brain tissue composition in a group of 11 heavy marijuana users and a group of 8 non-users. All participants were male. Statistical comparisons

John A. Matochik; Dana A. Eldreth; Jean-Lud Cadet; Karen I. Bolla

2005-01-01

73

Iron Deficiency Alters Brain Development and Functioning 1,2  

Microsoft Academic Search

Iron deficiency anemia in early life is related to altered behavioral and neural development. Studies in human infants suggest that this is an irreversible effect that may be related to changes in chemistry of neuro- transmitters, organization and morphology of neuronal networks, and neurobiology of myelination. The acquisition of iron by the brain is an age-related and brain-region-dependent process with

John Beard

74

Predicting intrinsic brain activity.  

PubMed

Multivariate supervised learning methods exhibit a remarkable ability to decode externally driven sensory, behavioral, and cognitive states from functional neuroimaging data. Although they are typically applied to task-based analyses, supervised learning methods are equally applicable to intrinsic effective and functional connectivity analyses. The obtained models of connectivity incorporate the multivariate interactions between all brain regions simultaneously, which will result in a more accurate representation of the connectome than the ones available with standard bivariate methods. Additionally the models can be applied to decode or predict the time series of intrinsic brain activity of a region from an independent dataset. The obtained prediction accuracy provides a measure of the integration between a brain region and other regions in its network, as well as a method for evaluating acquisition and preprocessing pipelines for resting state fMRI data. This article describes a method for learning multivariate models of connectivity. The method is applied in the non-parametric prediction accuracy, influence, and reproducibility-resampling (NPAIRS) framework, to study the regional variation of prediction accuracy and reproducibility (Strother et al., 2002). The resulting spatial distribution of these metrics is consistent with the functional hierarchy proposed by Mesulam (1998). Additionally we illustrate the utility of the multivariate regression connectivity modeling method for optimizing experimental parameters and assessing the quality of functional neuroimaging data. PMID:23707580

Craddock, R Cameron; Milham, Michael P; Laconte, Stephen M

2013-05-24

75

Activation of the Stress Axis and Neurochemical Alterations in Specific Brain Areas by Concentrated Ambient Particle Exposure with Concomitant Allergic Airway Disease  

PubMed Central

Objective Exposure to ambient particulate matter (PM) has been linked to respiratory diseases in people living in urban communities. The mechanism by which PM produces these diseases is not clear. We hypothesized that PM could act on the brain directly to stimulate the stress axis and predispose individuals to these diseases. The purpose of this study was to test if exposure to PM can affect brain areas involved in the regulation of neuroendocrine functions, especially the stress axis, and to study whether the presence of preexisting allergic airway disease aggravates the stress response. Design Adult male rats (n = 8/group) with or without ovalbumin (OVA)-induced allergic airway disease were exposed to concentrated air particles containing PM with an aerodynamic diameter ? 2.5 ?m (PM2.5) for 8 hr, generated from ambient air in an urban Grand Rapids, Michigan, community using a mobile air research laboratory (AirCARE 1). Control animals were exposed to normal air and were treated with saline. Measurements A day after PM2.5 exposure, animals were sacrificed and the brains were removed, frozen, and sectioned. The paraventricular nucleus (PVN) and other brain nuclei were micro-dissected, and the concentrations of aminergic neurotransmitters and their metabolites were measured using high-performance liquid chromatography with electrochemical detection. Serum corticosterone levels were measured using radioimmunoassay. Results A significant increase in the concentration (mean ± SE, pg/?g protein) of norepinephrine in the PVN was produced by exposure to concentrated ambient particles (CAPs) or OVA alone (12.45 ± 2.7 and 15.84 ± 2.8, respectively) or after sensitization with OVA (19.06 ± 3.8) compared with controls (7.98 ± 1.3; p < 0.05). Serum corticosterone (mean ± SE, ng/mL) was significantly elevated in the OVA + CAPs group (242.786 ± 33.315) and in the OVA-presensitized group (242.786 ± 33.315) compared with CAP exposure alone (114.55 ± 20.9). Exposure to CAPs (alone or in combination with OVA pretreatment) can activate the stress axis, and this could probably play a role in aggravating allergic airway disease.

Sirivelu, Madhu P.; MohanKumar, Sheba M.J.; Wagner, James G.; Harkema, Jack R.; MohanKumar, Puliyur S.

2006-01-01

76

Behavioural alteration in chronic pain: Are brain glia involved?  

Microsoft Academic Search

Behavioural symptoms such as abnormal emotionality (including anxious and depressive episodes) and cognition (for instance weakened decision-making) are highly frequent in both chronic pain patients and their animal models. The theory developed in the present article posits that alterations in glial cells (astrocytes and microglia) in cortical and limbic brain regions might be the origin of such emotional and cognitive

T. Panigada; R.-D. Gosselin

2011-01-01

77

Brain alterations in the classical form of congenital muscular dystrophy  

Microsoft Academic Search

In the classical form of congenital muscular dystrophy (CMD), subclinical brain involvement is frequent. In order to establish the natural evolution of CNS alterations in this type of CMD, the cerebral functions of 12 cases were examined longitudinally for a mean period of 8 years. There were 7 boys and 5 girls, with a mean age of 5 years at

Carlo P. Trevisan; Francesco Martinello; Emilia Ferruzza; Marina Fanin; Martine Chevallay; Fernando M. S. Tomé

1996-01-01

78

[Chronic pain alters the structure of the brain].  

PubMed

Local morphologic alterations of the brain in areas ascribable to the transmission of pain were recently detected in patients suffering from phantom pain, chronic back pain, irritable bowl syndrome, fibromyalgia and frequent headaches. These alterations were different for each pain syndrome, but overlapped in the cingulate cortex, the orbit frontal cortex, the insula and dorsal pons. As it seems that chronic pain patients have a common "brain signature" in areas known to be involved in pain regulation, the question arises whether these changes are the cause or the consequence of chronic pain. The in vivo demonstration of a loss of brain gray matter in patients suffering from chronic pain compared to age and sex-matched healthy controls could represent the heavily discussed neuroanatomical substrate for pain memory. PMID:19838741

May, A

2009-12-01

79

Mice lacking brain/kidney phosphate-activated glutaminase (GLS1) have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth  

PubMed Central

Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated and died in the first post-natal day. No gross or microscopic defects were detected in peripheral organs or in the central nervous system. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activity-dependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the Pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that while alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and so the mutation is associated with impaired respiratory function, abnormal goal-directed behavior and neonatal demise.

Masson, Justine; Darmon, Michele; Conjard, Agnes; Chuhma, Nao; Ropert, Nicole; Thoby-Brisson, Muriel; Foutz, Arthur S.; Parrot, Sandrine; Miller, Gretchen M.; Jorisch, Renee; Polan, Jonathan; Hamon, Michel; Hen, Rene; Rayport, Stephen

2009-01-01

80

Blood-brain barrier alterations in ageing and dementia.  

PubMed

The current pathogenic scenarios of different types of dementia are based on a number of common mechanisms of neurodegeneration, such as accumulation of abnormal proteins (within or outside cells), mitochondrial dysfunction and oxidative stress, calcium homeostasis dysregulation, early synaptic disconnection and late apoptotic cell death. Ageing itself is associated with mild cognitive deterioration, probably due to subtle multifactorial changes resulting in a global decrease of a functional brain reserve. Increased age is a risk factor for neurodegeneration and key pathological features of dementia can also be found in aged brains. One of the underexplored brain structures in ageing and dementia is the blood-brain barrier (BBB), a complex cellular gate which regulates tightly the transport of molecules into and from the central nervous system. Disruption of this barrier is now increasingly documented not only in brain vascular disease but also in ageing and neurodegenerative disorders. To date, such evidence points mainly at an association between various dementia forms and disruption of the BBB. But, in reviewing such results, and taking into account the exquisite sensitivity of neuronal function to the composition of the interstitial brain fluid (IBF), which is regulated by the BBB, we would like to propose the existence of a possible causal link between alterations of BBB and conditions associated with cognitive decline. PMID:19264328

Popescu, Bogdan O; Toescu, Emil C; Popescu, Lauren?iu M; Bajenaru, Ovidiu; Muresanu, Dafin F; Schultzberg, Marianne; Bogdanovic, Nenad

2009-03-04

81

Alterations in physiologic functions and in brain monoamine content in streptozocin-diabetic rats.  

PubMed

In the present study, we used streptozocin (STZ) to induce diabetes in rats and observed alterations in several physiologic functions and in monoamine content of different brain regions. Rats with STZ diabetes displayed a thermoregulatory deficit in the cold. Both the body temperature and metabolic rate of the diabetic animals were reduced at ambient temperatures below 22 degrees C. These diabetic animals had a higher level of the spontaneous pain threshold, but displayed a reduced sensitivity of analgesic responses to morphine injection. In addition, these diabetic animals had a lower level of spontaneous motor activity, but displayed an increased sensitivity of locomotor stimulant responses to amphetamine administration. Biochemical examination revealed that the diabetic animals had a lower serotonin level in both the hypothalamus and the brainstem without changes in the serotonin levels of the corpus striatum. These diabetic animals also had a lower catecholamine level in the hypothalamus, but a higher catecholamine level in the corpus striatum. The alterations in brain monoamine content and in the above-mentioned physiologic parameters were reversed after insulin replacement therapy. The data suggest that alterations in various autonomic, somatosensory, and motor neural functions of untreated STZ-diabetic rats correlated with a reproducible pattern of monoamine content in various brain regions (a pattern that differed from that observed in healthy control rats), and that both the altered neural function and the altered brain monoamine pattern were reversed after insulin therapy. PMID:3514326

Chu, P C; Lin, M T; Shian, L R; Leu, S Y

1986-04-01

82

Late brain alterations in sepsis-survivor rats.  

PubMed

Central nervous system (CNS) dysfunction secondary to sepsis is characterized by long-term cognitive impairment. It was observed that oxidative damage, energetic metabolism impairment, and cytokine level alteration seen in early times in an animal model of sepsis may persist for up to 10 days and might be associated with cognitive damage. In order to understand these mechanisms, at least in part, we evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF), oxidative parameters, and energetic metabolism in the brain of rats at both 30 and 60 days after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with "basic support" or were sham-operated. Both 30 and 60 days after surgery, the CSF was collected and the animals were killed by decapitation. Then, the prefrontal cortex, hippocampus, striatum, and cortex were collected. Thirty days after surgery, an increase of IL-6 level in the CSF; an increase in the thiobarbituric acid-reactive species (TBARS) in prefrontal cortex and a decrease in hippocampus, striatum, and cortex; a decrease of carbonyl protein formation only in prefrontal cortex and an increase in striatum; and an increase in the complex IV activity only in hippocampus were observed. Sixty days after sepsis, an increase of TNF-? level in the CSF; a decrease of TBARS only in hippocampus; an increase of carbonyl protein formation in striatum; and a decrease of complex I activity in prefrontal cortex, hippocampus, and striatum were observed. These findings may contribute to understanding the role of late cognitive impairment. Further studies may address how these findings interact during sepsis development and contribute to CNS dysfunction. Synapse 67:786-793, 2013. © 2013 Wiley Periodicals, Inc. PMID:23740866

Steckert, Amanda V; Comim, Clarissa M; Mina, Francielle; Mendonça, Bruna P; Dominguini, Diogo; Ferreira, Gabriela K; Carvalho-Silva, Milena; Vieira, Júlia S; Streck, Emilio L; Quevedo, João; Dal-Pizzol, Felipe

2013-07-04

83

Behavioural alteration in chronic pain: are brain glia involved?  

PubMed

Behavioural symptoms such as abnormal emotionality (including anxious and depressive episodes) and cognition (for instance weakened decision-making) are highly frequent in both chronic pain patients and their animal models. The theory developed in the present article posits that alterations in glial cells (astrocytes and microglia) in cortical and limbic brain regions might be the origin of such emotional and cognitive chronic pain-associated impairments. Indeed, in mood disorders (unipolar depression, anxiety disorders, autism or schizophrenia) glial changes in brain regions involved in mood control (prefrontal and cingulate cortices, amygdala and the hippocampus) have been recurrently described. Besides, glial cells have been undoubtedly identified as key actors in the sensory component of chronic pain, owing to the profound phenotypical changes they undergo throughout the sensory pathway. Hence, the possibility arises that brain astrocytes and microglia react in upper brain structures as well, mediating the related mood and cognitive dysfunctions in chronic pain. So far, only very few studies have provided results in this prospect, mainly indirectly in pain-independent researches. Nevertheless, the first scant available data seem to merge in a unified description of a brain glial reaction occurring after chronic peripheral lesion. The present article uses this scarce literature to formulate the provocative theory of a glia-driven mood and cognitive dysfunction in chronic pain, expounding upon its validity and putative therapeutical impact as well as its current limitations and expected future developments. PMID:21741179

Panigada, T; Gosselin, R-D

2011-07-07

84

Brain Gym. Simple Activities for Whole Brain Learning.  

ERIC Educational Resources Information Center

|This booklet contains simple movements and activities that are used with students in Educational Kinesiology to enhance their experience of whole brain learning. Whole brain learning through movement repatterning and Brain Gym activities enable students to access those parts of the brain previously unavailable to them. These movements of body and…

Dennison, Paul E.; Dennison, Gail E.

85

Repeated swim stress alters brain benzodiazepine receptors measured in vivo  

SciTech Connect

The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

1989-06-01

86

Fetal Dexamethasone Exposure Affects Basal Ornithine Decarboxylase Activity in Developing Rat Brain Regions and Alters Acute Responses to Hypoxia and Maternal Separation  

Microsoft Academic Search

Although glucocorticoids are widely used to stimulate fetal\\/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg\\/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions.

R. Q. Carlos; F. J. Seidler; S. E. Lappi; T. A. Slotkin

1991-01-01

87

Topographic Mapping of Brain Activity.  

National Technical Information Service (NTIS)

The general purpose of this research was to relate topographical mapping of brain electrical activity to performance on several tasks with different cognitive demands. A total of 35 subjects were studied. Fifteen subjects participated in a linguistic cogn...

E. S. Barrett G. F. Wilson

1987-01-01

88

Quantification of functional alterations after in vitro traumatic brain injury.  

PubMed

Traumatic brain injury (TBI) is caused by mechanical forces, producing tissue deformation at the moment of injury. Complex cellular, neurochemical and metabolic alterations are initiated by the deformation and result in delayed cell death and dysfunction. Using an in vitro model of TBI based on organotypic brain slice cultures, we have quantitatively studied the relationship between tissue deformation and functional outcome. Specifically, we studied the effects of low levels of tissue deformation on the functional outcomes as measured by electrophysiology recordings. In response to 5% and 10% biaxial Lagrangian strain, the maximal evoked response and the excitability of neural networks were found to be decreased. Additionally, the different anatomic subregions of the hippocampus displayed different levels of impairment to the injuries. These results suggest that the network function was affected by low levels of applied strain which induced minimal cell death in previous studies. PMID:19963487

Yu, Zhe; Elkin, Benjamin S; Morrison, Barclay

2009-01-01

89

Alterations of excitatory amino acid receptors in the brain of managese-treated mice  

Microsoft Academic Search

An excessive activation of excitatory amino acid (EAA) receptors has been associated with oxidative stress, which is considered\\u000a the primary cause of manganese (Mn) poisoning neurotoxicity. Therefore, the EAA receptor distribution was analyzed by autoradiographic\\u000a methods in several brain regions during Mn intoxication. We found that chronic treatment of mice with MnCl2 during 8 wk significantly alters thel-[3H]glutamate (l-[3H]Glu) binding

Georgina Cano; Heberto Suárez-Roca; Ernesto Bonilla

1997-01-01

90

Antenatal Maternal Stress Alters Functional Brain Responses In Adult Offspring During Conditioned Fear  

PubMed Central

Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility (‘freezing’). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation.

Sadler, Theodore R.; Nguyen, Peter T.; Yang, Jun; Givrad, Tina K.; Mayer, Emeran A.; Maarek, Jean-Michel I.; Hinton, David R.; Holschneider, Daniel P.

2011-01-01

91

Antenatal maternal stress alters functional brain responses in adult offspring during conditioned fear.  

PubMed

Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the ((14))C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility ("freezing"). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, and nucleus accumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation. PMID:21300034

Sadler, Theodore R; Nguyen, Peter T; Yang, Jun; Givrad, Tina K; Mayer, Emeran A; Maarek, Jean-Michel I; Hinton, David R; Holschneider, Daniel P

2011-04-18

92

Activated oxygen alters cerebral microvascular responses in newborn pigs  

SciTech Connect

In piglets, cerebral ischemia/reperfusion blocks prostanoid dependent cerebral vasodilation to hypercapnia (CO{sub 2}) and hypotension but not prostanoid independent dilation to isoproterenol (Isu) or constriction to norepinephrine (NE). Ischemia/reperfusion increases activated-O{sub 2} production by piglet brains. Using cranial windows in piglets, the authors investigated the hypothesis that activated oxygen can block prostanoid dependent cerebral vasodilator responses to CO{sub 2} and hypotension without altering responses to Isu and NE. Exposure to an activated oxygen generating system of xanthine oxidase, hypoxanthine, and Fe that made about 3 times the activated-O{sub 2} on the brain surface as ischemia/reperfusion caused reversible pial arteriolar dilation. After exposure, pial arteriolar dilation was reduced to CO{sub 2} and hypotension but not to Isu. NE constrictor responses were also unaltered. H{sub 2}O{sub 2} or H{sub 2}O{sub 2} + Fe caused constriction followed by reversible dilation. After exposure, pial arteriolar dilation in response to CO{sub 2} and hypotension was not altered. However, addition of xanthine oxidase and hypoxanthine with H{sub 2}O{sub 2} and Fe totally eliminated pial arteriolar dilator responses to CO{sub 2} and hypotension but did not decrease dilation caused by Isu or constriction caused by NE. The authors conclude that activated oxygen could produce the altered prostanoid dependent pial arteriolar responses observed following ischemia in piglets.

Leffler, C.W.; Busiia, D.W.; Armstead, W.M.; Mirro, R.; Thelin, O. (Univ. of Tennessee, Memphis (United States))

1990-02-26

93

Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain  

Microsoft Academic Search

Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic-pituitary-adrenal (HPA) axis activity. We investigated the effects of chronic 21 day isolation of Wistar rats on the extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine

Miroslav Adzic; Jelena Djordjevic; Ana Djordjevic; Ana Niciforovic; Constantinos Demonacos; Marija Radojcic; Marija Krstic-Demonacos

2009-01-01

94

Age-related alteration of activity and gene expression of endothelial nitric oxide synthase in different parts of the brain in rats  

Microsoft Academic Search

Nitric oxide (NO) plays important roles in aging and neurodegeneration. Our previous results indicated that aging differently affects NOS isoforms. Expression of nNOS mRNA was lower while iNOS was absent at any age. However, total NO synthesis increased in aged cerebral cortex and cerebellum as a consequence of changes of nNOS phosphorylation state. The question arise how aging influences activity

Joanna B. Strosznajder; Henryk J??ko; Agata Zambrzycka; Anne Eckert; Ma?gorzata Chalimoniuk

2004-01-01

95

Activation and alteration of lysosomes in multiple system atrophy.  

PubMed

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder. Its histopathological features include glial cytoplasmic inclusions that contain ?-synuclein as the main component. Recently, multiple lines of evidence have suggested a role for lysosomes in the pathogenesis of many neurodegenerative diseases. To elucidate whether lysosomes are also implicated in the pathology of MSA, we carried out an immunohistochemical study using antibodies against lysosomal proteins in the brains of patients with MSA and in control brains. A robust increase in the expression and an alteration in the morphology and distribution of lysosomal-protein-positive structures were observed in MSA brains. Double immunohistochemistry demonstrated that lysosomal markers did not colocalize mainly with glial cytoplasmic inclusions, but colocalized with a microglial marker. These immunohistochemical signatures suggest that lysosomes are activated in microglia during the disease process, and play a pivotal role in the pathology of MSA. PMID:22343695

Makioka, Kouki; Yamazaki, Tsuneo; Takatama, Masamitsu; Nakazato, Yoichi; Okamoto, Koichi

2012-03-28

96

Prion disease induced alterations in gene expression in spleen and brain prior to clinical symptoms  

PubMed Central

Prion diseases are fatal neurodegenerative disorders that affect animals and humans. There is a need to gain understanding of prion disease pathogenesis and to develop diagnostic assays to detect prion diseases prior to the onset of clinical symptoms. The goal of this study was to identify genes that show altered expression early in the disease process in the spleen and brain of prion disease-infected mice. Using Affymetrix microarrays, we identified 67 genes that showed increased expression in the brains of prion disease-infected mice prior to the onset of clinical symptoms. These genes function in many cellular processes including immunity, the endosome/lysosome system, hormone activity, and the cytoskeleton. We confirmed a subset of these gene expression alterations using other methods and determined the time course in which these changes occur. We also identified 14 genes showing altered expression prior to the onset of clinical symptoms in spleens of prion disease infected mice. Interestingly, four genes, Atp1b1, Gh, Anp32a, and Grn, were altered at the very early time of 46 days post-infection. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as surrogate markers for the early detection and diagnosis of prion disease.

Kim, Hyeon O; Snyder, Greg P; Blazey, Tyler M; Race, Richard E; Chesebro, Bruce; Skinner, Pamela J

2008-01-01

97

Conscious Intention and Brain Activity  

Microsoft Academic Search

The problem of free will lies at the heart of modern scientific studies of consciousness. An influential series of experiments by Libet has suggested that conscious intentions arise as a result of brain activity. This contrasts with tradi- tional concepts of free will, in which the mind controls the body. A more recent study by Haggard and Eimer has further

Patrick Haggard

2001-01-01

98

Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties.  

PubMed

Chronic alcohol consumption causes numerous biochemical and biophysical changes in the central nervous system, in which mitochondria is the primary organelle affected. In the present study, we hypothesized that alcohol alters the mitochondrial membrane properties and leads to mitochondrial dysfunction via mitochondrial reactive oxygen species (mROS) and reactive nitrogen species (RNS). Alcohol-induced hypoxia further enhances these effects. Administration of alcohol to rats significantly increased the mitochondrial lipid peroxidation and protein oxidation with decreased SOD2 mRNA and protein expression was decreased, while nitric oxide (NO) levels and expression of iNOS and nNOS in brain cortex were increased. In addition, alcohol augmented HIF-1? mRNA and protein expression in the brain cortex. Results from this study showed that alcohol administration to rats decreased mitochondrial complex I, III, IV activities, Na(+)/K(+)-ATPase activity and cardiolipin content with increased anisotropic value. Cardiolipin regulates numerous enzyme activities, especially those related to oxidative phosphorylation and coupled respiration. In the present study, decreased cardiolipin could be ascribed to ROS/RNS-induced damage. In conclusion, alcohol-induced ROS/RNS is responsible for the altered mitochondrial membrane properties, and alcohol-induced hypoxia further enhance these alterations, which ultimately leads to mitochondrial dysfunction. PMID:23212448

Reddy, Vaddi Damodara; Padmavathi, Pannuru; Kavitha, Godugu; Saradamma, Bulle; Varadacharyulu, Nallanchakravarthula

2012-12-01

99

NFL Veterans Show 'Abnormalities' in Brain Activity  

MedlinePLUS

... please enable JavaScript. NFL Veterans Show 'Abnormalities' in Brain Activity: Study Ex-players who had been sent ... researchers say they see unusual activity in the brains of former National Football League players. These traits ...

100

Alteration and Reorganization of Functional Networks: A New Perspective in Brain Injury Study  

PubMed Central

Plasticity is the mechanism underlying the brain’s potential capability to compensate injury. Recently several studies have shown how functional connections among the brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various areas of the brain and it could be an essential tool for brain functional studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives, and clinical uses in brain injury studies.

Castellanos, Nazareth P.; Bajo, Ricardo; Cuesta, Pablo; Villacorta-Atienza, Jose Antonio; Paul, Nuria; Garcia-Prieto, Juan; del-Pozo, Francisco; Maestu, Fernando

2011-01-01

101

Alteration of blood-brain barrier function by methamphetamine and cocaine  

Microsoft Academic Search

The integrity of the blood-brain barrier (BBB) plays an important role in maintaining a safe neural microenvironment in the\\u000a brain. Loss of BBB integrity has been recognized as a major cause of profound brain alterations. Psychoactive drugs such as\\u000a methamphetamine (METH) or cocaine are well-known drugs of abuse that can alter the permeability of the BBB via various mechanisms.\\u000a In

J. B. Dietrich

2009-01-01

102

Alteration of zinc concentrations in the brain implanted with C6 glioma  

Microsoft Academic Search

The uptake of zinc, an essential element, is critical not only for cell proliferation but also cell functions. On the basis of the evidence suggesting that preferential uptake of 65Zn in brain tumors may be associated with avid cell proliferation, alteration of zinc concentrations in the brain implanted with C6 glioma was studied by brain autoradiography using 65Zn. After implantation

Atsushi Takeda; Haruna Tamano; Naoto Oku

2003-01-01

103

Electroencephalographic Power and Coherence Analyses Suggest Altered Brain Function in Abstinent Male Heroin-Dependent Patients  

Microsoft Academic Search

Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic (EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In the present study, we compared EEG power and coherence measures of 18 abstinent heroin-dependent subjects with those of

Ingmar H. A. Franken; Cornelis J. Stam; Vincent M. Hendriks; Wim van den Brink

2004-01-01

104

Altered pattern of brain dopamine synthesis in male adolescents with attention deficit hyperactivity disorder  

PubMed Central

Background Limited data from positron emission tomography (PET) studies of subjects with attention-deficit/hyperactivity disorder (ADHD) indicate alterations in brain dopamine neurotransmission. However, these studies have used conventional univariate approaches that are less sensitive to detect complex interactions that may exist between different brain dopamine pathways and individual symptoms of ADHD. We aimed to investigate these potential interactions in adolescents with ADHD. Methods We used a 3D PET scan to measure utilization of native L-[11C]-DOPA to map dopamine presynaptic function in various cortical, striatal and midbrain regions in a group of 8 male adolescents with ADHD and 6 age matched controls. To evaluate the interactions between the studied brain regions, multivariate statistical methods were used. Results Abnormal dopaminergic function was found in multiple brain regions of patients with ADHD. A main finding was lower L-[11C]-DOPA utilization in adolescent with ADHD as compared to control subjects, especially in subcortical regions. This pattern of dopaminergic activity was correlated specifically with symptoms of inattention. Conclusion Dopamine signalling in the brain plays an important modulatory role in a variety of motor and cognitive functions. We have identified region-specific functional abnormalities in dopaminergic function, which may help better account for the symptoms of ADHD.

Forssberg, Hans; Fernell, Elisabeth; Waters, Susanna; Waters, Nicholas; Tedroff, Joakim

2006-01-01

105

Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes.  

PubMed

The neurosteroid 3alpha-hydroxysteroid-5alpha-pregnan-20-one (allopregnanolone) acts as a positive allosteric modulator of gamma-aminobutyric acid at gamma-aminobutyric acid type A receptors and hence is a powerful anxiolytic, anticonvulsant, and anesthetic agent. Allopregnanolone is synthesized from progesterone by reduction to 5alpha-dihydroprogesterone, mediated by 5alpha-reductase, and by reduction to allopregnanolone, mediated by 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Previous reports suggested that some selective serotonin reuptake inhibitors (SSRIs) could alter concentrations of allopregnanolone in human cerebral spinal fluid and in rat brain sections. We determined whether SSRIs directly altered the activities of either 5alpha-reductase or 3alpha-HSD, using an in vitro system containing purified recombinant proteins. Although rats appear to express a single 3alpha-HSD isoform, the human brain contains several isoforms of this enzyme, including a new isoform we cloned from human fetal brains. Our results indicate that the SSRIs fluoxetine, sertraline, and paroxetine decrease the K(m) of the conversion of 5alpha-dihydroprogesterone to allopregnanolone by human 3alpha-HSD type III 10- to 30-fold. Only sertraline inhibited the reverse oxidative reaction. SSRIs also affected conversions of androgens to 3alpha- and 3alpha, 17beta-reduced or -oxidized androgens mediated by 3alpha-HSD type II(Brain). Another antidepressant, imipramine, was without any effect on allopregnanolone or androstanediol production. The region-specific expression of 3alpha-HSD type II(Brain) and 3alpha-HSD type III mRNAs suggest that SSRIs will affect neurosteroid production in a region-specific manner. Our results may thus help explain the rapid alleviation of the anxiety and dysphoria associated with late luteal phase dysphoria disorder and major unipolar depression by these SSRIs. PMID:10557352

Griffin, L D; Mellon, S H

1999-11-01

106

Extrinsic Embryonic Sensory Stimulation Alters Multimodal Behavior and Cellular Activation  

PubMed Central

Embryonic vision is generated and maintained by spontaneous neuronal activation patterns, yet extrinsic stimulation also sculpts sensory development. Because the sensory and motor systems are interconnected in embryogenesis, how extrinsic sensory activation guides multimodal differentiation is an important topic. Further, it is unknown whether extrinsic stimulation experienced near sensory sensitivity onset contributes to persistent brain changes, ultimately affecting postnatal behavior. To determine the effects of extrinsic stimulation on multimodal development, we delivered auditory stimulation to bobwhite quail groups during early, middle, or late embryogenesis, and then tested postnatal behavioral responsiveness to auditory or visual cues. Auditory preference tendencies were more consistently toward the conspecific stimulus for animals stimulated during late embryogenesis. Groups stimulated during middle or late embryogenesis showed altered postnatal species-typical visual responsiveness, demonstrating a persistent multimodal effect. We also examined whether auditory-related brain regions are receptive to extrinsic input during middle embryogenesis by measuring postnatal cellular activation. Stimulated birds showed a greater number of ZENK-immunopositive cells per unit volume of brain tissue in deep optic tectum, a midbrain region strongly implicated in multimodal function. We observed similar results in the medial and caudomedial nidopallia in the telencephalon. There were no ZENK differences between groups in inferior colliculus or in caudolateral nidopallium, avian analog to prefrontal cortex. To our knowledge, these are the first results linking extrinsic stimulation delivered so early in embryogenesis to changes in postnatal multimodal behavior and cellular activation. The potential role of competitive interactions between the sensory and motor systems is discussed.

Markham, Rebecca G.; Shimizu, Toru; Lickliter, Robert

2009-01-01

107

Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.  

PubMed

Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions. PMID:11738545

Lehmann, D; Faber, P L; Achermann, P; Jeanmonod, D; Gianotti, L R; Pizzagalli, D

2001-11-30

108

Perinatal risk factors altering regional brain structure in the preterm infant  

Microsoft Academic Search

Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of

Deanne K. Thompson; Simon K. Warfield; John B. Carlin; Masa Pavlovic; Hong X. Wang; Merilyn Bear; Michael J. Kean; Lex W. Doyle; Gary F. Egan; Terrie E. Inder

2007-01-01

109

Alteration and reorganization of functional networks: a new perspective in brain injury study.  

PubMed

Plasticity is the mechanism underlying the brain's potential capability to compensate injury. Recently several studies have shown how functional connections among the brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various areas of the brain and it could be an essential tool for brain functional studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives, and clinical uses in brain injury studies. PMID:21960965

Castellanos, Nazareth P; Bajo, Ricardo; Cuesta, Pablo; Villacorta-Atienza, José Antonio; Paúl, Nuria; Garcia-Prieto, Juan; Del-Pozo, Francisco; Maestú, Fernando

2011-09-21

110

Mechanisms of Microwave-Induced Blood-Brain Barrier Alterations.  

National Technical Information Service (NTIS)

This investigation was designed to study the mechanisms of interaction between microwaves and the blood-brain barrier and was aimed at correlating changes of blood-brain barrier permeability with the quantity and distribution of absorbed microwave energy ...

J. C. Lin

1980-01-01

111

Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models*  

PubMed Central

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in HdhQ111/+ mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool.

Mochel, Fanny; Durant, Brandon; Meng, Xingli; O'Callaghan, James; Yu, Hua; Brouillet, Emmanuel; Wheeler, Vanessa C.; Humbert, Sandrine; Schiffmann, Raphael; Durr, Alexandra

2012-01-01

112

Right Brain Activities to Improve Analytical Thinking.  

ERIC Educational Resources Information Center

Schools tend to have a built-in bias toward left brain activities (tasks that are linear and sequential in nature), so the introduction of right brain activities (functions related to music, rhythm, images, color, imagination, daydreaming, dimensions) brings a balance into the classroom and helps those students who may be right brain oriented. To…

Lynch, Marion E.

113

Melatonin stimulates brain glutathione peroxidase activity  

Microsoft Academic Search

Exogenously administered melatonin causes a 2-fold rise in glutathione peroxidase activity within 30 min in the brain of the rat. Furthermore, brain glutathione peroxidase activity is higher at night than during the day and is correlated with high night-time tissue melatonin levels. Glutathione peroxidase is thought to be the principal enzyme eliminating peroxides in the brain. This antioxidative enzyme reduces

L. R. Barlow-Walden; R. J. Reiter; M. Abe; M. Pablos; A. Menendez-Pelaez; L.-D. Chen; B. Poeggeler

1995-01-01

114

Alteration of Blood-Brain Barrier Integrity by Retroviral Infection  

PubMed Central

The blood–brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans), both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies.

Afonso, Philippe V.; Ozden, Simona; Cumont, Marie-Christine; Seilhean, Danielle; Cartier, Luis; Rezaie, Payam; Mason, Sarah; Lambert, Sophie; Huerre, Michel; Gessain, Antoine; Couraud, Pierre-Olivier; Pique, Claudine

2008-01-01

115

Alterations of metallothionein isomers in Hg(0)-exposed rat brain.  

PubMed

Previously we found that exposure to mercury vapor effectively induced brain metallothionein (MT) in rats. Here, using FPLC-gel chromatography, we examined time-dependent alterations in the MT isomers, MT-I/II and MT-III, following 3 weeks of exposure. Rats were exposed to mercury vapor at 8.3 mg/m3 for 15 h in total over 5 consecutive days. Total MT levels in rat cerebrum and cerebellum increased by 65% and 155%, respectively, 24 h after the final exposure. The increased levels in both tissues remained unchanged for at least 2 weeks after termination of exposure. Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10%. Through mercury vapor exposure, MT-I/II was quickly induced to a significant extent in both tissues, reaching a level comparable to that of MT-III. The induction rate of MT-I/II in the cerebellum was somewhat higher than in the cerebrum. Chromatograms showed that the MT-I/II thus induced began to decline at an early stage in both tissues. In the cerebrum, the amount of MT-I/II on day 22 was about 30% of the maximum level on day 1. On the other hand, the induction of MT-III was not that dramatic, but it did become evident, at least in the latter stage, when MT-I/II had begun to decrease. Thus, though the induction rate of MT-III was not as high as MT-I/II, it was sustained throughout the experimental period. PMID:12491035

Yasutake, A; Nagano, M; Hirayama, K

2002-11-01

116

Scale-similar activity in the brain  

Microsoft Academic Search

The spectral analysis of multichannel magnetoencephalographic data is presented. This analysis revealed a local similarity regime in brain activity (in more than two decades of frequencies) and provided new parameters for noninvasive experimental studies of the brain.

E. Novikov; A. Novikov; D. Shannahoff-Khalsa; B. Schwartz; J. Wright

1997-01-01

117

Decoding patterns of human brain activity.  

PubMed

Considerable information about mental states can be decoded from noninvasive measures of human brain activity. Analyses of brain activity patterns can reveal what a person is seeing, perceiving, attending to, or remembering. Moreover, multidimensional models can be used to investigate how the brain encodes complex visual scenes or abstract semantic information. Such feats of "brain reading" or "mind reading," though impressive, raise important conceptual, methodological, and ethical issues. What does successful decoding reveal about the cognitive functions performed by a brain region? How should brain signals be spatially selected and mathematically combined to ensure that decoding reflects inherent computations of the brain rather than those performed by the decoder? We highlight recent advances and describe how multivoxel pattern analysis can provide a window into mind-brain relationships with unprecedented specificity, when carefully applied. However, as brain-reading technology advances, issues of neuroethics and mental privacy will be important to consider. PMID:21943172

Tong, Frank; Pratte, Michael S

2011-09-19

118

Rat brain docosahexaenoic acid metabolism is not altered by a 6 day intracerebral ventricular infusion of bacterial lipopolysaccharide  

PubMed Central

In a rat model of neuroinflammation, produced by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide (LPS), we reported that the brain concentrations of non-esterified brain arachidonic acid (AA, 20:4 n-6) and its eicosanoid products PGE2 and PGD2 were increased, as were AA turnover rates in certain brain phospholipids and the activity of AA-selective cytosolic phospholipase A2 (cPLA2). The activity of Ca2+-independent iPLA2, which is thought to be selective for the release of docosahexaenoic acid (DHA, 22:6 n-3) from membrane phospholipid, was unchanged. In the present study, we measured parameters of brain DHA metabolism in comparable artificial cerebrospinal fluid (control) and LPS-infused rats. In contrast to the reported changes in markers of AA metabolism, the brain non-esterified DHA concentration and DHA turnover rates in individual phospholipids were not significantly altered by LPS infusion. The formation rates of AA-CoA and DHA-CoA in a microsomal brain fraction were also unaltered by the LPS infusion. These observations indicate that LPS-treatment upregulates markers of brain AA but not DHA metabolism. All of which are consistent with other evidence that suggest different sets of enzymes regulate AA and DHA recycling within brain phospholipids and that only selective increases in brain AA metabolism occur following a 6 day LPS infusion.

Rosenberger, Thad A.; Villacreses, Nelly E.; Weis, Margaret T.; Rapoport, Stanley I.

2010-01-01

119

Aripiprazole brain concentration is altered in P-glycoprotein deficient mice.  

PubMed

P-glycoprotein (P-gp) is a transporter that mediates the tissue disposition of numerous drugs. To evaluate the role of P-glycoprotein (P-gp) in aripiprazole tissue distribution and penetration across the blood-brain barrier, mice deficient in the P-gp gene (Abcb1a/b-/-) were dosed intraperitoneally with 2 microg/g mouse of the antipsychotic drug aripiprazole. Wildtype FVB mice were administered the same dose as transgenic animals. At one, two, and three hours after dosing, blood and tissue samples were collected and assayed for aripiprazole concentration by HPLC. Deficiency of P-gp did not result in significantly altered plasma drug concentrations but had dramatic effects on drug concentrations in brain tissue. At 1, 2, and 3 h after dosing, aripiprazole brain concentrations in the Abcb1a/b-/- mice were 4.6-, 4.1- and 3.0-fold higher, respectively (P<0.01), compared with the wildtype mice. Increases in drug concentration were also observed in testes and muscle in Abcb1a/b -/- mice. All other tissues including gut, lung, heart, kidney, liver, and spleen did not show significant differences between the two groups. These data provide evidence that aripiprazole is a transportable substrate of P-gp. Thus, factors influencing P-gp activity within the blood brain barrier in humans may have implications for the therapeutic effects and tolerability of aripiprazole. PMID:19239981

Wang, Jun-Sheng; Zhu, Hao-Jie; Donovan, Jennifer L; Yuan, Hong-Jie; Markowitz, John S; Geesey, Mark E; Devane, C Lindsay

2009-02-23

120

Altered brain sodium channel transcript levels in human epilepsy  

Microsoft Academic Search

Normal, and perhaps pathological, characteristics of neuronal excitability are related to the distribution and density of voltage-gated ion channels such as the sodium channel. We studied normal and epileptic human brain using the ligase detection reaction to measure the relative quantities of mRNAs encoding sodium channel subtypes 1 and 2. Normal brains exhibited characteristic 1:2 ratios which varied by brain

Anthony J. Lombardo; Ruben Kuzniecky; Richard E. Powers; George B. Brown

1996-01-01

121

Ethanol and acetaldehyde alter NTPDase and 5'-nucleotidase from zebrafish brain membranes.  

PubMed

Alcohol abuse is an acute health problem throughout the world and alcohol consumption is linked to the occurrence of several pathological conditions. Here we tested the acute effects of ethanol on NTPDases (nucleoside triphosphate diphosphohydrolases) and 5'-nucleotidase in zebrafish (Danio rerio) brain membranes. The results have shown a decrease on ATP (36.3 and 18.4%) and ADP (30 and 20%) hydrolysis after 0.5 and 1% (v/v) ethanol exposure during 60 min, respectively. In contrast, no changes on 5'-nucleotidase activity were observed in zebrafish brain membranes. Ethanol in vitro did not alter ATP and ADP hydrolysis, but AMP hydrolysis was inhibited at 0.5, and 1% (23 and 28%, respectively). Acetaldehyde in vitro, in the range 0.5-1%, inhibited ATP (40-85%) and ADP (28-65%) hydrolysis, whereas AMP hydrolysis was reduced (52, 58 and 64%) at 0.25, 0.5 and 1%, respectively. Acetate in vitro did not alter these enzyme activities. Semi-quantitative expression analysis of NTPDase and 5'-nucleotidase were performed. Ethanol treatment reduced NTPDase1 and three isoforms of NTPDase2 mRNA levels. These findings demonstrate that acute ethanol intoxication may influence the enzyme pathway involved in the degradation of ATP to adenosine, which could affect the responses mediated by adenine nucleotides and nucleosides in zebrafish central nervous system. PMID:17698255

Rico, Eduardo Pacheco; Rosemberg, Denis Broock; Senger, Mario Roberto; de Bem Arizi, Marcelo; Dias, Renato Dutra; Souto, André Arigony; Bogo, Maurício Reis; Bonan, Carla Denise

2007-07-04

122

Functional Brain Imaging Alterations in Acne Patients Treated With Isotretinoin  

Microsoft Academic Search

Objective: Although there have been case reports suggesting a relationship be- tween treatment with the acne medica- tion isotretinoin and the development of depression and suicide, this topic remains controversial. In order for isotretinoin to cause depression, it must have an effect on the brain; however, the effects of isotretinoin on brain functioning in acne patients have not been established.

J. Douglas Bremner; Negar Fani; M. S. Ali Ashraf; John R. Votaw; Marijn E. Brummer; D. Thomas Cummins; Viola Vaccarino; Mark M. Goodman; D. Lai Reed; Sajid Siddiq; Charles B. Nemeroff

2005-01-01

123

Correlation between platelet and brain PLA2 activity.  

PubMed

The phospholipase A2 (PLA2) enzymes have been implicated in several neuropsychiatry disorders and activity alterations have been described in brain and platelet. Since brain tissue is not readily available for the measurement of PLA2 activity, it would be of interest to test directly whether PLA2 activities in both tissues are correlated. We performed this task assessing PLA2 activity in platelets and hippocampus collected simultaneously from 19 patients undergoing temporal lobectomy for treatment of refractory epilepsy. Our findings suggest that total PLA2 activity in platelets may reflect the total activity of the enzyme in the brain (rs=0.59, p=0.008). However in our sample no correlations were found between the subgroups of the enzyme in brain and in platelets. This lack of correlations may be due to different effects of drug treatment on the PLA2 subtypes. In face of the difficulty to obtain brain tissues from living patients, further studies with larger drug-free samples are warranted to clarify whether the use of platelets is a reliable strategy to reflect the subtypes of PLA2 activity in the brain. PMID:23880350

Talib, Leda L; Valente, Kette D; Vincentiis, Silvia; Gattaz, Wagner F

2013-07-21

124

In vivo evidence of global and focal brain alterations in anorexia nervosa  

Microsoft Academic Search

Brain alterations are known to be associated with anorexia nervosa (AN) and tend to be distributed across brain structures, with only a few reports describing focal damage. Magnetic resonance images of 21 anorexic patients with different disease duration and 27 control subjects were acquired and compared using voxel-based morphometry (VBM). Patients had a significant reduction of total white matter (WM)

Andrea Boghi; Sara Sterpone; Stefano Sales; Federico D'Agata; Gianni Boris Bradac; Giuseppina Zullo; Donato Munno

2011-01-01

125

Altered pattern of brain dopamine synthesis in male adolescents with attention deficit hyperactivity disorder  

Microsoft Academic Search

BACKGROUND: Limited data from positron emission tomography (PET) studies of subjects with attention-deficit\\/hyperactivity disorder (ADHD) indicate alterations in brain dopamine neurotransmission. However, these studies have used conventional univariate approaches that are less sensitive to detect complex interactions that may exist between different brain dopamine pathways and individual symptoms of ADHD. We aimed to investigate these potential interactions in adolescents with

Hans Forssberg; Elisabeth Fernell; Susanna Waters; Nicholas Waters; Joakim Tedroff

2006-01-01

126

Morphine-conditioned cue alters c-Fos protein expression in the brain of crayfish.  

PubMed

With a highly organized stereotypic behavior and a simplified neuronal system that is characterized by cellular modularity, crayfish (Orconectes rusticus) represents an excellent model that we used in this study to explore how a drug-conditioned-cue alters c-Fos protein expression in the brain of an invertebrate species. The first set of experiments revealed that a single injection of different doses of morphine (3.0 ?g/g, 6.0 ?g/g and 12.0 ?g/g) into the circulatory system of crayfish significantly increased locomotor activity. Repeated injections of morphine increased locomotion at lower doses (3.0 ?g/g and 6.0 ?g/g), and decreased locomotion at a higher dose of 12.0 ?g/g. The second experiment revealed that a repeated or single injection of morphine serves as reward when paired with a distinct visual environment. In the third experiment, we found that the c-Fos profile of morphine treated crayfish in an unconditioned environment did not show a significant increase from the basal level comparable to saline treated crayfish. The brains of crayfish were more active during exposure to the cue-elicited drug conditioned environment than the unconditioned environment. These results indicate that chronic morphine treatment alone is not sufficient to induce changes in the expression of c-Fos; instead, morphine-environment pairing in a specific context contributes to the expression of alterations in c-Fos regulation. The enhancement of c-Fos expression in the brain of crayfish seems to reflect the sensory or anticipatory facets of conditioning that suggests that potential and even unanticipated hypotheses in drug addiction can emerge from studies of addiction in crayfish. PMID:21524693

Dziopa, Leah; Imeh-Nathaniel, Adebobola; Baier, Dana; Kiel, Michael; Sameera, Sayeed; Brager, Adam; Beatriz, Vega; Nathaniel, Thomas I

2011-04-15

127

Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.  

PubMed

Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction. PMID:21652031

Muhammad, Arif; Kolb, Bryan

2011-05-23

128

The slowed brain: cortical oscillatory activity in hepatic encephalopathy.  

PubMed

Oscillatory activity of the human brain has received growing interest as a key mechanism of large-scale integration across different brain regions. Besides a crucial role of oscillatory activity in the emergence of other neurological and psychiatric diseases, recent evidence indicates a key role in the pathophysiology of hepatic encephalopathy (HE). This review summarizes the current knowledge on pathological alterations of oscillatory brain activity in association with liver dysfunction and HE in the context of spontaneous brain activity, motor symptoms, sensory processing, and attention. The existing literature demonstrates a prominent slowing of the frequency of oscillatory activity as shown for spontaneous brain activity at rest, with respect to deficits of motor behavior and motor symptoms, and in the context of visual attention processes. The observed slowing extends across different subsystems of the brain and has been confirmed across different frequency bands, providing evidence for ubiquitous changes of oscillatory activity in HE. For example, the frequency of cortico-muscular coherence in HE patients appears at the frequency of the mini-asterixis (?12Hz), while cirrhotics without overt signs of HE show coherence similar to healthy subjects, i.e. at 13-30Hz. Interestingly, the so-called critical flicker frequency (CFF) as a measure of the processing of an oscillating visual stimulus has emerged as a useful tool to quantify HE disease severity, correlating with behavioral and neurophysiological alterations. Moreover, the CFF reliably distinguishes patients with manifest HE from cirrhotics without any signs of HE and healthy controls using a cut-off frequency of 39Hz. In conclusion, oscillatory activity is globally slowed in HE in close association with HE symptoms and disease severity. Although the underlying causal mechanisms are not yet understood, these results indicate that pathological changes of oscillatory activity play an important role in the pathophysiology of HE. PMID:23603113

Butz, Markus; May, Elisabeth S; Häussinger, Dieter; Schnitzler, Alfons

2013-04-16

129

Self-Stimulation Alters Human Sensory Brain Responses  

Microsoft Academic Search

Human electrocortical potentials evoked by self-administered auditory and visual stimuli manifest much smaller amplitude and faster poststimulus timing than do average brain responses evoked by identical machine-delivered stimuli. Auditory evoked potentials show this \\

Edward W. P. Schafer; Marilyn M. Marcus

1973-01-01

130

Alterations of Brain Biochemistry and Development of Behavior.  

National Technical Information Service (NTIS)

This study seeks to determine the effects of prenatal and early postnatal depletion of brain catecholamines and serotonin on an animal's development, behavior, and psychomotor capabilities. Drugs were used to deplete selectively the amines or serotonin. T...

F. E. Shideman

1965-01-01

131

Perinatal Risk Factors Altering Regional Brain Structure in the Preterm Infant  

ERIC Educational Resources Information Center

|Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between…

Thompson, Deanne K.; Warfield, Simon K.; Carlin, John B.; Pavlovic, Masa; Wang, Hong X.; Bear, Merilyn; Kean, Michael J.; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.

2007-01-01

132

Lead-Induced Alterations of Glial Fibrillary Acidic Protein (GFAP) in the Developing Rat Brain  

Microsoft Academic Search

The developing nervous system is preferentially vulnerable to lead exposure with alterations in neuronal and glial cells of the brain. The present study examined early lead-induced alterations in the developing astrocyte population by examination of the developmentally regulated astrocyte specific protein, glial fibrillary acidic protein (GFAP). A developmental profile (Postnatal Day (PND) 6, 9, 12, 15, 20, and 25) for

G. Jean Harry; Tamara J. Schmitt; Zhaolong Gong; Hayes Brown; Nasser Zawia; Hugh L. Evans

1996-01-01

133

Sustained deep-tissue pain alters functional brain connectivity.  

PubMed

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity. PMID:23718988

Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly

2013-04-11

134

A continuous fluorometric assay for phospholipase A 2 activity in brain cytosol  

Microsoft Academic Search

Alterations in phospholipase A2 (PLA2) activity have been implicated in Alzheimer disease and other neurological disorders, although brain PLA2 activity is currently measured using lengthy, non-continuous assays. We describe herein a rapid, continuous assay in which we measured PLA2 activity in mouse brain cytosol (CB-57). Brains were homogenized in HEPES buffer (pH 7.5) and the cytosolic fraction was prepared by

Danny E. Yarger; Casey B. Patrick; Stanley I. Rapoport; Eric J. Murphy

2000-01-01

135

Arachidonic Acid Metabolism in Brain Physiology and Pathology: Lessons from Genetically Altered Mouse Models  

PubMed Central

The arachidonic acid (AA) cascade involves the release of AA from the membrane phospholipids by a phospholipase A2 (PLA2), followed by its subsequent metabolism to bioactive prostanoids by cyclooxygenases (COX) coupled with terminal synthases. Altered brain AA metabolism has been implicated in neurological, neurodegenerative and psychiatric disorders. The development of genetically altered mice lacking specific enzymes of the AA cascade has helped to elucidate the individual roles of these enzymes in brain physiology and pathology. The roles of AA and its metabolites in brain physiology, with a particular emphasis on the PLA2 /COX pathway, are summarized, and the specific phenotypes of genetically altered mice relevant to brain physiology and neurotoxic models are discussed.

Bosetti, Francesca

2007-01-01

136

Foetal Alcohol Spectrum Disorders and alterations in brain and behaviour.  

PubMed

The term 'Foetal Alcohol Spectrum Disorders (FASD)' refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range of severity of effects and mechanisms involved. In particular, neuroimaging studies have demonstrated overall and regional volumetric and surface area reductions, abnormalities in the shape of particular brain regions, and reduced and increased densities for white and grey matter, respectively. Neurobehaviourally, FASD consists of a continuum of long-lasting deficits affecting multiple aspects of cognition and behaviour. Experimental studies have also provided evidence of the vulnerability of the CNS to the teratogenic effects of ethanol and have provided new insight on the influence of risk factors in the type and severity of observed brain abnormalities. Finally, the potential molecular mechanisms that underlie the neuroteratological effects of alcohol are discussed, with particular emphasis on the role of glial cells in long-term neurodevelopmental liabilities. PMID:19147799

Guerri, Consuelo; Bazinet, Alissa; Riley, Edward P

2009-01-15

137

Can subjective experience cause brain activity?  

Microsoft Academic Search

Comments on a central disagreement in a dialog between D. Bindra and R. W. Sperry (1970) as to whether subjective experience (e.g., pain) can have a causal effect of brain activity. Sperry maintains that subjective experience itself directly determines the further course of brain activity. The author's views are that emergent properties are presumably \\

Zenon W. Pylyshyn

1972-01-01

138

Early brain injury alters the blood-brain barrier phenotype in parallel with ?-amyloid and cognitive changes in adulthood.  

PubMed

Clinical studies suggest that traumatic brain injury (TBI) hastens cognitive decline and development of neuropathology resembling brain aging. Blood-brain barrier (BBB) disruption following TBI may contribute to the aging process by deregulating substance exchange between the brain and blood. We evaluated the effect of juvenile TBI (jTBI) on these processes by examining long-term alterations of BBB proteins, ?-amyloid (A?) neuropathology, and cognitive changes. A controlled cortical impact was delivered to the parietal cortex of male rats at postnatal day 17, with behavioral studies and brain tissue evaluation at 60 days post-injury (dpi). Immunoglobulin G extravasation was unchanged, and jTBI animals had higher levels of tight-junction protein claudin 5 versus shams, suggesting the absence of BBB disruption. However, decreased P-glycoprotein (P-gp) on cortical blood vessels indicates modifications of BBB properties. In parallel, we observed higher levels of endogenous rodent A? in several brain regions of the jTBI group versus shams. In addition at 60?dpi, jTBI animals displayed systematic search strategies rather than relying on spatial memory during the water maze. Together, these alterations to the BBB phenotype after jTBI may contribute to the accumulation of toxic products, which in turn may induce cognitive differences and ultimately accelerate brain aging. PMID:23149553

Pop, Viorela; Sorensen, Dane W; Kamper, Joel E; Ajao, David O; Murphy, M Paul; Head, Elizabeth; Hartman, Richard E; Badaut, Jérôme

2012-11-14

139

Hexachlorophene induced alterations in brain carbohydrate metabolism of wistar rat  

Microsoft Academic Search

Effect of repeated oral administration of hexachlorophene (HCP) on glycolytic and oxidative pathways was studied in the rat brain. The rats were divided into three batches of six in each batch. The first batch was treated with paralytic dose (60 mg. kg . day) of HCP for 7 days. The second batch of animals was treated with sublethal dose (18

W. Rajendra; P. Venkateswara Rao; N. Suhasini; P. Sailaja

1992-01-01

140

Alterations in hippocampal neurogenesis following traumatic brain injury in mice  

Microsoft Academic Search

Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed

Radoslaw Rola; Shinichiro Mizumatsu; Shinji Otsuka; Duncan R. Morhardt; Linda J. Noble-Haeusslein; Kelly Fishman; Matthew B. Potts; John R. Fike

2006-01-01

141

Altered Sleep Brain Functional Connectivity in Acutely Depressed Patients  

Microsoft Academic Search

Recent evidence suggests that problems in information processing within neural networks may underlie depressive disease. In this study, we investigated whether sleep functional brain net- works are abnormally organized during a major depressive episode (MDE). We characterized spatial patterns of functional connectivity by computing the ''synchronization likelihood'' (SL) of 19 sleep EEG channels in 11 acutely depressed patients (42 (20-51)

Samuël J. J. Leistedt; Nathalie Coumans; Martine Dumont; Jean-Pol Lanquart; Cornelis J. Stam; Paul Linkowski

2009-01-01

142

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?  

Microsoft Academic Search

Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive

K. J. S. Anand; Frank M. Scalzo

2000-01-01

143

Fetal and neonatal origins of altered brain development  

Microsoft Academic Search

Abnormal development of the brain during fetal life is now thought to contribute to the aetiology of many neurological disorders that manifest throughout life. Many factors are likely to underlie such abnormal development including genetic makeup and an adverse intrauterine environment. This review will focus on prenatal hypoxic\\/ischaemic injury, inflammatory\\/infective insults and preterm birth. A range of experimental models have

Sandra Rees; Terrie Inder

2005-01-01

144

Alterations in brain monoamine neurotransmitter release at high pressure  

Microsoft Academic Search

High pressure exposure produces neurological changes which manifest as tremors, EEG changes and convulsions. Since previous studies have implicated the involvement of the monoaminergic system in these symptoms, it was of interest to study monoamine release at high pressure. Synaptosomes isolated from guinea pig brain were used to follow monoamine efflux at 68 ATA. The major observation was a decrease

S. C. Gilman; J. S. Colton; A. J. Dutka

1989-01-01

145

Opiate receptor in normal and drug altered brain function  

Microsoft Academic Search

Recent biochemical identification of the receptor site for pharmacological actions of opiates helps elucidate how these drugs relieve pain, elicit euphoria and `addiction', and provides simple, direct approaches to developing potentially non-addicting analgesics. The isolation of a morphine-like peptide which may be a central nervous system neurotransmitter sheds light on normal brain mechanisms regulating pain and emotion.

Solomon H. Snyder

1975-01-01

146

Phytoestrogens decrease brain calcium-binding proteins but do not alter hypothalamic androgen metabolizing enzymes in adult male rats.  

PubMed

Phytoestrogen [plant estrogenic-like molecule(s)] research has grown rapidly in recent years due to their potential health benefits. However, little is known about phytoestrogen's effects on the CNS. Androgen metabolizing enzymes are known to regulate neuroendocrine functions and reproductive behaviors, while calcium-binding proteins are associated with protecting against neurodegenerative diseases. Therefore, we examined aromatase and 5alpha-reductase enzyme activities in the medial basal hypothalamic and preoptic area (mbh-poa) and characterized mbh-poa and amygdala (amy) calbindin and calretinin levels (via Western analysis) from animals fed a phytoestrogen-free (P-free) vs. a phytoestrogen-containing diet [(P-600); that had 600 microg/g of phytoestrogens]. After approximately 5 weeks on the diets, the male rats were killed at 105 days. P-600 plasma phytoestrogen levels were 78-fold higher than the P-free values and the mbh-poa phytoestrogen content was 8-fold higher than the P-free group, demonstrating the passage of phytoestrogens into brain. In general, brain aromatase or 5alpha-reductase activity levels were not significantly altered by the experimental diets. However, independent of brain site (i.e., mbh-poa or amy) the abundance of calbindin from male P-600 rats was significantly lower than P-free animals. Conversely, for calretinin there were no significant alterations in the mbh-poa tissue site, while in the amy a similar pattern of expression was seen to that of the calbindin results. These data suggest that consumption of phytoestrogens via a soy diet for a relatively short interval can significantly: (1) elevate plasma and brain phytoestrogens levels and (2) decrease brain calcium-binding proteins without altering brain androgen metabolizing enzymes. PMID:10720621

Lephart, E D; Thompson, J M; Setchell, K D; Adlercreutz, H; Weber, K S

2000-03-17

147

Protein kinase activators alter glial cholesterol esterification  

SciTech Connect

Similar to nonneural tissues, the activity of glial acyl-CoA cholesterol acyltransferase is controlled by a phosphorylation and dephosphorylation mechanism. Manipulation of cyclic AMP content did not alter the cellular cholesterol esterification, suggesting that cyclic AMP is not a bioregulator in this case. Therefore, the authors tested the effect of phorbol-12-myristate 13-acetate (PMA) on cellular cholesterol esterification to determine the involvement of protein kinase C. PMA has a potent effect on cellular cholesterol esterification. PMA depresses cholesterol esterification initially, but cells recover from inhibition and the result was higher cholesterol esterification, suggesting dual effects of protein kinase C. Studies of other phorbol analogues and other protein kinase C activators such as merezein indicate the involvement of protein kinase C. Oleoyl-acetyl glycerol duplicates the effect of PMA. This observation is consistent with a diacyl-glycerol-protein kinase-dependent reaction. Calcium ionophore A23187 was ineffective in promoting the effect of PMA. They concluded that a calcium-independent and protein C-dependent pathway regulated glial cholesterol esterification.

Jeng, I.; Dills, C.; Klemm, N.; Wu, C.

1986-05-01

148

Spongiform alterations in brain biopsies of presenile dementia  

Microsoft Academic Search

Spongiform lesions were observed in close association with typical presenile alterations in three of six frontal lobe biopsies taken in presenile demented patients without any familial relationship. These findings are discussed in relation with recent investigations indicating the production of spongiform lesions after inoculation of nervous tissue from an Alzheimer patient to animals and the effects of saline extract of

J. Flament-Durand; A. M. Couck

1979-01-01

149

Brain Viscoelasticity Alteration in Chronic-Progressive Multiple Sclerosis  

Microsoft Academic Search

IntroductionViscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE) is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS) is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry

Kaspar-Josche Streitberger; Ingolf Sack; Dagmar Krefting; Caspar Pfüller; Jürgen Braun; Friedemann Paul; Jens Wuerfel

2012-01-01

150

Alteration of Blood–Brain Barrier Integrity by Retroviral Infection  

Microsoft Academic Search

The blood–brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy\\/Tropical Spastic Paraparesis (HAM\\/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have

Philippe V. Afonso; Simona Ozden; Marie-Christine Cumont; Danielle Seilhean; Luis Cartier; Payam Rezaie; Sarah Mason; Sophie Lambert; Michel Huerre; Antoine Gessain; Pierre-Olivier Couraud; Claudine Pique; Pierre-Emmanuel Ceccaldi; Ignacio A. Romero

2008-01-01

151

Pattern of microstructural brain tissue alterations in Fabry disease  

Microsoft Academic Search

Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI\\u000a shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD.\\u000a \\u000a To quantify brain structural changes in clinically affected male and female patients with FD we performed a prospective Diffusion–Tensor\\u000a Imaging (DTI) study in 27 adult

Andreas Fellgiebel; Martin Mazanek; Catharina Whybra; Michael Beck; Ralf Hartung; Kay-Maria Müller; Armin Scheurich; Paulo R. Dellani; Peter Stoeter; Matthias J. Müller

2006-01-01

152

[Brain, psyche and physical activity].  

PubMed

Modern technical and biochemical methods allow investigation of hemodynamic and metabolic responses of the human brain during muscular work. Following a general introduction to the topic results from selected studies on endogenous opioid peptides, pain sensitivity and psyche, regional cerebral blood flow and cerebral glucose metabolism, amino acid transport across the blood-brain barrier, impact of physical work on the serotonergic system, influence of oxygen partial pressure on neurotransmitters and hormones during exercise, role of the brain as performance limiting factor as well as age-related changes in cerebral blood flow and hypothalamo-pituitary-adrenal/-gonadal axis function will be presented. PMID:11149280

Hollmann, W; Strüder, H K

2000-11-01

153

Alterations of Blood-Brain Barrier and Associated Factors in Acute Liver Failure  

PubMed Central

Brain edema in acute liver failure (ALF) remains lethal. Cytotoxic mechanisms associated with brain edema have been well recognized, but the role of vasogenic mechanisms of brain edema has not been explored. Intact tight junctions (TJs) between brain capillary endothelial cells are critical for normal BBB function. Recent reports found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. However, the role of TJ in ALF has not been completely understood. This paper reviews the role of the paracellular tight junction in the increased selective BBB permeability that leads to brain edema in ALF and furthermore explores the effect of systemic inflammatory cytokines on the tight junction dysfunction.

Cui, Wei; Sun, Cui-Ming; Liu, Pei

2013-01-01

154

Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice  

PubMed Central

Background Binge-drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol use disorders. Methods In order to determine if adolescent ethanol binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5g/kg/day i.g., post-natal days P28-37) and assessed during adulthood (P60-P88). An array of neurotransmitter-specific genes, behavioral tests (i.e. reversal learning, prepulse inhibition, and open field), and post-mortem brain structure using MRI and immunohistochemistry, were employed to assess persistent alterations in adult brain. Results At P38, 24 hours after adolescent ethanol (AE) binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38-P88) resulted in decreased neurotransmitter mRNA, e.g. an average decrease of 56%. Following adolescent ethanol treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by adolescent ethanol treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following adolescent ethanol. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons. Conclusions Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking.

Coleman, Leon G.; He, Jun; Lee, Joohwi; Styner, Martin; Crews, Fulton T.

2013-01-01

155

Altered Small-World Brain Networks in Temporal Lobe in Patients with Schizophrenia Performing an Auditory Oddball Task  

PubMed Central

The functional architecture of the human brain has been extensively described in terms of complex networks characterized by efficient small-world features. Recent functional magnetic resonance imaging (fMRI) studies have found altered small-world topological properties of brain functional networks in patients with schizophrenia (SZ) during the resting state. However, little is known about the small-world properties of brain networks in the context of a task. In this study, we investigated the topological properties of human brain functional networks derived from fMRI during an auditory oddball (AOD) task. Data were obtained from 20 healthy controls and 20 SZ; A left and a right task-related network which consisted of the top activated voxels in temporal lobe of each hemisphere were analyzed separately. All voxels were detected by group independent component analysis. Connectivity of the left and right task-related networks were estimated by partial correlation analysis and thresholded to construct a set of undirected graphs. The small-worldness values were decreased in both hemispheres in SZ. In addition, SZ showed longer shortest path length and lower global efficiency only in the left task-related networks. These results suggested small-world attributes are altered during the AOD task-related networks in SZ which provided further evidences for brain dysfunction of connectivity in SZ.

Yu, Qingbao; Sui, Jing; Rachakonda, Srinivas; He, Hao; Pearlson, Godfrey; Calhoun, Vince D.

2011-01-01

156

Activities That Build the Young Child's Brain.  

ERIC Educational Resources Information Center

This book presents 350 classroom-tested activities for use with children to create an environment that will stimulate young children's brains. Designed to be used by families, classroom teachers, family childcare providers, or others caring for young children, the book includes information on current brain research and describes interest areas in…

Gellens, Suzanne R.

157

Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.  

PubMed

The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain. PMID:18038759

Lemberg, A; Fernández, M A; Ouviña, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J

2007-12-01

158

BTECH: A Platform to Integrate Genomic, Transcriptomic and Epigenomic Alterations in Brain Tumors  

Microsoft Academic Search

The identification of molecular signatures predictive of clinical behavior and outcome in brain tumors has been the focus\\u000a of many studies in the recent years. Despite the wealth of data that are available in the public domain on alterations in\\u000a the genome, epigenome and transcriptome of brain tumors, the underlying molecular mechanisms leading to tumor initiation and\\u000a progression remain largely

Min Wang; Hehuang Xie; Wendy Stellpflug; Veena Rajaram; Maria de Fatima Bonaldo; Stewart Goldman; Tadanori Tomita; Marcelo Bento Soares

2011-01-01

159

Phylogenetic origins of early alterations in brain region proportions.  

PubMed

Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups. PMID:20332607

Charvet, Christine J; Sandoval, Alexis L; Striedter, Georg F

2010-03-23

160

Phylogenetic Origins of Early Alterations in Brain Region Proportions  

PubMed Central

Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.

Charvet, Christine J.; Sandoval, Alexis L.; Striedter, Georg F.

2010-01-01

161

Altered small-world brain networks in schizophrenia patients during working memory performance.  

PubMed

Impairment of working memory (WM) performance in schizophrenia patients (SZ) is well-established. Compared to healthy controls (HC), SZ patients show aberrant blood oxygen level dependent (BOLD) activations and disrupted functional connectivity during WM performance. In this study, we examined the small-world network metrics computed from functional magnetic resonance imaging (fMRI) data collected as 35 HC and 35 SZ performed a Sternberg Item Recognition Paradigm (SIRP) at three WM load levels. Functional connectivity networks were built by calculating the partial correlation on preprocessed time courses of BOLD signal between task-related brain regions of interest (ROIs) defined by group independent component analysis (ICA). The networks were then thresholded within the small-world regime, resulting in undirected binarized small-world networks at different working memory loads. Our results showed: 1) at the medium WM load level, the networks in SZ showed a lower clustering coefficient and less local efficiency compared with HC; 2) in SZ, most network measures altered significantly as the WM load level increased from low to medium and from medium to high, while the network metrics were relatively stable in HC at different WM loads; and 3) the altered structure at medium WM load in SZ was related to their performance during the task, with longer reaction time related to lower clustering coefficient and lower local efficiency. These findings suggest brain connectivity in patients with SZ was more diffuse and less strongly linked locally in functional network at intermediate level of WM when compared to HC. SZ show distinctly inefficient and variable network structures in response to WM load increase, comparing to stable highly clustered network topologies in HC. PMID:22701611

He, Hao; Sui, Jing; Yu, Qingbao; Turner, Jessica A; Ho, Beng-Choon; Sponheim, Scott R; Manoach, Dara S; Clark, Vincent P; Calhoun, Vince D

2012-06-06

162

Brain Electrical Activity Mapping (BEAM) Interim Guidelines.  

National Technical Information Service (NTIS)

The BEAM equipment is a neurophysiological diagnostic device which converts the output of a 20-channel electroencephalograph (EEG) into a color contour map of the electrical activity at the surface of the brain. Preliminary data on clinical efficacy indic...

J. Murphy

1983-01-01

163

Similarities in lindane induced alteration in cytochrome P450s and associated signaling events in peripheral blood lymphocytes and brain.  

PubMed

Studies were initiated to investigate the similarities in alterations in cytochrome P450s (CYPs) and associated signaling events in brain and peripheral blood lymphocytes (PBL) induced by lindane, an organochlorine pesticide. Adult male albino wistar rats were treated orally with different doses (2.5- or 5.0- or 10- or 15mg/kg/body weight) of lindane daily for 4days. In another experiment, the treatment of low dose (2.5mg/kg) of lindane was continued for 15- and 21days. A dose- and time-dependent increase was observed in the activity of CYP dependent enzymes in brain microsomes and PBL isolated from the treated rats. However, the magnitude of induction was several folds less in PBL. As observed in brain, RT-PCR and Western immunoblotting demonstrated that increase in CYP enzymes in PBL is due to the increase in the mRNA expression of specific CYP isoenzymes. Similarities were also observed in activation of ERK and JNK MAP kinases and c-jun in PBL or brain isolated from rats treated with lindane. Similarities in the induction of CYPs and activation of MAP kinases in PBL and brain suggest that CYP expression profiles in PBL could be used for monitoring the exposure and toxicity of environmental chemicals. PMID:23927878

Khan, Anwar Jamal; Sharma, Amit; Dinesh, K; Parmar, Devendra

2013-08-06

164

Selectively altering belief formation in the human brain  

PubMed Central

Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people’s tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained “good news/bad news effect.” Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability.

Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W.; Rees, Geraint; Dolan, Raymond J.

2012-01-01

165

Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain  

SciTech Connect

The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD) brains. In frontal cortex and hippocampus of control cases, the most pronounced ODC immunoreactivity was found in the nucleus. In possible and definite AD the immunoreactivity had shifted to the cytoplasm. In cerebellum of control cases, ODC staining was found in a small portion of Purkinje cells, mostly in the nucleus. In AD, both possible and definite, the number of stained Purkinje cells increased significantly and immunoreactivity was shifted to the cytoplasm, even though it was still prominent in the nucleus. In conclusion, our study reveals an early shift of the ODC immunoreactivity in AD from the nuclear compartment towards the cytoplasm.

Nilsson, Tatjana [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden)]. E-mail: Tatjana.Nilsson@ki.se; Bogdanovic, Nenad [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Volkman, Inga [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Winblad, Bengt [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Folkesson, Ronnie [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Benedikz, Eirikur [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden)

2006-06-02

166

Vasopressin alters female sexual behaviour by acting on the brain independently of alterations in blood pressure  

Microsoft Academic Search

Subcutaneous (s.c.) administration of Arg-vasopressin (AVP) prolongs retention of a learned behaviour and elevates arterial blood pressure1,2. Intracerebroventricular (i.c.v.) injection of a thousandfold lower dose of AVP than needed with s.c. injection produces the same behavioural effect, suggesting that AVP acts on the brain to control behaviour3. However, as i.c.v. injection of AVP also elevates arterial blood pressure4, it was

P. Södersten; M. Henning; P. Melin; S. Ludin

1983-01-01

167

Evidence for centrophenoxine as a protective drug in aluminium induced behavioral and biochemical alteration in rat brain.  

PubMed

Potential use of various nootropic drugs have been a burning area of research on account of various physical and chemical insult in brain under different toxicological conditions. One of the nootropic drug centrophenoxine, also known as an anti-aging drug has been exploited in the present experiment under aluminium toxic conditions. Aluminium was administered by oral gavage at a dose level of 100 mg/Kg x b x wt/day for a period of six weeks. To elucidate the region specific response, study was carried out in two different regions of brain namely cerebrum and cerebellum. Following aluminium exposure, a significant decrease in the activities of enzymes namely Hexokinase, Lactate dehydrogenase, Succinate dehydrogenase, Mg(2+) dependent ATPase was observed in both the regions. Moreover, the activity of acetylcholinesterase was also reported to be significantly decreased. Post-treatment with centrophenoxine was able to restore the altered enzyme activities and the effect was observed in both the regions of brain although the activity of lactate dehydrogenase and acetylcholinesterase did not register significant increase in the cerebellum region. Further, centrophenoxine was able to improve the altered short-term memory and cognitive performance resulted from aluminium exposure. From the present study, it can be concluded that centrophenoxine has a potential and can be exploited in other toxicological conditions also. PMID:16969689

Nehru, Bimla; Bhalla, Punita; Garg, Aarti

2006-09-13

168

Structural brain alterations associated with dyslexia predate reading onset  

Microsoft Academic Search

Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals

Nora Maria Raschle; Maria Chang; Nadine Gaab

2011-01-01

169

Brain Activation Modulated by Sentence Comprehension  

Microsoft Academic Search

The comprehension of visually presented sentences produces brain activation that increases with the linguistic complexity of the sentence. The volume of neural tissue activated (number of voxels) during sentence comprehension was measured with echoplanar functional magnetic resonance imaging. The modulation of the volume of activation by sentence complexity was observed in a network of four areas: the classical left-hemisphere language

Marcel Adam Just; Patricia A. Carpenter; Timothy A. Keller; William F. Eddy; Keith R. Thulborn

1996-01-01

170

Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease  

Microsoft Academic Search

Summary To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared

Cheryl L. Grady; Maura L. Furey; Pietro Pietrini; Barry Horwitz; Stanley I. Rapoport

2001-01-01

171

Verbal fluency deficits and altered lateralization of language brain areas in individuals genetically predisposed to schizophrenia  

Microsoft Academic Search

Alterations of verbal fluency may correlate with deficits of gray matter volume and hemispheric lateralization of language brain regions like the pars triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high genetic risk (HR) for schizophrenia may clarify if these deficits represent heritable trait markers or state dependent phenomena. We assessed adolescent and young adult HR subjects (N=60) and healthy

Tejas S Bhojraj; Alan N Francis; Rajaprabhakaran Rajarethinam; Shaun Eack; Shreedhar Kulkarni; Konasale M Prasad; Debra M Montrose; Diana Dworakowski; Vaibhav Diwadkar; Matcheri S Keshavan

2009-01-01

172

Prenatal exposure to morphine alters brain ? opioid receptor characteristics in rats  

Microsoft Academic Search

Prenatal morphine exposure alters neither the binding capacity nor the affinity of ligand binding to ? opioid receptors of adult male brains. However, males have significantly higherBmax in the hypothalamus than ovariectomized females. In females, prenatal exposure to morphine reduces theBmax of ? opioid receptors 25% in the hypothalamus and preoptic area. Estrogen treatment increases theBmax of ? opioid receptors

Agnes Rimano´czy; Ilona Vathy

1995-01-01

173

Subchronic antipsychotic drug treatment does not alter brain phospholipid fatty acid composition in rats  

Microsoft Academic Search

Altered membrane phospholipid fatty acid composition is reported in schizophrenia and appears to be reduced by antipsychotic drug treatment. To determine whether antipsychotic drugs have a direct effect on brain phospholipid fatty acid composition, the effects of sub-chronic treatment with a “typical” and an “atypical” antipsychotic drug were determined in adult male Sprague–Dawley rats. Rats were treated with haloperidol (1

Beth Levant; Jennifer F. Crane; Susan E. Carlson

2006-01-01

174

Histopathological alterations in the brain regions of rats after perinatal combined treatment with cadmium and dexamethasone  

Microsoft Academic Search

Industrial and environmental exposure to cadmium (Cd) is well known to produce multiorgan toxicity in humans. Metallothionein (MT) is a cellular ligand for Cd. MT has been shown to protect against Cd-induced toxicity in many organs, including brain. In this study, we described the histopathological alterations in parietal cortex, striatum, hippocampus and cerebellum of rats following perinatal combined exposure to

M. Méndez-Armenta; R. Barroso-Moguel; J. Villeda-Hernández; C. Nava-Ru??z; C. R??os

2001-01-01

175

Alteration of Cyclic Adenosine Monophosphate Response Element Binding Protein in Rat Brain After Hypoglycemic Coma  

Microsoft Academic Search

In the current study, the temporal and regional changes of the transcription factor cyclic adenosine monophosphate response element binding protein (CREB) were investigated in rat brains subjected to 30 minutes of hypoglycemic coma followed by varied periods of recovery using Western blot and confocal microscopy. The total amount of CREB was not altered in any area examined after coma. The

Yi-Bing Ouyang; Qing-Ping He; Xiao-Hu Zhang; Gui-Xia Wang; Bing-Ren Hu

2000-01-01

176

Low levels of copper disrupt brain amyloid-? homeostasis by altering its production and clearance  

PubMed Central

Whereas amyloid-? (A?) accumulates in the brain of normal animals dosed with low levels of copper (Cu), the mechanism is not completely known. Cu could contribute to A? accumulation by altering its clearance and/or its production. Because Cu homeostasis is altered in transgenic mice overexpressing A? precursor protein (APP), the objective of this study was to elucidate the mechanism of Cu-induced A? accumulation in brains of normal mice and then to explore Cu’s effects in a mouse model of Alzheimer’s disease. In aging mice, accumulation of Cu in brain capillaries was associated with its reduction in low-density lipoprotein receptor-related protein 1 (LRP1), an A? transporter, and higher brain A? levels. These effects were reproduced by chronic dosing with low levels of Cu via drinking water without changes in A? synthesis or degradation. In human brain endothelial cells, Cu, at its normal labile levels, caused LRP1-specific down-regulation by inducing its nitrotyrosination and subsequent proteosomal-dependent degradation due in part to Cu/cellular prion protein/LRP1 interaction. In APPsw/0 mice, Cu not only down-regulated LRP1 in brain capillaries but also increased A? production and neuroinflammation because Cu accumulated in brain capillaries and, unlike in control mice, in the parenchyma. Thus, we have demonstrated that Cu’s effect on brain A? homeostasis depends on whether it is accumulated in the capillaries or in the parenchyma. These findings should provide unique insights into preventative and/or therapeutic approaches to control neurotoxic A? levels in the aging brain.

Singh, Itender; Sagare, Abhay P.; Coma, Mireia; Perlmutter, David; Gelein, Robert; Bell, Robert D.; Deane, Richard J.; Zhong, Elaine; Parisi, Margaret; Ciszewski, Joseph; Kasper, R. Tristan; Deane, Rashid

2013-01-01

177

Cannabis use and brain structural alterations in first episode schizophrenia — A region of interest, voxel based morphometric study  

Microsoft Academic Search

Structural alterations of the brain in schizophrenia have been associated with genetic and environmental factors. Among the environmental factors, cannabis use has been associated with increased risk for patients with schizophrenia, but the effect of cannabis on their brain structure is unclear. We examined gray matter alterations in first episode schizophrenia patients (FES) with cannabis use (FES+C; n=15) compared to

Srihari S. Bangalore; Konasale M. R. Prasad; Debra M. Montrose; Dhruman D. Goradia; Vaibhav A. Diwadkar; Matcheri S. Keshavan

2008-01-01

178

Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis?  

PubMed Central

Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7-tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G?) and the loss modulus (G?), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation.

Riek, Kerstin; Millward, Jason M.; Hamann, Isabell; Mueller, Susanne; Pfueller, Caspar F.; Paul, Friedemann; Braun, Jurgen; Infante-Duarte, Carmen; Sack, Ingolf

2012-01-01

179

Brain Stem Evoked Responses in Altered G Environments.  

National Technical Information Service (NTIS)

Due to the importance of the vestibular system in both ground-based and space-based motion sickness, a method of measuring its activity in intact humans is desirable. Since the gravitoinertial end-organ receptors of the vestibular and auditory systems are...

D. A. Ratino G. F. Wilson L. E. Rodriguez L. L. Floyd R. J. Luciani

1989-01-01

180

Physical activity, brain plasticity, and Alzheimer's disease.  

PubMed

In this review we summarize the epidemiological, cross-sectional, and interventional studies examining the association between physical activity and brain volume, function, and risk for Alzheimer's disease. The epidemiological literature provides compelling evidence that greater amounts of physical activity are associated with a reduced risk of dementia in late life. In addition, randomized interventions using neuroimaging tools have reported that participation in physical activity increases the size of prefrontal and hippocampal brain areas, which may lead to a reduction in memory impairments. Consistent with these findings, longitudinal studies using neuroimaging tools also find that the volume of prefrontal and hippocampal brain areas are larger in individuals who engaged in more physical activity earlier in life. We conclude from this review that there is convincing evidence that physical activity has a consistent and robust association with brain regions implicated in age-related cognitive decline and Alzheimer's disease. In addition to summarizing this literature we provide recommendations for future research on physical activity and brain health. PMID:23085449

Erickson, Kirk I; Weinstein, Andrea M; Lopez, Oscar L

2012-10-16

181

Metabolomics Reveals Metabolic Alterations by Intrauterine Growth Restriction in the Fetal Rabbit Brain  

PubMed Central

Background Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5–10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. Methodology/Principal Findings At gestation day 25, IUGR was induced in two New Zealand rabbits by 40–50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. Conclusions IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress mechanisms. Overall findings identified aspargine, ornithine, N-acetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment.

van Vliet, Erwin; Eixarch, Elisenda; Illa, Miriam; Arbat-Plana, Ariadna; Gonzalez-Tendero, Anna; Hogberg, Helena T.; Zhao, Liang; Hartung, Thomas; Gratacos, Eduard

2013-01-01

182

Nanotools for Neuroscience and Brain Activity Mapping  

PubMed Central

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.

Alivisatos, A. Paul; Andrews, Anne M.; Boyden, Edward S.; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Fraser, Scott E.; Lippincott-Schwartz, Jennifer; Looger, Loren L.; Masmanidis, Sotiris; McEuen, Paul L.; Nurmikko, Arto V.; Park, Hongkun; Peterka, Darcy S.; Reid, Clay; Roukes, Michael L.; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J.; Shepard, Kenneth L.; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S.; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei

2013-01-01

183

Nanotools for neuroscience and brain activity mapping.  

PubMed

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function. PMID:23514423

Alivisatos, A Paul; Andrews, Anne M; Boyden, Edward S; Chun, Miyoung; Church, George M; Deisseroth, Karl; Donoghue, John P; Fraser, Scott E; Lippincott-Schwartz, Jennifer; Looger, Loren L; Masmanidis, Sotiris; McEuen, Paul L; Nurmikko, Arto V; Park, Hongkun; Peterka, Darcy S; Reid, Clay; Roukes, Michael L; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J; Shepard, Kenneth L; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei

2013-03-20

184

Growth-Related Neural Reorganization and the Autism Phenotype: A Test of the Hypothesis that Altered Brain Growth Leads to Altered Connectivity  

ERIC Educational Resources Information Center

|Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and…

Lewis, John D.; Elman, Jeffrey L.

2008-01-01

185

Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity  

Microsoft Academic Search

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico- cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections.

John D. Lewis; Jeffrey L. Elman

2008-01-01

186

Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine.  

PubMed

Trace amines (TAs) such as ?-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons. Taar1 transgenic mice did not show overt behavioral abnormalities under baseline conditions, despite augmented extracellular levels of dopamine and noradrenaline in the accumbens nucleus (Acb) and of serotonin in the medial prefrontal cortex. In vitro, this was correlated with an elevated spontaneous firing rate of monoaminergic neurons in the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus as the result of ectopic TAAR1 expression. Furthermore, Taar1 transgenic mice were hyposensitive to the psychostimulant effects of amphetamine, as it produced only a weak locomotor activation and failed to alter catecholamine release in the Acb. Attenuating TAAR1 activity with the selective partial agonist RO5073012 restored the stimulating effects of amphetamine on locomotion. Overall, these data show that Taar1 brain overexpression causes hyposensitivity to amphetamine and alterations of monoaminergic neurotransmission. These observations confirm the modulatory role of TAAR1 on monoamine activity and suggest that in vivo the receptor is either constitutively active and/or tonically activated by ambient levels of endogenous agonist(s). PMID:22763617

Revel, Florent G; Meyer, Claas A; Bradaia, Amyaouch; Jeanneau, Karine; Calcagno, Eleonora; André, Cédric B; Haenggi, Markus; Miss, Marie-Thérèse; Galley, Guido; Norcross, Roger D; Invernizzi, Roberto W; Wettstein, Joseph G; Moreau, Jean-Luc; Hoener, Marius C

2012-07-04

187

Heritability of working memory brain activation.  

PubMed

Although key to understanding individual variation in task-related brain activation, the genetic contribution to these individual differences remains largely unknown. Here we report voxel-by-voxel genetic model fitting in a large sample of 319 healthy, young adult, human identical and fraternal twins (mean ± SD age, 23.6 ± 1.8 years) who performed an n-back working memory task during functional magnetic resonance imaging (fMRI) at a high magnetic field (4 tesla). Patterns of task-related brain response (BOLD signal difference of 2-back minus 0-back) were significantly heritable, with the highest estimates (40-65%) in the inferior, middle, and superior frontal gyri, left supplementary motor area, precentral and postcentral gyri, middle cingulate cortex, superior medial gyrus, angular gyrus, superior parietal lobule, including precuneus, and superior occipital gyri. Furthermore, high test-retest reliability for a subsample of 40 twins indicates that nongenetic variance in the fMRI brain response is largely due to unique environmental influences rather than measurement error. Individual variations in activation of the working memory network are therefore significantly influenced by genetic factors. By establishing the heritability of cognitive brain function in a large sample that affords good statistical power, and using voxel-by-voxel analyses, this study provides the necessary evidence for task-related brain activation to be considered as an endophenotype for psychiatric or neurological disorders, and represents a substantial new contribution to the field of neuroimaging genetics. These genetic brain maps should facilitate discovery of gene variants influencing cognitive brain function through genome-wide association studies, potentially opening up new avenues in the treatment of brain disorders. PMID:21795540

Blokland, Gabriëlla A M; McMahon, Katie L; Thompson, Paul M; Martin, Nicholas G; de Zubicaray, Greig I; Wright, Margaret J

2011-07-27

188

Breakdown of the Blood-Brain Barrier in Stress Alters Cognitive Dysfunction and Induces Brain Pathology: New Perspectives for Neuroprotective Strategies  

Microsoft Academic Search

\\u000a Emotional, psychological or environmental stress (e.g., heat or nanoparticles) influences brain function. However, the detailed\\u000a mechanisms of stress induced brain dysfunction are not well known. Research carried out in our laboratory since last 20 years\\u000a show that various kinds of stressors depending on their magnitude and durations alter the blood-brain barrier (BBB) permeability\\u000a to proteins leading to brain pathology. These

Hari Shanker Sharma; Aruna Sharma

189

Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors  

PubMed Central

Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, ?14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.

Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M.

2011-01-01

190

Thinking Patterns, Brain Activity and Strategy Choice  

NASA Astrophysics Data System (ADS)

In this study we analyzed the relationship between thinking patterns, behavior and associated brain activity. Subjects completed a self-report assessing whether they could voluntarily stop thinking or not, and were then divided into two groups: those with the ability to stop thinking and those without. We measured subjects' brain activity using magnetoencephalography while giving them a series of tasks intended to encourage or discourage spontaneous thinking. Our findings revealed differences between the two groups in terms of which portions of the brain were active during the two types of task. A second questionnaire confirmed a relationship between the ability to stop thinking and strategy choices in a dilemma game. We found that subjects without the ability to stop thinking had a tendency to choose cooperative behavior.

Nishimura, Kazuo; Okada, Akira; Inagawa, Michiyo; Tobinaga, Yoshikazu

2012-03-01

191

Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions  

SciTech Connect

Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

Weiland, N.G.; Wise, P.M.

1987-11-01

192

Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2  

PubMed Central

Abstract Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism.

Dennis, Emily L.; Jahanshad, Neda; Rudie, Jeffrey D.; Brown, Jesse A.; Johnson, Kori; McMahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant; Martin, Nicholas G.; Wright, Margaret J.; Bookheimer, Susan Y.; Dapretto, Mirella; Toga, Arthur W.

2011-01-01

193

Patients with chronic visceral pain show sex-related alterations in intrinsic oscillations of the resting brain.  

PubMed

Abnormal responses of the brain to delivered and expected aversive gut stimuli have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a visceral pain syndrome occurring more commonly in women. Task-free resting-state functional magnetic resonance imaging (fMRI) can provide information about the dynamics of brain activity that may be involved in altered processing and/or modulation of visceral afferent signals. Fractional amplitude of low-frequency fluctuation is a measure of the power spectrum intensity of spontaneous brain oscillations. This approach was used here to identify differences in the resting-state activity of the human brain in IBS subjects compared with healthy controls (HCs) and to identify the role of sex-related differences. We found that both the female HCs and female IBS subjects had a frequency power distribution skewed toward high frequency to a greater extent in the amygdala and hippocampus compared with male subjects. In addition, female IBS subjects had a frequency power distribution skewed toward high frequency in the insula and toward low frequency in the sensorimotor cortex to a greater extent than male IBS subjects. Correlations were observed between resting-state blood oxygen level-dependent signal dynamics and some clinical symptom measures (e.g., abdominal discomfort). These findings provide the first insight into sex-related differences in IBS subjects compared with HCs using resting-state fMRI. PMID:23864686

Hong, Jui-Yang; Kilpatrick, Lisa A; Labus, Jennifer; Gupta, Arpana; Jiang, Zhiguo; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Ebrat, Bahar; Smith, Suzanne; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

2013-07-17

194

Altered Balance of Proteolytic Isoforms of Pro-Brain-Derived Neurotrophic Factor in Autism  

PubMed Central

Defects in synaptic development and plasticity may lead to autism. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptogenesis and synaptic plasticity. BDNF is synthesized as a precursor, pro-BDNF, which can be processed into either a truncated form or into mature BDNF. Previous studies reported increased BDNF-immunoreactive protein in autism, but the mechanism of this increase has not been investigated. We examined BDNF mRNA by real-time reverse transcription–polymerase chain reaction and BDNF protein by Western blotting and enzyme-linked immunosorbent assay in postmortem fusiform gyrus tissue from 11 patients with autism and 14 controls. BDNF mRNA levels were not different in the autism versus control samples, but total BDNF-like immunoreactive protein, measured by enzyme-linked immunosorbent assay, was greater in autism than in controls. Western blotting revealed greater pro-BDNF and less truncated BDNF in autism compared with controls. These data demonstrate that increased levels of BDNF-immunoreactive protein in autism are not transcriptionally driven. Increased pro-BDNF and reduced truncated BDNF are consistent with defective processing of pro-BDNF to its truncated form. Distortion of the balance among the 3 BDNF isoforms, each of which may exhibit different biological activities, could lead to changes in connectivity and synaptic plasticity and, hence, behavior. Thus, imbalance in proteolytic isoforms is a possible new mechanism for altered synaptic plasticity leading to autism.

Garcia, Kristine L.P.; Yu, Guanhua; Nicolini, Chiara; Michalski, Bernadeta; Garzon, Diego J.; Chiu, Victor S.; Tongiorgi, Enrico; Szatmari, Peter; Fahnestock, Margaret

2012-01-01

195

Ketogenic Diet Prevents Alterations in Brain Metabolism in Young but not Adult Rats after Traumatic Brain Injury  

PubMed Central

Abstract Previous studies have shown that the change of cerebral metabolic rate of glucose (CMRglc) in response to traumatic brain injury (TBI) is different in young (PND35) and adult rats (PND70), and that prolonged ketogenic diet treatment results in histological and behavioral neuroprotection only in younger rat brains. However, the mechanism(s) through which ketones act in the injured brain and the biochemical markers of their action remain unknown. Therefore, the current study was initiated to: 1) determine the effect of injury on the neurochemical profile in PND35 compared to PND70 rats; and 2) test the effect of early post-injury administration of ketogenic diet on brain metabolism in PND35 versus PND70 rats. The data show that alterations in energy metabolites, amino acid, and membrane metabolites were not evident in PND35 rats on standard diet until 24?h after injury, when the concentration of most metabolites was reduced from sham-injured values. In contrast, acute, but transient deficits in energy metabolism were measured at 6?h in PND70 rats, together with deficits in N-acetylaspartate that endured until 24?h. Administration of a ketogenic diet resulted in significant increases in plasma ?-hydroxybutyrate (?OHB) levels. Similarly, brain ?OHB levels were significantly elevated in all injured rats, but were elevated by 43% more in PND35 rats compared to PND70 rats. As a result, ATP, creatine, and phosphocreatine levels at 24?h after injury were significantly improved in the ketogenic PND35 rats, but not in the PND70 group. The improvement in energy metabolism in the PND35 brains was accompanied by the recovery of NAA and reduction of lactate levels, as well as amelioration of the deficits of other amino acids and membrane metabolites. These results indicate that the PND35 brains are more resistant to the injury, indicated by a delayed deficit in energy metabolism. Moreover, the younger brains revert to ketones metabolism more quickly than do the adult brains, resulting in better neurochemical and cerebral metabolic recovery after injury.

Prins, Mayumi L.; Hovda, David A.; Harris, Neil G.

2011-01-01

196

Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain.  

PubMed

P-glycoprotein, an ATP-driven drug efflux pump, is a major obstacle to the delivery of small-molecule drugs across the blood-brain barrier and into the CNS. Here we test a unique signaling-based strategy to overcome this obstacle. We used a confocal microscopy-based assay with isolated rat brain capillaries to map a signaling pathway that within minutes abolishes P-glycoprotein transport activity without altering transporter protein expression or tight junction permeability. This pathway encompasses elements of proinflammatory- (TNF-?) and sphingolipid-based signaling. Critical to this pathway was signaling through sphingosine-1-phosphate receptor 1 (S1PR1). In brain capillaries, S1P acted through S1PR1 to rapidly and reversibly reduce P-glycoprotein transport activity. Sphingosine reduced transport by a sphingosine kinase-dependent mechanism. Importantly, fingolimod (FTY720), a S1P analog recently approved for treatment of multiple sclerosis, also rapidly reduced P-glycoprotein activity; similar effects were found with the active, phosphorylated metabolite (FTY720P). We validated these findings in vivo using in situ brain perfusion in rats. Administration of S1P, FTY720, or FTY729P increased brain uptake of three radiolabeled P-glycoprotein substrates, (3)H-verapamil (threefold increase), (3)H-loperamide (fivefold increase), and (3)H-paclitaxel (fivefold increase); blocking S1PR1 abolished this effect. Tight junctional permeability, measured as brain (14)C-sucrose accumulation, was not altered. Therefore, targeting signaling through S1PR1 at the blood-brain barrier with the sphingolipid-based drugs, FTY720 or FTY720P, can rapidly and reversibly reduce basal P-glycoprotein activity and thus improve delivery of small-molecule therapeutics to the brain. PMID:22949658

Cannon, Ronald E; Peart, John C; Hawkins, Brian T; Campos, Christopher R; Miller, David S

2012-09-04

197

Microwave irradiation decreases ATP, increases free [Mg²?], and alters in vivo intracellular reactions in rat brain.  

PubMed

Rapid inactivation of metabolism is essential for accurately determining the concentrations of metabolic intermediates in the in vivo state. We compared a broad spectrum of energetic intermediate metabolites and neurotransmitters in brains obtained by microwave irradiation to those obtained by freeze blowing, the most rapid method of extracting and freezing rat brain. The concentrations of many intermediates, cytosolic free NAD(P)(+) /NAD(P)H ratios, as well as neurotransmitters were not affected by the microwave procedure. However, the brain concentrations of ATP were about 30% lower, whereas those of ADP, AMP, and GDP were higher in the microwave-irradiated compared with the freeze-blown brains. In addition, the hydrolysis of approximately 1 ?mol/g of ATP, a major in vivo Mg(2+) -binding site, was related to approximately five-fold increase in free [Mg(2+) ] (0.53 ± 0.07 mM in freeze blown vs. 2.91 mM ± 0.48 mM in microwaved brains), as determined from the ratio [citrate]/[isocitrate]. Consequently, many intracellular properties, such as the phosphorylation potential and the ?G' of ATP hydrolysis were significantly altered in microwaved tissue. The determinations of some glycolytic and TCA cycle metabolites, the phosphorylation potential, and the ?G' of ATP hydrolysis do not represent the in vivo state when using microwave-fixed brain tissue. PMID:23013291

Srivastava, Shireesh; Kashiwaya, Yoshihiro; Chen, Xuesong; Geiger, Jonathan D; Pawlosky, Robert; Veech, Richard L

2012-12-01

198

Morphine-conditioned cue alters c-Fos protein expression in the brain of crayfish  

Microsoft Academic Search

With a highly organized stereotypic behavior and a simplified neuronal system that is characterized by cellular modularity, crayfish (Orconectes rusticus) represents an excellent model that we used in this study to explore how a drug-conditioned-cue alters c-Fos protein expression in the brain of an invertebrate species. The first set of experiments revealed that a single injection of different doses of

Leah Dziopa; Adebobola Imeh-Nathaniel; Dana Baier; Michael Kiel; Sayeed Sameera; Adam Brager; Vega Beatriz; Thomas I. Nathaniel

2011-01-01

199

Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status  

Microsoft Academic Search

The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain\\u000a revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty\\u000a demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal\\u000a sensorimotor deficits and with improving orientation. MRI showed almost complete resolution

Aaron J. Clark; Kangmin Lee; William C. Broaddus; Mary Jo Martin; Nitya R. Ghatak; Catherine E. Grossman; Sherman Baker Jr; Ahmet Baykal

2010-01-01

200

Memory disturbances in ”Ecstasy” users are correlated with an altered brain serotonin neurotransmission  

Microsoft Academic Search

Rationale: Methylenedioxymethamphetamine (MDMA) is known to damage brain pre-synaptic serotonin (5-HT) neurons. Since loss of 5-HT neurons\\u000a has been implicated in memory loss, it is important to establish whether MDMA use may produce changes in postsynaptic 5-HT\\u000a receptors and memory function in humans. Objectives: To investigate whether MDMA use leads to compensative alterations in post-synaptic 5-HT2A receptors and whether there

Liesbeth Reneman; Jan Booij; Ben Schmand; Wim van den Brink; Boudewijn Gunning

2000-01-01

201

Alpha-2 adrenergic challenge with guanfacine one month after mild traumatic brain injury: altered working memory and BOLD response.  

PubMed

Alterations in working memory (WM) are common after traumatic brain injury (TBI). Frontal catecholaminergic systems, including the alpha-2 adrenergic system, modulate WM function and may be affected in TBI. We hypothesized that administration of an alpha-2 adrenergic agonist might improve WM after mild TBI (MTBI). Thirteen individuals with MTBI 1month after injury and 14 healthy controls (HC) were challenged with guanfacine and placebo prior to administration of a verbal WM functional MRI task. Guanfacine was associated with improved WM performance in the MTBI but not the HC group. On guanfacine the MTBI group showed increased activation within a WM task-specific region of interest. Findings are consistent with the hypothesis that alterations in WM after MTBI may be improved with the alpha-2 agonist guanfacine. PMID:21767584

McAllister, Thomas W; McDonald, Brenna C; Flashman, Laura A; Ferrell, Richard B; Tosteson, Tor D; Yanofsky, Norman N; Grove, Margaret R; Saykin, Andrew J

2011-07-19

202

Modeling the hemodynamic response to brain activation  

Microsoft Academic Search

Neural activity in the brain is accompanied by changes in cerebral blood flow (CBF) and blood oxygenation that are detectable with functional magnetic resonance imaging (fMRI) techniques. In this paper, recent mathematical models of this hemodynamic response are reviewed and integrated. Models are described for: (1) the blood oxygenation level dependent (BOLD) signal as a function of changes in cerebral

Richard B. Buxton; Kâmil Uluda?; David J. Dubowitz; Thomas T. Liu

2004-01-01

203

Need-information organization of brain activity  

Microsoft Academic Search

The reflex approach to brain activity is in harmony with the anatomical structure of the CNS and its afferent, effector, and central-integrative formations; it is this last component that is most difficult for neurophysiologlcal analysis so far as behavior is concerned. To show conclusively that this statement is correct, it is only necessary to compare advances in the physiology of

P. V. Simonov

1981-01-01

204

Electromagnetic imaging of dynamic brain activity.  

National Technical Information Service (NTIS)

Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach i...

J. Mosher R. Leahy P. Lewis J. Lewine J. George

1991-01-01

205

Active ultramicrobacterial alteration of iron in granite  

NASA Astrophysics Data System (ADS)

Microorganisms are able to exist in extreme environments, where they often form biofilms. We are investigating an iron metabolizing biofilm consortium derived from groundwater draining the Canadian Shield. This was first discovered in the Underground Research Laboratory of Atomic Energy of Canada Ltd., where its influence on the management of nuclear fuel waste was examined. Incubations have shown that the microbial consortium contains different morphological forms. Ultramicrobacteria, 0.3 micrometers diameter cocci, are dominant on magnetite surfaces, which they are able to transform rapidly to hematite. Larger rods, 1.0 micrometers long, aggregate on silicon minerals containing little iron. Carbon is limited in these natural groundwaters so that iron is utilized as an alternative energy source. The cell surface of the organisms and the extracellular polymers of the biofilm are both negatively-charged allowing metal cations to be quickly bound by physicochemical sorption, thus providing nucleation sites for mineralization within the boundaries. The biofilm consortium is able to mediate a wide range of iron reactions. Aerobically a ferric gel is precipitated throughout the biofilm slime, which alters first to ferrihydrite and later to hematite. When anaerobic fermentation produces a reducing environment the iron is converted to the ferrous state which may then be precipitated as ferrous hydroxide, vivianite or siderite. Since iron is widespread in the natural environment, these reactions could have important geochemical implications.

Brown, D. Ann; Sherriff, Barbara L.

1997-07-01

206

Altered Striatal Activation Predicting Real-World Positive Affect in Adolescent Major Depressive Disorder  

PubMed Central

Objective Alterations in reward-related brain function and phenomenological aspects of positive affect are increasingly examined in the development of major depressive disorder. The authors tested differences in reward-related brain function in healthy and depressed adolescents, and the authors examined direct links between reward-related brain function and positive mood that occurred in real-world contexts. Method Fifteen adolescents with major depressive disorder and 28 adolescents with no history of psychiatric disorder, ages 8–17 years, completed a functional magnetic resonance imaging guessing task involving monetary reward. Participants also reported their subjective positive affect in natural environments during a 4-day cell-phone-based ecological momentary assessment. Results Adolescents with major depressive disorder exhibited less striatal response than healthy comparison adolescents during reward anticipation and reward outcome, but more response in dorsolateral and medial prefrontal cortex. Diminished activation in a caudate region associated with this depression group difference was correlated with lower subjective positive affect in natural environments, particularly within the depressed group. Conclusions Results support models of altered reward processing and related positive affect in young people with major depressive disorder and indicate that depressed adolescents’ brain response to monetary reward is related to their affective experience in natural environments. Additionally, these results suggest that reward-processing paradigms capture brain function relevant to real-world positive affect.

Forbes, Erika E.; Hariri, Ahmad R.; Martin, Samantha L.; Silk, Jennifer S.; Moyles, Donna L.; Fisher, Patrick M.; Brown, Sarah M.; Ryan, Neal D.; Birmaher, Boris; Axelson, David A.; Dahl, Ronald E.

2009-01-01

207

Complex networks in brain electrical activity  

NASA Astrophysics Data System (ADS)

This letter reports a method to extract a functional network of the human brain from electroencephalogram measurements. A network analysis was performed on the resultant network and the statistics of the cluster coefficient, node degree, path length, and physical distance of the links, were studied. Even given the low electrode count of the experimental data the method was able to extract networks with network parameters that clearly depend on the type of stimulus presented to the subject. This type of analysis opens a door to studying the cerebral networks underlying brain electrical activity, and links the fields of complex networks and cognitive neuroscience.

Ray, C.; Ruffini, G.; Marco-Pallarés, J.; Fuentemilla, L.; Grau, C.

2007-08-01

208

Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury.  

PubMed

The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions. PMID:21777109

Scheibel, Randall S; Newsome, Mary R; Wilde, Elisabeth A; McClelland, Michelle M; Hanten, Gerri; Krawczyk, Daniel C; Cook, Lori G; Chu, Zili D; Vásquez, Ana C; Yallampalli, Ragini; Lin, Xiaodi; Hunter, Jill V; Levin, Harvey S

2011-07-21

209

The novel antiepileptic drug levetiracetam (ucb L059) induces alterations in GABA metabolism and turnover in discrete areas of rat brain and reduces neuronal activity in substantia nigra pars reticulata  

Microsoft Academic Search

Levetiracetam ((S)-?-ethyl -2-oxo-pyrrolidine acetamide, ucb L059) is a novel anticonvulsant drug presently in clinical development. Its mechanism of action is unknown although a recently reported novel specific binding site for [3H]levetiracetam, unique to brain, may be involved. This binding site has not yet been characterized, but some evidence suggested a possibly indirect interaction with the GABA system. We therefore examined

Wolfgang Löscher; Dagmar Hönack; Petra Bloms-Funke

1996-01-01

210

IRRADIATION ALTERS MMP-2/TIMP-2 SYSTEM AND COLLAGEN TYPE IV DEGRADATION IN BRAIN  

PubMed Central

Purpose Blood-brain barrier (BBB) disruption is one of major consequences of radiation-induced normal tissue injury in the central nervous system. In the present study, we examined the effects of whole brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials Animals received either whole brain irradiation (a single dose of 10 Gy ?-rays or a fractionated dose of 40 Gy ?-rays total) or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The functional activity of MMPs was measured by in situ zymography and degradation of ECM was visualized by collagen type IV immunofluorescence staining. Results A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h post-irradiation and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

2011-01-01

211

Estradiol and ER? agonists enhance recognition memory, and DPN, an ER? agonist, alters brain monoamines  

PubMed Central

Effects of estradiol benzoate (EB), ER?-selective agonist, propyl pyrazole triol (PPT) and ER?-selective agonists, diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks. Treatments were acute (behavior 4 h later) or sub chronic (daily injections for 2 days with behavior 48 h later). Objects were explored in sample trials (T1), and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2–4 h inter-trial delays. Subjects treated sub chronically with EB, DPN, and C-19, but not PPT, discriminated between old and new objects and objects in old and new locations, suggesting that, at these doses and duration of treatments, estrogenic interactions with ER? contributes to enhancements in recognition memory. Acute injections of DPN, but not PPT, immediately after T1, also enhanced discrimination for both tasks (C19 was not investigated). Effects of EB, DPN and PPT on anxiety and locomotion, measured on elevated plus maze and open field, did not appear to account for the mnemonic enhancements. Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing. DPN was associated with alterations in monoamines in several brain areas: indexed by the metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the MHPG/norepinephrine (NE) ratio, NE activity was increased by 60–130% in the prefrontal cortex (PFC) and ventral hippocampus, and NE activity was decreased by 40–80% in the v. diagonal bands and CA1. Levels of the dopamine (DA) metabolite, homovanillic acid (HVA), increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment. The metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was increased in the PFC and CA3, by approximately 20%. No monoaminergic changes were noted in striatum or medial septum. Results suggest that ER? mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur, in part, through alterations in monoaminergic containing systems primarily in PFC and hippocampus.

Jacome, Luis F.; Gautreaux, Claris; Inagaki, Tomoko; Mohan, Govini; Alves, Stephen; Lubbers, Laura S.; Luine, Victoria

2010-01-01

212

Alterations of peptide metabolism and neuropeptidase activity in senile dementia of the Alzheimer's type.  

PubMed

Work in our laboratory has shown that in addition to previously characterized changes in the level of neuropeptides in SDAT brain, the activity of degradative enzymes responsible for peptide metabolism is also affected. In addition to other reported alterations in peptide metabolism, we have observed that SS-28 degradation is increased in Brodmann area 22 whereas substance P degradation is increased in temporal cortex. Changes in the degradation of these neuropeptides known to be affected in SDAT correlate well with alterations in the activity of specific neuropeptidases. Trypsin-like serine protease activity is increased in SDAT Brodmann area 22 which parallels the increased degradation of SS-28. The activity of MEP 24.15 is decreased in temporal cortex which corresponds to the decreased degradation of substance P. Changes in the activity of these degradative enzymes in SDAT brain can potentially affect the action of other neuropeptide substrates because the neuropeptidases discussed here terminate the action of several neuropeptides. As more neuropeptide and degradative peptidase alterations are discovered in SDAT, greater emphasis may be placed on the role that peptides and neuropeptidases play in the progression of SDAT. PMID:9160957

Waters, S M; Davis, T P

1997-04-24

213

Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies.  

PubMed

It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury. PMID:17727901

Schroeter, Matthias L; Ettrich, Barbara; Schwier, Christiane; Scheid, Rainer; Guthke, Thomas; von Cramon, D Yves

2007-07-14

214

Ionizing radiation alters beta-endorphin-like immunoreactivity in brain but not blood  

SciTech Connect

Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also contribute to this behavioral change in the C57BL/6J mouse.

Mickley, G.A.; Stevens, K.E.; Moore, G.H.; Deere, W.; White, G.A.; Gibbs, G.L.; Mueller, G.P.

1983-12-01

215

Assessment of Chemically-Induced Alterations in Brain Development Using Assays of Neuron- and Glia-Localized Proteins.  

National Technical Information Service (NTIS)

Chemical intervention during prenatal or postnatal ontogeny can result in complex biochemical, morphological and behavioral alterations in brain development. As has been shown at the conference, the knowledge of specific actions of a given drug/chemical i...

J. P. O'Callaghan D. B. Miller

1989-01-01

216

Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression  

PubMed Central

Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients’ brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients’ brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients’ brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here.

Mustak, Mohammed S.; Hegde, Muralidhar L.; Dinesh, Athira; Britton, Gabrielle B.; Berrocal, Ruben; Subba Rao, K.; Shamasundar, N. M.; Rao, K. S. J; Sathyanarayana Rao, T. S.

2010-01-01

217

Altered neuroinflammatory, arachidonic acid cascade and synaptic markers in postmortem Alzheimer’s disease brain  

Microsoft Academic Search

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. A recent positron emission tomography imaging study demonstrated upregulated brain arachidonic acid (AA) metabolism in AD patients. Further, a mouse model of AD shows an increase in AA-releasing cytosolic phospholipase A2 (cPLA2) in brain, and a reduction in cPLA2 activity ameliorated cognitive deficits. These

J S Rao; S I Rapoport; H-W Kim

2011-01-01

218

Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain.  

PubMed

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet, a low-Fe diet (ID), or a low-Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (postnatal days [PN] 4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe, increased plasma transferrin (Tf), and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased Tf and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including Mn, chromium, zinc, cobalt, aluminum, molybdenum, and vanadium. Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter-1 and transferrin receptor were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn. PMID:17060373

Garcia, Stephanie J; Gellein, Kristin; Syversen, Tore; Aschner, Michael

2006-10-23

219

Hierarchical Alteration of Brain Structural and Functional Networks in Female Migraine Sufferers  

PubMed Central

Background Little is known about the changes of brain structural and functional connectivity networks underlying the pathophysiology in migraine. We aimed to investigate how the cortical network reorganization is altered by frequent cortical overstimulation associated with migraine. Methodology/Principal Findings Gray matter volumes and resting-state functional magnetic resonance imaging signal correlations were employed to construct structural and functional networks between brain regions in 43 female patients with migraine (PM) and 43 gender-matched healthy controls (HC) by using graph theory-based approaches. Compared with the HC group, the patients showed abnormal global topology in both structural and functional networks, characterized by higher mean clustering coefficients without significant change in the shortest absolute path length, which indicated that the PM lost optimal topological organization in their cortical networks. Brain hubs related to pain-processing revealed abnormal nodal centrality in both structural and functional networks, including the precentral gyrus, orbital part of the inferior frontal gyrus, parahippocampal gyrus, anterior cingulate gyrus, thalamus, temporal pole of the middle temporal gyrus and the inferior parietal gyrus. Negative correlations were found between migraine duration and regions with abnormal centrality. Furthermore, the dysfunctional connections in patients' cortical networks formed into a connected component and three dysregulated modules were identified involving pain-related information processing and motion-processing visual networks. Conclusions Our results may reflect brain alteration dynamics resulting from migraine and suggest that long-term and high-frequency headache attacks may cause both structural and functional connectivity network reorganization. The disrupted information exchange between brain areas in migraine may be reshaped into a hierarchical modular structure progressively.

Li, Guoying; Xiong, Shiwei; Nan, Jiaofen; Li, Jing; Yuan, Kai; von Deneen, Karen M.; Liang, Fanrong; Qin, Wei; Tian, Jie

2012-01-01

220

Cholesterol retention in Alzheimer's brain is responsible for high ?- and ?-secretase activities and A? production  

PubMed Central

Alzheimer’s disease (AD) is characterized by overproduction of A? derived from APP cleavage via ?- and ?-secretase pathway. Recent evidence has linked altered cholesterol metabolism to AD pathogenesis. In this study, we show that AD brain had significant cholesterol retention and high ?- and ?-secretase activities as compared to age-matched non-demented controls (ND). Over one-half of AD patients had an apoE4 allele but none of the ND. ?- and ?-secretase activities were significantly stimulated in vitro by 40 and 80 µm cholesterol in AD and ND brains, respectively. Both secretase activities in AD brain were more sensitive to cholesterol (40 µm) than those of ND (80 µm). Filipin-stained cholesterol overlapped with BACE and A? in AD brain sections. Cholesterol (10–80 µM) added to N2a cultures significantly increased cellular cholesterol, ?- and ?-secretase activities and A? secretion. Similarly, addition of cholesterol (20–80 µM) to cell lysates stimulated both in vitro secretase activities. Ergosterol slightly decreased ?-secretase activity at 20–80 µM, but strongly inhibited ?-secretase activity at 40 µM. Cholesterol depletion reduced cellular cholesterol, ?-secretase activity and A? secretion. Transcription factor profiling shows that several key nuclear receptors involving cholesterol metabolism were significantly altered in AD brain, including decreased LXR-?, PPAR and TR, and increased RXR. Treatment of N2a cells with LXR, RXR or PPAR agonists strongly stimulated cellular cholesterol efflux to HDL and reduced cellular cholesterol and ?-/?-secretase activities. This study provides direct evidence that cholesterol homeostasis is impaired in AD brain and suggests that altered levels or activities of nuclear receptors may contribute to cholesterol retention which likely enhances ?- and ?-secretase activities and A? production in human brain.

Xiong, Huaqi; Callaghan, Debbie; Jones, Aimee; Walker, Douglas G.; Lue, Lih-Fen; Beach, Thomas G.; Sue, Lucia I.; Woulfe, John; Xu, Huaxi; Stanimirovic, Danica B.; Zhang, Wandong

2009-01-01

221

Hageman factor: alterations in physical properties during activation.  

PubMed

Highly purified preparations of Hageman factor, a potent clotpromoting agent in normal mammalian plasma, had a sedimentation coefficient of approximately 5S before activation. After activation, the Hageman factor behaved as a much less soluble or larger molecule during ultracentrifugation and gel filtration. No significant change in sedimentation behavior was noted when the Hageman factor in plasma deficient in plasma thromboplastin antecedent was activated. The altered sedimentation behavior of purified activated Hageman factor probably reflects its decreased solubility in aqueous media. PMID:5844078

Donaldson, V H; Ratnoff, O D

1965-11-01

222

Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats.  

PubMed

Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT (5-hydroxytryptamine, serotonin) levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze (WM) and immobility time by Forced Swim Test (FST). The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT (p<0.05) and 5-HIAA (p<0.05) levels and its withdrawal significantly (p<0.05) decreased brain 5-HT levels. A significant decrease in latency time was exhibited by rats in the WM repeatedly injected with caffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression. PMID:22186305

Khaliq, Saima; Haider, Saida; Naqvi, Faizan; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

2012-01-01

223

Gregarious desert locusts have substantially larger brains with altered proportions compared with the solitarious phase  

PubMed Central

The behavioural demands of group living and foraging have been implicated in both evolutionary and plastic changes in brain size. Desert locusts show extreme phenotypic plasticity, allowing brain morphology to be related to very different lifestyles in one species. At low population densities, locusts occur in a solitarious phase that avoids other locusts and is cryptic in appearance and behaviour. Crowding triggers the transformation into the highly active gregarious phase, which aggregates into dense migratory swarms. We found that the brains of gregarious locusts have very different proportions and are also 30 per cent larger overall than in solitarious locusts. To address whether brain proportions change with size through nonlinear scaling (allometry), we conducted the first comprehensive major axis regression analysis of scaling relations in an insect brain. This revealed that phase differences in brain proportions arise from a combination of allometric effects and deviations from the allometric expectation (grade shifts). In consequence, gregarious locusts had a larger midbrain?optic lobe ratio, a larger central complex and a 50 per cent larger ratio of the olfactory primary calyx to the first olfactory neuropile. Solitarious locusts invest more in low-level sensory processing, having disproportionally larger primary visual and olfactory neuropiles, possibly to gain sensitivity. The larger brains of gregarious locusts prioritize higher integration, which may support the behavioural demands of generalist foraging and living in dense and highly mobile swarms dominated by intense intraspecific competition.

Ott, Swidbert R.; Rogers, Stephen M.

2010-01-01

224

Spontaneous brain activity relates to autonomic arousal  

PubMed Central

Although possible sources and functions of the resting state networks (RSN) of the brain have been proposed, most evidence relies on circular logic and reverse inference. We propose that autonomic arousal provides an objective index of psychophysiological states during rest that may also function as a driving source of the activity and connectivity of RSN. Recording blood oxygenation level-dependent (BOLD) signal using functional magnetic resonance imaging and skin conductance simultaneously during rest in human subjects, we found that the spontaneous fluctuations of BOLD signals in key nodes of RSN are associated with changes in non-specific skin conductance response, a sensitive psychophysiological index of autonomic arousal. Our findings provide evidence of an important role for the autonomic nervous system to the spontaneous activity of the brain during ‘rest’.

Fan, Jin; Xu, Pengfei; Van Dam, Nicholas T.; Eilam-Stock, Tehila; Gu, Xiaosi; Luo, Yuejia; Hof, Patrick R.

2012-01-01

225

Effects of Chronic Marijuana Use on Brain Activity During Monetary Decision-Making  

Microsoft Academic Search

Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous brain regions, including those involved in reward processing and decision-making. However, it remains unclear how long-term, chronic MJ use alters reward-based decision-making. In the present study, using [15O]water PET imaging, we measured brain activity in chronic MJ users, who underwent monitored abstinence from MJ for approximately 24 h

Jatin G Vaidya; Robert I Block; Daniel S O'Leary; Laura B Ponto; Mohamed M Ghoneim; Antoine Bechara

2012-01-01

226

Controlled cortical impact injury and craniotomy result in divergent alterations of pyruvate metabolizing enzymes in rat brain.  

PubMed

Dysregulated glucose metabolism and energy deficit is a characteristic of severe traumatic brain injury (TBI) but its mechanism remains to be fully elucidated. Phosphorylation of pyruvate dehydrogenase (PDH) is the rate-limiting mitochondria enzyme reaction coupling glycolysis to the tricarboxylic acid cycle. Phosphorylation of PDH E1?1 subunit catalyzed by PDH kinase (PDK) inhibits PDH activity, effectively decoupling aerobic glycolysis whereas dephosphorylation of phosphorylated PDHE1?1 by PDH phosphatase (PDP) restores PDH activity. We recently reported altered expression and phosphorylation of pyruvate dehydrogenase (PDH) following TBI. However, little is known about PDK and PDP involvement. We determined PDK (PDK1-4) and PDP isoenzyme (PDP1-2) mRNA and protein expression in rat brain using immunohistochemistry and in situ hybridization techniques. We also quantified PDK and PDP mRNA and protein levels in rat brain following TBI using quantitative real-time PCR and Western blot, respectively. Controlled cortical impact-induced TBI (CCI-TBI) and craniotomy significantly enhanced PDK1-2 isoenzyme mRNA expression level but significantly suppressed PDP1 and PDK4 mRNA expression after the injury (4h to 7days). CCI-TBI and craniotomy also significantly increased PDK1-4 isoenzyme protein expression but suppressed PDP1-2 protein expression in rat brain. In summary, the divergent changes between PDK and PDP expression indicate imbalance between PDK and PDP activities that would favor increased PDHE1?1 phosphorylation and enzyme inhibition contributing to impaired oxidative glucose metabolism in TBI as well as craniotomy. PMID:22193111

Xing, Guoqiang; Ren, Ming; O'Neill, J Timothy; Verma, Ajay; Watson, William D

2011-12-14

227

Cypermethrin alters Glial Fibrillary Acidic Protein levels in the rat brain.  

PubMed

Pyrethroids, widely used insecticides, are biologically active in neurons. Whether they act on the non-neuronal brain cells remains an open question. Thus, the aim of this study was to examine whether Cypermethrin intoxication affects astroglial cells in the rat brain. The levels of Glial Fibrillary Acidic Protein (GFAP) in different brain regions were measured by ELISA following oral treatment with 5 or 10% of LD(50) of Cypermethrin per day for 6 days. A significant decrease of GFAP was observed in different brain regions of treated animals. The cerebral cortex showed the most pronounced effect with GFAP levels reduced to 81% of the controls 2 days after treatment and 77% 21 days after treatment. Although we did not find profound changes in the morphology of astrocytes in Cypermethrin treated animals, the decrease in GFAP suggests that astrocytes were affected by low doses of pyrethroids. The possible consequences were discussed. PMID:21783638

Malkiewicz, Katarzyna; Koteras, Marcin; Folkesson, Ronnie; Brzezinski, Jacek; Winblad, Bengt; Szutowski, Miroslaw; Benedikz, Eirikur

2005-08-02

228

Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior.  

PubMed

Depressive disorders are among the world's greatest public health problems. Na(+), K(+)-ATPase is the established receptor for the steroidal digitalis-like compounds (DLC). Alteration in brain Na(+), K(+)-ATPase and DLC have been detected in depressive disorders raising the hypothesis of their involvement in these pathology. The present study was designed to further elaborate this hypothesis by investigating the behavioral and biochemical consequences of neutralization in brain DLC activity attained by anti-ouabain antibodies administrations, in normal Sprague-Dawley (SD) and in the Flinders Sensitive Line (FSL) of genetically depressed rats. Chronic i.c.v. administration of anti-ouabain antibodies to FSL rats elicited anti-depressive behavior. Administration of anti-ouabain antibodies intracerebroventriculary (i.c.v.) to SD rats significantly changed the levels of catecholamines and their metabolites in the hippocampus, ventral tegmentum and nucleus accumbence. These results are in accordance with the notion that endogenous DLC may be involved in the manifestation of depressive disorders and suggests that alteration in their levels may be of significant therapeutic value. PMID:21700431

Goldstein, Inbal; Lax, Elad; Gispan-Herman, Iris; Ovadia, Haim; Rosen, Haim; Yadid, Gal; Lichtstein, David

2011-06-22

229

Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains Differentially Modulates Src Kinase Activity in Brain Maturation  

PubMed Central

Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1-/- mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/?=?50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (?20–30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1-/- mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain.

Lindquist, Sabine; Karitkina, Diana; Langnaese, Kristina; Posevitz-Fejfar, Anita; Schraven, Burkhart; Xavier, Ramnik; Seed, Brian; Lindquist, Jonathan A.

2011-01-01

230

Altered myoelectric activity in the experimental blind loop syndrome.  

PubMed

Nutrient malabsorption and diarrhea are characteristic of the blind loop syndrome. Alterations in motility have been implicated as a cause of bacterial overgrowth, but the possibility that altered motility may result from alterations in the flora has not been explored. The purpose of this study was to characterize the myoelectric activity of the small intestine in the blind loop rat model. Eight groups of rats were studied: rats with self-filling blind loops, which develop bacterial overgrowth; rats with self-emptying blind loops, which are surgical controls that do not develop overgrowth; unoperated litter mates; rats with self-filling blind loops and unoperated controls treated with chloramphenicol, 200 mg/d i.p.; rats with surgically removed self-filling blind loops; operated control rats; and gnotobiotic rats with self-filling blind loops. In the untreated rats with self-filling blind loops, there was altered myoelectric activity characterized by an increased percentage of slow waves occupied by action potentials and by organized activity similar to the migrating action potential complex. Migrating action potential complex activity and percentage of slow waves occupied by action potentials were significantly decreased with chloramphenicol therapy; that decrease correlated with a decrease in aerobes and anaerobes. Migrating action potential complex activity was abolished in rats with surgically removed self-filling blind loops; they also showed a significant decrease in percentage of slow waves occupied by action potentials. Gnotobiotic rats with self-filling blind loops showed no alteration in myoelectric activity. These data indicate: (a) bacterial overgrowth is associated with a significant increase in percentage of slow waves occupied by action potentials and migrating action potential complex activity; (b) chloramphenicol significantly reduced both percentage of slow waves occupied by action potentials and migrating action potential complex activity; and (c) surgical removal of the loop reduced the alterations in motor function. This study suggests that the altered myoelectric activity in this model of bacterial overgrowth was due, in part, to the abnormal bacterial flora and supports the concept that alterations in motility may contribute to the diarrhea that is characteristic of the blind loop syndrome. PMID:6350361

Justus, P G; Fernandez, A; Martin, J L; King, C E; Toskes, P P; Mathias, J R

1983-09-01

231

Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment  

Microsoft Academic Search

Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in

Yohtaro Numachi; Sumiko Yoshida; Motoyasu Yamashita; Ko Fujiyama; Shigenobu Toda; Hiroo Matsuoka; Yasushi Kajii; Toru Nishikawa

2007-01-01

232

Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation  

PubMed Central

Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered one hour prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol’s effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol’s effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol’s effects on emotional memory formation and hippocampal function are related.

Abercrombie, Heather C.; Jahn, Allison L.; Davidson, Richard J.; Kern, Simone; Kirschbaum, Clemens; Halverson, Jerry

2010-01-01

233

Altered Microstructure Within Social-Cognitive Brain Networks During Childhood in Williams Syndrome.  

PubMed

Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ?26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition. PMID:23709644

Haas, Brian W; Barnea-Goraly, Naama; Sheau, Kristen E; Yamagata, Bun; Ullas, Shruti; Reiss, Allan L

2013-05-24

234

Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA.  

PubMed

Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males. PMID:7792602

Cases, O; Seif, I; Grimsby, J; Gaspar, P; Chen, K; Pournin, S; Müller, U; Aguet, M; Babinet, C; Shih, J C

1995-06-23

235

Gene expression alterations in brains of mice infected with three strains of scrapie  

PubMed Central

Background Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML. Results In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function. Conclusion These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs.

Skinner, Pamela J; Abbassi, Hayet; Chesebro, Bruce; Race, Richard E; Reilly, Cavan; Haase, Ashley T

2006-01-01

236

Cannabis use and brain structural alterations in first episode schizophrenia--a region of interest, voxel based morphometric study.  

PubMed

Structural alterations of the brain in schizophrenia have been associated with genetic and environmental factors. Among the environmental factors, cannabis use has been associated with increased risk for patients with schizophrenia, but the effect of cannabis on their brain structure is unclear. We examined gray matter alterations in first episode schizophrenia patients (FES) with cannabis use (FES+C; n=15) compared to FES without cannabis use (FES-C; n=24) and 42 healthy controls who did not use cannabis. We conducted a voxel based morphometric analysis of a priori determined regions of interest consisting of the CB1 receptor rich brain regions. We observed a decrease in gray matter density in the right posterior cingulate cortex (PCC) in FES+C when compared with FES-C. The results suggest that cannabis use may be associated with altered brain structure, in particular regions rich in CB1 receptors. These findings need to be confirmed by larger, prospective studies. PMID:18248793

Bangalore, Srihari S; Prasad, Konasale M R; Montrose, Debra M; Goradia, Dhruman D; Diwadkar, Vaibhav A; Keshavan, Matcheri S

2008-01-08

237

A Pilot Investigation of Auditory and Visual Entrainment of Brain Wave Activity in Learning Disabled Boys  

Microsoft Academic Search

Research demonstrates that individuals can learn to voluntarily alter and control the frequency of their brain wave activity resulting in a normalization of brainwave patterns and improved functioning. A problem is the length and intensity of training time required to bring about these changes. The purpose of this investigation was to determine if regular and sustained auditory and visual stimulation

John L. Carter; Harold L. Russell

238

Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.  

PubMed

There is increasing evidence that antisocial personality disorder (ASPD) stems from brain abnormalities. However, there are only a few studies investigating brain structure in ASPD. The aim of this study was to find regional coherence abnormalities in resting-state functional MRI of ASPD. Thirty-two ASPD individuals and 34 controls underwent a resting-state functional MRI scan. The regional homogeneity (ReHo) approach was used to examine whether ASPD was related to alterations in resting-state neural activity. Support vector machine discriminant analysis was used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the ASPD individuals and controls. The results showed that, compared with controls, ASPD individuals show lower ReHo in the right cerebellum posterior lobe (Crus1) and the right middle frontal gyrus, as well as higher ReHo in the right middle occipital gyrus (BA 19), left inferior temporal gyrus (BA 37), and right inferior occipital gyrus (cuneus, BA 18). All alternation regions reported a predictive accuracy above 70%. To our knowledge, this study was the first to study the change in regional activity coherence in the resting brain of ASPD individuals. These results not only elucidated the pathological mechanism of ASPD from a resting-state functional viewpoint but also showed that these alterations in ReHo may serve as potential markers for the detection of ASPD. PMID:23804035

Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

2013-08-01

239

Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions.  

PubMed

The metalloproteinase ADAM10 is of importance for Notch-dependent cortical brain development. The protease is tightly linked with ?-secretase activity toward the amyloid precursor protein (APP) substrate. Increasing ADAM10 activity is suggested as a therapy to prevent the production of the neurotoxic amyloid ? (A?) peptide in Alzheimer's disease. To investigate the function of ADAM10 in postnatal brain, we generated Adam10 conditional knock-out (A10cKO) mice using a CaMKII?-Cre deleter strain. The lack of ADAM10 protein expression was evident in the brain cortex leading to a reduced generation of sAPP? and increased levels of sAPP? and endogenous A? peptides. The A10cKO mice are characterized by weight loss and increased mortality after weaning associated with seizures. Behavioral comparison of adult mice revealed that the loss of ADAM10 in the A10cKO mice resulted in decreased neuromotor abilities and reduced learning performance, which were associated with altered in vivo network activities in the hippocampal CA1 region and impaired synaptic function. Histological and ultrastructural analysis of ADAM10-depleted brain revealed astrogliosis, microglia activation, and impaired number and altered morphology of postsynaptic spine structures. A defect in spine morphology was further supported by a reduction of the expression of NMDA receptors subunit 2A and 2B. The reduced shedding of essential postsynaptic cell adhesion proteins such as N-Cadherin, Nectin-1, and APP may explain the postsynaptic defects and the impaired learning, altered network activity, and synaptic plasticity of the A10cKO mice. Our study reveals that ADAM10 is instrumental for synaptic and neuronal network function in the adult murine brain. PMID:23926248

Prox, Johannes; Bernreuther, Christian; Altmeppen, Hermann; Grendel, Jasper; Glatzel, Markus; D'Hooge, Rudi; Stroobants, Stijn; Ahmed, Tariq; Balschun, Detlef; Willem, Michael; Lammich, Sven; Isbrandt, Dirk; Schweizer, Michaela; Horré, Katrien; De Strooper, Bart; Saftig, Paul

2013-08-01

240

Structural Brain Alterations following 5 Days of Intervention: Dynamic Aspects of Neuroplasticity  

Microsoft Academic Search

Activation-dependent brain plasticity in humans on a structural level has been demonstrated in adults after 3 months of training a visio- motor skill. The exact timescale of usage-dependent structural changes, whether days, months, or years, is, however, still de- bated. A better understanding of the temporal parameters may help elucidate to what extent this type of cortical plasticity contributes to

A. May; G. Hajak; S Ganssbauer; T. Steffens; B. Langguth; T Kleinjung; P Eichhammer

2006-01-01

241

Social isolation and social interaction alter regional brain opioid receptor binding in rats  

Microsoft Academic Search

Endogenous opioid systems have been implicated in the consequences of social isolation and in the regulation of social behavior, although their precise role is not clear. There is not much information on a possible locus in the brain at which opioids exert their effects on social behavior. In an effort to address this issue we analyzed regional opioidergic activity upon

Louk J. M. J. Vanderschuren; Elliot A. Stein; Victor M. Wiegant; Jan M. Van Ree

1995-01-01

242

Physical activity alters antioxidant status in exercising elderly subjects  

Microsoft Academic Search

Nutritional adequacy and physical activity are two aspects of a health-promoting lifestyle. Not much is known about antioxidant nutrient requirements for exercising elderly (EE) subjects. The question of whether exercise training alters the status of antioxidant vitamins as well as trace elements in elderly subjects and fails to balance the age-related increase in oxidative stress is addressed in this study.

Anne-Sophie Rousseau; Irène Margaritis; Josiane Arnaud; Henri Faure; Anne-Marie Roussel

2006-01-01

243

In vivo evidence of global and focal brain alterations in anorexia nervosa.  

PubMed

Brain alterations are known to be associated with anorexia nervosa (AN) and tend to be distributed across brain structures, with only a few reports describing focal damage. Magnetic resonance images of 21 anorexic patients with different disease duration and 27 control subjects were acquired and compared using voxel-based morphometry (VBM). Patients had a significant reduction of total white matter (WM) volume and focal gray matter (GM) atrophy in cerebellum, hypothalamus, caudate nucleus and frontal, parietal and temporal areas. The cerebellum was more affected in patients with longer disease duration, whereas the hypothalamic alterations were more pronounced in patients with shorter food restriction. A correlation with body mass index (BMI) and GM was found in the hypothalamus. Our data demonstrate a diffuse reduction of WM together with focal areas of GM atrophy in AN. The finding of a hypothalamic focal atrophy points to hormonal dysfunction and opens the possibility for a central dysregulation of homeostasis. The involvement of temporoparietal areas could account for body image distortion. Finally, the cerebellar GM atrophy confirms previous findings and seems to be a late consequence of AN that could play a role in the chronic phase of the disease. PMID:21546219

Boghi, Andrea; Sterpone, Sara; Sales, Stefano; D'Agata, Federico; Bradac, Gianni Boris; Zullo, Giuseppina; Munno, Donato

2011-05-05

244

Investigating the physiology of brain activation with MRI  

NASA Astrophysics Data System (ADS)

Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

2004-04-01

245

Regulation of brain aromatase activity in rats  

SciTech Connect

The distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of /sup 3/H/sub 2/O formed during the conversion of (1 beta-/sup 3/H)androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. The greatest amount of aromatase activity was found in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA, but not in the amygdala or cerebral cortex. The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities to levels approximating those found in HPOA from intact males. Therefore, the results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats.

Roselli, C.E.; Ellinwood, W.E.; Resko, J.A.

1984-01-01

246

Persistent alterations in regional brain glial fibrillary acidic protein and synaptophysin levels following pre- and postnatal polychlorinated biphenyl exposure.  

PubMed

Pregnant Wistar WU rats were exposed to 0, 5, and 25 mg of the commercial polychlorinated biphenyl (PCB) mixture Aroclor 1254 per kilogram of body weight on Days 10 to 16 of gestation. Pregnant rats were sacrificed on Gestation Day 20 to observe effects on fetal body and brain weights. Male and female offspring were sacrificed on Postnatal Days 21 and 90 (PND21 and PND90, respectively) and examined for treatment-related effects on neurochemical parameters. The concentrations of the neuronal and glial cell markers, synaptophysin and glial fibrillary acidic protein (GFAP), were measured in diverse brain regions from the offspring using immunochemical techniques. The level of calcineurin (a calmodulin-regulated protein phosphatase) activity was measured in cerebellar homogenates. In addition, ethoxyresorufin O-deethylase (EROD) activity was determined in hepatic microsomes as a measure of a well-characterized response to PCB exposure in experimental animals. The major alterations of GFAP levels following maternal PCB treatment were significant increases in the lateral olfactory tract (LOT) and the cerebellum (CB) and significant decreases in the brain stem (BS) of the offspring on PND21 and 90. Synaptophysin levels were significantly decreased relative to controls in the LOT, prefrontal cortex, and striatum of the offspring on PND90. In the BS, synaptophysin levels were significantly decreased relative to controls in male and female weanlings on PND21 and males on PND90; however, significant increases were observed in the BS of females on PND90. No effect of maternal PCB treatment was observed on levels of GFAP and synaptophysin in the dorsal hippocampus on PND21 and 90. Due to analytical restrictions statistical comparisons of GFAP levels were limited to examining the effect of maternal PCB treatment per brain region per sex per time point. Calcineurin activity was decreased in the female CB on PND21, but a significant increase in activity was observed in the female CB on PND90. No effect of maternal PCB treatment was observed on the cerebellar calcineurin activity in male offspring on PND21 and 90. EROD activity was highly induced in maternal microsomes from both PCB treatment groups, but only slightly induced in fetal hepatic microsomes. On PND21 weanling hepatic microsomal EROD activity was highly induced following gestational and lactational PCB exposure; however, on PND90 EROD activity was unaffected by maternal PCB treatment in male offspring and significantly decreased in female offspring. The results of the present study indicate that gestational and lactational exposure to the commercial PCB mixture results in long-term alterations in a neuronal and glial cell markers in specific brain regions of rats. These marker proteins may be useful for determining the structure-activity relationships in PCB-induced developmental neurotoxicity. PMID:8806841

Morse, D C; Plug, A; Wesseling, W; van den Berg, K J; Brouwer, A

1996-08-01

247

Repeated anabolic\\/androgenic steroid exposure during adolescence alters phosphate-activated glutaminase and glutamate receptor 1 (GluR1) subunit immunoreactivity in Hamster brain: correlation with offensive aggression  

Microsoft Academic Search

Male Syrian hamsters (Mesocricetus auratus) treated with moderately high doses (5.0mg\\/kg\\/day) of anabolic\\/androgenic steroids (AAS) during adolescence (P27–P56) display highly escalated offensive aggression. The current study examined whether adolescent AAS-exposure influenced the immunohistochemical localization of phosphate-activated glutaminase (PAG), the rate-limiting enzyme in the synthesis of glutamate, a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models

Shannon G. Fischer; Lesley A. Ricci; Richard H. Melloni

2007-01-01

248

Motor stereotypies and volumetric brain alterations in children with Autistic Disorder.  

PubMed

Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the underlying neurobiology of this neurodevelopmental disorder. In this study, we videoscored stereotypies recorded during semi-structured play sessions from school age children with AD. We examined the effect of severity and persistence over time of stereotypies on brain volumetric changes. Our findings confirmed that the brain volume of school age children with AD is, on average, larger than that of age-matched typically developing children. However, we have failed to detect any sign of volumetric differences in brain regions thought to be particularly linked to the pathophysiology of stereotypies. This negative finding may suggest that, at least with respect to motor stereotypies, functional rather than structural alterations might be the underpinning of these disruptive motor manifestations of autism. PMID:23637709

Goldman, Sylvie; O'Brien, Liam M; Filipek, Pauline A; Rapin, Isabelle; Herbert, Martha R

2013-01-01

249

The influence of preterm birth on structural alterations of the vision-deprived brain.  

PubMed

Differences in brain structures between blind and sighted individuals have not been widely investigated. Furthermore, existing studies have included individuals who were blinded by retinopathy of prematurity, a condition that is associated with premature birth. Recent pediatric research has reported structural differences in individuals who were born prematurely, suggesting that some of the structural abnormalities previously observed in blind individuals may be related to prematurity rather than being specific to blindness. In the present study, we used voxel-based morphometry to investigate gray and white matter differences between 24 blind and 16 sighted individuals. Of the blind individuals, six were born prematurely and 18 at term. Compared to those born at term, blind individuals born preterm showed differences in gray, but not white, matter volumes in various brain regions. When the preterm individuals were excluded from analysis, there were significant differences between blind and sighted individuals. Full-term blind individuals showed regional gray matter decreases in the cuneus, lingual gyrus, middle occipital gyrus, precuneus, inferior and superior parietal lobules, and the thalamus, and gray matter increases in the globus pallidus. They also showed regional white matter decreases in the cuneus, lingual gyrus, and the posterior cingulate. These differences were observed in blind individuals irrespective of blindness onset age, providing evidence for structural alterations in the mature brain. Our findings highlight the importance of considering the potential impact of premature birth on neurodevelopmental outcomes in studies of blind individuals. PMID:22591801

Wan, Catherine Y; Wood, Amanda G; Chen, Jian; Wilson, Sarah J; Reutens, David C

2012-04-11

250

Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions.  

PubMed

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n?=?30) and reactive (n?=?65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD. PMID:24098688

Subirà, Marta; Alonso, Pino; Segalàs, Cinto; Real, Eva; López-Solà, Clara; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Harrison, Ben J; Menchón, José M; Cardoner, Narcís; Soriano-Mas, Carles

2013-09-30

251

Motor stereotypies and volumetric brain alterations in children with Autistic Disorder  

PubMed Central

Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the underlying neurobiology of this neurodevelopmental disorder. In this study, we videoscored stereotypies recorded during semi-structured play sessions from school age children with AD. We examined the effect of severity and persistence over time of stereotypies on brain volumetric changes. Our findings confirmed that the brain volume of school age children with AD is, on average, larger than that of age-matched typically developing children. However, we have failed to detect any sign of volumetric differences in brain regions thought to be particularly linked to the pathophysiology of stereotypies. This negative finding may suggest that, at least with respect to motor stereotypies, functional rather than structural alterations might be the underpinning of these disruptive motor manifestations of autism.

Goldman, Sylvie; O'Brien, Liam M.; Filipek, Pauline A.; Rapin, Isabelle; Herbert, Martha R.

2013-01-01

252

Exercise challenge in Gulf War Illness reveals two subgroups with altered brain structure and function.  

PubMed

Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990-1991) have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n?=?10). This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n?=?18) that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness. PMID:23798990

Rayhan, Rakib U; Stevens, Benson W; Raksit, Megna P; Ripple, Joshua A; Timbol, Christian R; Adewuyi, Oluwatoyin; VanMeter, John W; Baraniuk, James N

2013-06-14

253

Brain Structural Alterations in Obsessive-Compulsive Disorder Patients with Autogenous and Reactive Obsessions  

PubMed Central

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n?=?30) and reactive (n?=?65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.

Subira, Marta; Alonso, Pino; Segalas, Cinto; Real, Eva; Lopez-Sola, Clara; Pujol, Jesus; Martinez-Zalacain, Ignacio; Harrison, Ben J.; Menchon, Jose M.; Cardoner, Narcis; Soriano-Mas, Carles

2013-01-01

254

Spread of epileptic activity in human brain  

NASA Astrophysics Data System (ADS)

For many patients with medically refractory epilepsy surgical resection of the site of seizure onset (epileptic focus) offers the best hope for cure. Determination of the nature of seizure propagation should lead to improved methods for locating the epileptic focus (and hence reduce patient morbidity) and possibly to new treatment modalities directed at blocking seizure spread. Theoretical studies of neural networks emphasize the role of traveling waves for the propagation of activity. However, the nature of seizure propagation in human brain remains poorly characterized. The spread of epileptic activity in patients undergoing presurgical evaluation for epilepsy surgery was measured by placing subdural grids of electrodes (interelectrode spacings of 3-10 mm) over the frontal and temporal lobes. The exact location of each electrode relative to the surface of the brain was determined using 3--D MRI imaging techniques. Thus it is possible to monitor the spread of epileptic activity in both space and time. The observations are discussed in light of models for seizure propagation.

Milton, John

1997-03-01

255

Telomerase Activity and Genetic Alterations in Primary Breast Carcinomas  

PubMed Central

Abstract It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that the ectopic expression of telomerase promotes tumorigenesis via a telomere length-independent mechanism. In this study, the relation between telomerase expression and the extent of chromosomal aberrations was investigated in 62 primary breast carcinomas. Telomerase activity was measured using a polymerase chain reaction-based telomeric repeat amplification protocol assay and 92% of the tumors were found to express telomerase with a relative activity ranging from 0 to 3839.6. Genetic alterations were determined by G-banding and comparative genomic hybridization analysis and 97% of the tumors exhibited chromosomal aberrations ranging from 0 to 44 (average: 10.98). In the overall series, the relationship between telomerase activity levels and genetic changes could be best described by a quadratic model, whereas in tumors with below-average genetic alteration numbers, a significant positive association was recorded between the two variables (coefficient=0.374, P= .017). The relationship between telomerase activity levels and the extent of genetic alteration may reflect the complex effect of telomerase activation upon tumor progression in breast carcinomas.

Papadopoulou, Anna; Trangas, Theoni; Teixeira, Manuel R; Heim, Sverre; Dimitriadis, Euthimios; Tsarouha, Haroula; Andersen, Johan A; Evangelou, Evangelos; Ioannidis, Panayiotis; Agnantis, Niki J; Pandis, Nikos

2003-01-01

256

Response-restriction analysis: II. Alteration of activity preferences.  

PubMed

We used response-restriction (RR) assessments to identify the preferences of 7 individuals with mental retardation for a variety of vocational and leisure activities. We subsequently increased their engagement in nonpreferred activities using several procedures: response restriction per se versus a Premack-type contingency (Study 1), supplemental reinforcement for engagement in target activities (Study 2), and noncontingent pairing of reinforcers with nonpreferred activities (Study 3). Results indicated that preferences are not immutable and can be altered through a variety of relatively benign interventions and that the results of RR assessments may be helpful in determining which types of procedures may be most effective on an individual basis. PMID:12723867

Hanley, Gregory P; Iwata, Brian A; Roscoe, Eileen M; Thompson, Rachel H; Lindberg, Jana S

2003-01-01

257

Specific and Evolving Resting-State Network Alterations in Post-Concussion Syndrome Following Mild Traumatic Brain Injury  

PubMed Central

Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the DSM-IV criteria) at 6 months post-injury compared with 38 mild traumatic brain injury patients with no post-concussion syndrome and 34 healthy controls. All patients underwent magnetic resonance imaging examinations at the subacute (1–3 weeks) and late (6 months) phases after injury. Group-wise differences in functional brain networks were analyzed using graph theory measures. Patterns of long-range functional networks alterations were found in all mild traumatic brain injury patients. Mild traumatic brain injury patients with post-concussion syndrome had greater alterations than patients without post-concussion syndrome. In patients with post-concussion syndrome, changes specifically affected temporal and thalamic regions predominantly at the subacute stage and frontal regions at the late phase. Our results suggest that the post-concussion syndrome is associated with specific abnormalities in functional brain network that may contribute to explain deficits typically observed in PCS patients.

Messe, Arnaud; Caplain, Sophie; Pelegrini-Issac, Melanie; Blancho, Sophie; Levy, Richard; Aghakhani, Nozar; Montreuil, Michele; Benali, Habib; Lehericy, Stephane

2013-01-01

258

CHRONIC FETAL HYPOXIA PRODUCES SELECTIVE BRAIN INJURY ASSOCIATED WITH ALTERED NITRIC OXIDE SYNTHASES  

PubMed Central

OBJECTIVE The impact of chronic hypoxia on the nitric oxide synthase isoenzymes (NOSs) in specific brain structures is unknown. STUDY DESIGN Time-mated pregnant guinea pigs were exposed to 10.5% O2 for 14d (HPX) or room air (NMX); L-NIL (an iNOS inhibitor, 1mg/kg/day) was administered to HPX animals for 14d (L-NIL+HPX). Fetal brains were harvested at term. Multi-labeled immunofluorescence was used to generate a brain injury map. Laser capture microdissection and quantitative PCR were applied and cell injury markers, apoptosis activation, neuron loss, total NO, and the levels of individual NOSs quantified. RESULTS Chronic hypoxia causes selective fetal brain injury rather than globally. Injury is associated with differentially affected NO synthases in both neurons and glial cells, with iNOS up regulated at all injury sites. L-NIL attenuated the injury despite continued hypoxia. CONCLUSIONS These studies demonstrate chronic hypoxia selectively injures the fetal brain in part by the differential regulation of NOSs in an anatomic and cell specific manner.

DONG, Yafeng; YU, Zhiyong; SUN, Yan; ZHOU, Hui; STITES, Josh; NEWELL, Katherine; WEINER, Carl P.

2011-01-01

259

D-Lactate altered mitochondrial energy production in rat brain and heart but not liver  

PubMed Central

Background Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart. Methods Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination. Results In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates. Conclusions DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels.

2012-01-01

260

Motivation alters response bias and neural activation patterns in a perceptual decision-making task.  

PubMed

Motivation has been demonstrated to affect individuals' response strategies in economic decision-making, however, little is known about how motivation influences perceptual decision-making behavior or its related neural activity. Given the important role motivation plays in shaping our behavior, a better understanding of this relationship is needed. A block-design, continuous performance, perceptual decision-making task where participants were asked to detect a picture of an animal among distractors was used during functional magnetic resonance imaging (fMRI). The effect of positive and negative motivation on sustained activity within regions of the brain thought to underlie decision-making was examined by altering the monetary contingency associated with the task. In addition, signal detection theory was used to investigate the effect of motivation on detection sensitivity, response bias and response time. While both positive and negative motivation resulted in increased sustained activation in the ventral striatum, fusiform gyrus, left dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex, only negative motivation resulted in the adoption of a more liberal, closer to optimal response bias. This shift toward a liberal response bias correlated with increased activation in the left DLPFC, but did not result in improved task performance. The present findings suggest that motivation alters aspects of the way perceptual decisions are made. Further, this altered response behavior is reflected in a change in left DLPFC activation, a region involved in the computation of perceptual decisions. PMID:23428623

Reckless, G E; Bolstad, I; Nakstad, P H; Andreassen, O A; Jensen, J

2013-02-18

261

Semantic information alters neural activation during transverse patterning performance  

PubMed Central

Memory tasks can be performed using multiple cognitive strategies, which are mediated by different brain systems. The transverse patterning (TP) task is dependent upon the integrity of the hippocampal system, however, we previously demonstrated successful TP following hippocampal damage using meaningful stimuli and relations (Moses, S.N., Ostreicher, M.L., Rosenbaum, R.S., Ryan, J.D., 2008. Successful transverse patterning in amnesia using semantic knowledge. Hippocampus 18, 121–124). Here, we used magnetoencephalgraphy (MEG) to directly observe the neural underpinnings of TP, and the changes that occur as stimuli and relations become more meaningful. In order to optimize our ability to detect signal from deep, non-dominant, brain sources we implemented the event-related synthetic aperture magnetometry minimum-variance beamformer algorithm (ER-SAM; Cheyne, D., Bakhtazad, L., Gaetz, W., 2006. Spatiotemporal mapping of cortical activity accompanying voluntary movements using an event-related beamforming approach. Human Brain Mapping 27, 213–229) coupled with the partial least squares (PLS) multivariate statistical approach (McIntosh, A.R., Bookstein, F.L., Haxby, J.V., Grady, C.L., 1996. Spatial pattern analysis of function brain images using partial least squares. NeuroImage 3, 143–157; McIntosh, A.R., Lobaugh, N.J., 2004. Partial least squares analysis of neuroimaging data: Applications and advances. NeuroImage 23, S250–S263). We found that increased meaningfulness elicited reduced bilateral hippocampal activation, along with increased activation of left prefrontal and temporal cortical structures, including inferior frontal (IFG), as well as anterior temporal and perirhinal cortices. These activation patterns may represent a shift towards reliance upon existing semantic knowledge. This shift likely permits successful TP performance with meaningful stimuli and relations following hippocampal damage.

Moses, Sandra N.; Ryan, Jennifer D.; Bardouille, Tim; Kovacevic, Natasa; Hanlon, Faith M.; McIntosh, Anthony Randal

2009-01-01

262

Anger Style, Psychopathology, and Regional Brain Activity  

PubMed Central

Depression and anxiety often involve high levels of trait anger and disturbances in anger expression. Reported anger experience and outward anger expression have recently been associated with left-biased asymmetry of frontal cortical activity, assumed to reflect approach motivation. However, different styles of anger expression could presumably involve different brain mechanisms and/or interact with psychopathology to produce various patterns of brain asymmetry. The present study explored these issues by comparing resting regional electroencephalographic activity in participants high in trait anger who differed in anger expression style (high anger-in, high anger-out, both) and participants low in trait anger, with depression and anxiety systematically assessed. Trait anger, not anger-in or anger-out, predicted left-biased asymmetry at medial frontal EEG sites. The anger-in group reported higher levels of anxious apprehension than did the anger-out group. Furthermore, anxious apprehension moderated the relationship between trait anger, anger-in, and asymmetry in favor of the left hemisphere. Results suggest that motivational direction is not always the driving force behind the relationship of anger and left frontal asymmetry. Findings also support a distinction between anxious apprehension and anxious arousal.

Stewart, Jennifer L.; Levin, Rebecca L.; Sass, Sarah M.; Heller, Wendy; Miller, Gregory A.

2010-01-01

263

Temporal Alterations in Cellular Bax:Bcl-2 Ratio following Traumatic Brain Injury in the Rat  

PubMed Central

Cell death/survival following CNS injury may be a result of alterations in the intracellular ratio of death and survival factors. Using immunohistochemistry, Western analysis and in situ hybridization, the expression of the anti-cell death protein, Bcl-2, and the pro-cell death protein, Bax, was evaluated following lateral fluid-percussion (FP) brain injury of moderate severity (2.3–2.6 atm) in adult male Sprague-Dawley rats. By 2 h post-injury, a marked reduction of cellular Bcl-2-immunoreactivity (IR) and a mild decrease in cellular Bax IR were observed in the temporal and occipital cortices, and in the hippocampal CA3 ipsilateral to the site of impact. These decreases in Bcl-2 and Bax IR appeared to precede the overt cell loss in these regions that was evident at 24 h. Immunoblot analysis supported the immunohistochemical data, with a modest but significant reduction in the intensities of both the Bcl-2 and Bax protein bands at 2 h (p < 0.05 compared to sham levels). However, the Bax:Bcl-2 ratio increased significantly at 2 h (2.28 ± 0.13) and remained elevated up to 7 days (2.05 ± 0.13) post-injury compared to sham-injured control tissue (1.62 ± 0.10, p < 0.05). Furthermore, cortical, but not hippocampal, levels of Bax protein increased by 25% (p < 0.05 compared to sham-injured controls) at 24 h post-injury, and returned to control levels by 7 days. In situ hybridization analysis of Bax mRNA revealed increased cellular grain density in the injured cortex (p < 0.05 compared to sham-injured brains), but not in the CA3 region of the injured hippocampus. No injury-induced changes in the expression of Bcl-2 mRNA were observed in any brain region. Taken together, these data suggest that the association between regional post-traumatic cell death and alterations in the cellular ratio of Bcl-2 and Bax may be, in part, due to alterations in mRNA and/or protein expression of the Bcl-2 family of proteins.

STRAUSS, KENNETH I.; ZHANG, CHEN; KRAJEWSKI, STANISLAW; REED, JOHN C.; McINTOSH, TRACY K.

2006-01-01

264

[The noncoherent components of evoked brain activity].  

PubMed

Poststimulus spectral EEG changes and their correlation with evoked potential (EP) were analyzed. The non-stationary components of the brain evoked activity were revealed in 32 volunteers during simple motor reaction and choice reaction to visual stimuli. This nonstationary activity was manifested in poststimulus changes in the mean wave half-period duration (MWHPD) and mean wave half-period power of the delta- and beta-frequency oscillations computed in the EEG realizations after the EP subtraction. The latencies of high-frequency EP components fell into the intervals of the MWHPD decrease and increase in the power of beta-oscillations, and the latencies of low-frequency EP components coincided with the intervals of the MWHPD increase and decrease in the power of delta and beta-oscillations, which pointed to correlation of these changes with the EP. PMID:9929901

Kovalev, V P; Novototski?-Vlasov, V Iu

265

Ischemic preconditioning alters the epigenetic profile of the brain from ischemic intolerance to ischemic tolerance.  

PubMed

Ischemic preconditioning is an innate neuroprotective mechanism in which a sub-injurious ischemic exposure increases the brain's ability to withstand a subsequent, normally injurious ischemic insult. Part of ischemic preconditioning neuroprotection stems from an epigenetic reprogramming of the brain to a phenotype of ischemic tolerance, which results in a gene expression profile different from that observed in the non-injured and ischemia-injured brains. Such neuroprotective reprograming, activated by ischemic preconditioning, requires specific changes in DNA accessibility coordinated with activation of transcriptional activator and repressor proteins, which allows for expression of specific neuroprotective proteins despite a general repression of gene expression. In this review we examine the effects of injurious ischemia and ischemic preconditioning on the regulation of DNA methylation, histone post-translational modifications, and non-coding RNA expression. There is increasing interest in the role of epigenetics in disease pathobiology, and whether and how pharmacological manipulation of epigenetic processes may allow for ischemic neuroprotection. Therefore, a better understanding of the epigenomic determinants underlying the modulation of gene expression that lead to ischemic tolerance or cell death offers the promise of novel neuroprotective therapies that target global reprograming of genomic activity versus individual cellular signaling pathways. PMID:23868468

Thompson, John W; Dave, Kunjan R; Young, Juan I; Perez-Pinzon, Miguel A

2013-10-01

266

Methamphetamine alters blood brain barrier protein expression in mice, facilitating central nervous system infection by neurotropic Cryptococcus neoformans.  

PubMed

Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection. PMID:23532099

Eugenin, Eliseo A; Greco, Jade M; Frases, Susana; Nosanchuk, Joshua D; Martinez, Luis R

2013-03-26

267

Effects of a Carbohydrate Supplement upon Resting Brain Activity  

Microsoft Academic Search

Glucose is a major energy source for the brain, and along with several monosaccharide derivatives as components of brain gangliosides, they play important roles in neurologic function. However, there is little information available on the role of glucose and other monosaccharides on resting brain activity. This study was designed to evaluate the effects of a single dose of a carbohydrate

CHENGHUA WANG; JOANNE S. SZABO; ROSCOE A. DYKMAN

2004-01-01

268

Brain activity and human unilateral chewing: an FMRI study.  

PubMed

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

Quintero, A; Ichesco, E; Myers, C; Schutt, R; Gerstner, G E

2012-10-26

269

Brain activation during anticipation of interoceptive threat.  

PubMed

The current study investigated the neural networks activated during the anticipation of potentially threatening body symptoms evoked by a guided hyperventilation task in a group of participants reporting either high or low fear of unexplained somatic sensations. 15 subjects reporting high and 14 subjects reporting low fear of somatic symptoms first learned that one of two cues predicted the occurrence of a hyperventilation task reliably producing body symptoms in all participants that were rated as more intense and unpleasant in the high fear group. During anticipation of unpleasant symptoms, high fear participants reported more intense body symptoms and showed potentiation of the startle reflex. After this learning session, participants were taken into the fMRI where the same cues either predicted the occurrence of hyperventilation or normoventilation, although the task was never performed in the scanner. During anticipation of hyperventilation all participants showed an increased activation of anterior insula/orbitofrontal cortex and rostral parts of the dorsal anterior cingulate cortex/dorsomedial prefrontal cortex (dACC/dmPFC). Brain activation of high compared to low fear participants differed in two ways. First, high fear participants showed an overall stronger activation of this network during threat and safe conditions indexing stronger anxious apprehension during the entire context. Second, while low fear participants no longer responded with stronger activation to the threat cue after experiencing that the hyperventilation challenge did not follow this cue, high fear participants continued to show stronger activation of the network to this cue. Activation of the rostral dACC/dmPFC was significantly correlated with reported fear of somatic symptoms. These data demonstrate that anticipation of interoceptive threat activates the same network that has been found to be active during anticipation of exteroceptive threat cues. Thus, the current paradigm might provide an innovative method to study anxious apprehension and treatment effects in patients with panic disorder. PMID:22440646

Holtz, Katharina; Pané-Farré, Christiane A; Wendt, Julia; Lotze, Martin; Hamm, Alfons O

2012-03-14

270

Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats  

Microsoft Academic Search

The present study determined the effect of maternal nicotine exposure during the early developmental period on AT1R and AT2R mRNA and protein abundance in the rat brain. Pregnant rats of day-4 gestation were implanted with osmotic minipumps that delivered nicotine at a dose rate of 6 mg\\/kg\\/day for 28 days. Neither fetal nor offspring brain weight was significantly altered by the nicotine

Caiping Mao; Hong Zhang; Daliao Xiao; Liyan Zhu; Yang Ding; Yuying Zhang; Lei Wu; Zhice Xu; Lubo Zhang

2008-01-01

271

Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus  

Microsoft Academic Search

The regimen of estrogen replacement can alter the consequences of estrogen therapy and stressors. To determine the long-term\\u000a effects and interaction of these systems on the brain and periphery, adult female rats were infused with lipopolysaccharide\\u000a (LPS) into the fourth ventricle of the brain for 4 weeks, and ovariectomized rats were administered either constant or pulsed\\u000a regimens of estrogen replacement

L. K. Marriott; K. R. McGann-Gramling; B. Hauss-Wegrzyniak; L. C. Sheldahl; R. A. Shapiro; D. M. Dorsa; G. L. Wenk

2007-01-01

272

Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats  

SciTech Connect

Binding sites for atrial natriuretic factor (ANF-28) were analyzed in discrete brain areas of Brattleboro rats with hereditary diabetes insipidus and Long-Evans (LE) controls by quantitative autoradiography. The maximum binding capacity (Bmax) and affinity constant (Ka) for /sup 125/I-ANF-28 were elevated significantly in the subfornical organ of Brattleboro rats compared to matched LE controls. In contrast, values for Bmax and Ka for /sup 125/I-ANF-28 binding in choroid plexus and area postrema were similar for rats of the two strains. These findings are consistent with a selective upregulation of ANF-28 binding sites in the subfornical organ of Brattleboro rats which exhibit a profound disturbance in body fluid homeostasis. These alterations in ANF-28 binding sites in the subfornical organ may represent a compensatory response to the absence of vasopressin in the Brattleboro rat.

McCarty, R.; Plunkett, L.M.

1986-12-01

273

Alterations of Cortical Electrical Activity in Patients with Sacral Neuromodulator  

Microsoft Academic Search

Objectives: Sacral neuromodulation represents chronic stimulation of the sacral (S3) nerve. So far, the mode of action and neuro-anatomical basis is unclear. Sacral reflex mechanisms as well as pontine or cortical centers of modulation have been postulated. Our aim was to evaluate possible alterations in electroencephalogram (EEG) activity as an indicator of a supraspinally mediated mechanism of sacral neuromodulation.Materials and

P. M. Braun; H. Baezner; C. Seif; G. Boehler; S. Bross; C. C. Eschenfelder; P. Alken; M. Hennerici; P. Juenemann

2002-01-01

274

5-hydroxytryptophan, but not l-tryptophan, alters sleep and brain temperature in rats  

Microsoft Academic Search

The precise role of serotonin (5-hydroxytryptamine) in the regulation of sleep is not fully understood. To further clarify this role for 5-hydroxytryptamine, the 5-hydroxytryptamine precursors l-tryptophan (40 and 80mg\\/kg) and l-5-hydroxytryptophan (25-, 50-, 75-, 100mg\\/kg) were injected intraperitoneally into freely behaving rats 15min prior to dark onset, and subsequent effects on sleep–wake activity and cortical brain temperature were determined. l-5-hydroxytryptophan,

L Imeri; M Mancia; S Bianchi; M. R Opp

1999-01-01

275

Altered functional connectivity in the motor network after traumatic brain injury(CME)  

PubMed Central

Background: A large proportion of survivors of traumatic brain injury (TBI) have persistent cognitive impairments, the profile of which does not always correspond to the size and location of injuries. One possible explanation could be that TBI-induced damage extends beyond obvious lesion sites to affect remote brain networks. We explored this hypothesis in the context of a simple and well-characterized network, the motor network. The aim of this cross-sectional study was to establish the residual integrity of the motor network as an important proof of principle of abnormal connectivity in TBI. Methods: fMRI data were obtained from 12 right-handed patients and 9 healthy controls while they performed the finger-thumb opposition task with the right hand. We used both conventional and psychophysiologic interaction (PPI) analyses to examine the integrity of functional connections from brain regions we found to be activated in the paradigm we used. Results: As expected, the analysis showed significant activations of the left primary motor cortex (M1), right cerebellum (Ce), and bilateral supplementary motor area (SMA) in controls. However, only the activation of M1 survived robust statistical thresholding in patients. In controls, the PPI analysis revealed that left M1, SMA, and right Ce positively interacted with the left frontal cortex and negatively interacted with the right supramarginal gyrus. In patients, we observed no negative interaction and reduced interhemispheric interactions from these seed regions. Conclusions: These observations suggest that patients display compromised activation and connectivity patterns during the finger-thumb opposition task, which may imply functional reorganization of motor networks following TBI. GLOSSARY Ce = cerebellum; GCS = Glasgow Coma Scale; IFG = inferior frontal gyrus; M1 = primary motor cortex; MMSE = Mini-Mental State Examination; MOb = medial frontal gyrus, orbital part; NART = National Adult Reading Test; PPI = psychophysiologic interaction; SMA = supplementary motor area; SMFG = superior medial frontal gyrus; SMG = supramarginal gyrus; SOb = superior frontal gyrus orbital part; TBI = traumatic brain injury.

Kasahara, M.; Menon, D.K.; Salmond, C.H.; Outtrim, J.G.; Taylor Tavares, J.V.; Carpenter, T.A.; Pickard, J.D.; Sahakian, B.J.; Stamatakis, E.A.

2010-01-01

276

Altered brain response without behavioral attention deficits in healthy siblings of schizophrenic patients  

Microsoft Academic Search

Attention deficits are common in schizophrenics and sometimes reported in their healthy relatives. The aim of this study was to analyse the behavioural performance and the brain activation of healthy siblings of schizophrenic patients during a sustained-attention task.Eleven healthy siblings of schizophrenic patients and eleven matched controls performed a Continuous Performance Test (CPT), during 1.5 T fMRI. The stimuli were presented

Gianna Sepede; Antonio Ferretti; Mauro Gianni Perrucci; Francesco Gambi; Fiore Di Donato; Francesco Nuccetelli; Cosimo Del Gratta; Armando Tartaro; Rosa Maria Salerno; Filippo Maria Ferro; Gian Luca Romani

2010-01-01

277

Alterations in free radical scavenger system profile of type I diabetic rat brain  

Microsoft Academic Search

The activities of the enzymes related to glutathione synthesis, degradation, and functions as well as reactive oxygen scavenging\\u000a enzymes were analyzed in different brain regions, such as cerebral hemisphere, cerebellum, brainstem, thalamus, and hypothalamus\\u000a after 1 and 3 mo of streptozotocin-induced diabetes in rats. Parallel studies were also made in age-matched control rats and\\u000a insulin-treated diabetic rats. The content of

Sanjeev Kumar Bhardwaj; Poonam Sharma; Gurcharan Kaur

1998-01-01

278

Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions  

Microsoft Academic Search

Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and\\/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion

N. G. Weiland; P. M. Wise

1987-01-01

279

Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain  

Microsoft Academic Search

Eight-hydroxy-2?-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer's disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activities in nuclear and mitochondrial fractions from frontal (FL), temporal (TL), and parietal (PL) lobes from 8 MCI and 7 LAD patients, and 6

Changxing Shao; Shuling Xiong; Guo-Min Li; Liya Gu; Guogen Mao; William R. Markesbery; Mark A. Lovell

2008-01-01

280

Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis  

SciTech Connect

The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal {sup 125}I irradiation of normal brain, and to determine the effects of an intravenous infusion of {alpha}-defluoromethylornithine (DFMO) on those responses. Adult beagle dogs were irradiated using high activity {sup 125}I sources. Cellular responses were quantified using a histomorphometric analysis. After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. {alpha}-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm{sup 2} were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury. 57 refs., 6 figs.

Fike, J.R.; Gobbel, G.T.; Chou, D. [Univ. of California, San Francisco, CA (United States)] [and others

1995-07-15

281

Alterations in brain structure and functional connectivity in prescription opioid-dependent patients  

PubMed Central

A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n?=??10); from a larger study on prescription opioid dependent patients (n?=??133)] and matched healthy individuals (n?=??10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.

Upadhyay, Jaymin; Maleki, Nasim; Potter, Jennifer; Elman, Igor; Rudrauf, David; Knudsen, Jaime; Wallin, Diana; Pendse, Gautam; McDonald, Leah; Griffin, Margaret; Anderson, Julie; Nutile, Lauren; Renshaw, Perry; Weiss, Roger; Becerra, Lino

2010-01-01

282

Altered small-world brain functional networks and duration of heroin use in male abstinent heroin-dependent individuals  

Microsoft Academic Search

Although previous studies reported addiction-related alteration in resting-state brain connectivity, it is unclear whether these resting-state connectivity alterations were associated with chronic heroin use. In the current study, graph theory analysis (GTA) was applied to detect abnormal topological properties in heroin-dependent individuals. Several statistical parameters, such as degree (D), clustering coefficient (C) and shortest absolute path length (L), were included

Kai Yuan; Wei Qin; Jixin Liu; Qian Guo; Minghao Dong; Jinbo Sun; Yi Zhang; Peng Liu; Wei Wang; Yarong Wang; Qiang Li; Weichuan Yang; Karen M. von Deneen; Mark S. Gold; Yijun Liu; Jie Tian

2010-01-01

283

Altered phospholipid molecular species and glycolipid composition in brain, liver and fibroblasts of Zellweger syndrome.  

PubMed

We studied the altered molecular species of lipids in brain and liver tissues, and fibroblasts from patients with Zellweger syndrome (ZS). ZS cerebellum samples contained a higher amount of sphingomyelin with shorter chain fatty acids compared to that in normal controls. The amount of phosphatidylethanolamine (PE) was less than half of that in controls, with the absence of the PE-type of plasmalogen. Gangliosides were accumulated in the brains and fibroblasts of ZS patients. To investigate whether or not impaired beta-oxidation of very long chain fatty acids and/or plasmalogen synthesis affects glycolipids metabolism, RNAi of peroxisomal acylCo-A oxidase (ACOX1) and glyceronephosphate O-acyltransferase (GNPAT) was performed using cultured neural cells. In neuronal F3-Ngn1 cells, ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucose ceramide glucosyltransferase (UGCG). These results suggest that both impaired beta-oxidation of very long chain fatty acids and plasmalogen synthesis affect glycolipid metabolism in neuronal cells. PMID:23933200

Miyazaki, Celine; Saitoh, Makiko; Itoh, Masayuki; Yamashita, Sumimasa; Miyagishi, Makoto; Takashima, Sachio; Moser, Ann B; Iwamori, Masao; Mizuguchi, Masashi

2013-08-07

284

Alterations of mean diffusivity in brain white matter and deep gray matter in Parkinson's disease.  

PubMed

Although Parkinson's disease is a neurodegenerative disease primarily involving basal ganglia and midbrain, the deficit of white matter is also involved during the disease progression. As the diffusion tensor imaging method is sensitive to the microstructural changes, we investigated the microstructural alterations in white matter and deep gray matter in patients with Parkinson's disease. Brain images of 64 patients and sex- and age-matched 64 healthy controls were obtained from a 3T MRI scanner. Tract-based spatial statistics were used to compare the mean diffusivity of the white matter tract between the groups. Voxel-based analysis was used to compare the mean diffusivity of the subcortical gray matter between the groups. There were white matter deficits in the corticofugal tract, cingulum, uncinate fasciculus, crus of fornix or stria terminalis, corpus callosum, external capsule, superior longitudinal fasciculus, posterior thalamic radiation including optic radiation, and the tracts adjacent to the precuneus and supramarginal gyrus, as indicated by higher mean diffusivity in Parkinson's disease patients than in controls. There were also deficits in the left putamen, pallidum, thalamus, and caudate as indicated by higher mean diffusivity in Parkinson's disease patients than in controls. Using diffusion tensor imaging and multi-methods of image analysis, we successfully characterized and visualized brain white matter and deep gray matter areas with microstructural deficits in Parkinson's disease patients. PMID:23831353

Kim, Hengjun J; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Kim, Namkug; Han, Seungbong; Jang, Eun Hye; Chung, Sun J; Lee, Chong Sik

2013-07-03

285

Mammalian brain and erythrocyte carboxyl methyltransferases are similar enzymes that recognize both D-aspartyl and L-isoaspartyl residues in structurally altered protein substrates.  

PubMed Central

Two purified isozymes of protein carboxyl methyltransferase from bovine brain catalyze the substoichiometric transfer of methyl groups in vitro from S-adenosyl-L-[methyl-3H]methionine to several erythrocyte membrane proteins, which include bands 2.1, 3, and 4.1, as well as several integral membrane polypeptides. D-Aspartic acid beta-[3H]methyl ester has been isolated from proteolytic digests of these methylated proteins, suggesting that protein D-aspartyl residues can serve as methyl-acceptor sites for the two brain enzymes. This formation of D-aspartic acid beta-[3H]methyl ester is competitively inhibited by the peptide L-Val-L-Tyr-L-Pro-L-isoAsp-Gly-L-Ala, which contains an L-aspartyl residue in an unusual beta-peptide linkage. Since this peptide is a stoichiometric substrate for the brain methyltransferases, it appears that one enzymatic activity can catalyze methyl ester formation at both D-aspartyl and L-isoaspartyl sites. In these respects, the activity of both brain isozymes closely resembles those previously described for the erythrocyte enzyme. The results are discussed in terms of a model in which derivatized aspartyl residues in proteins, arising by either racemization or isomerization, are recognized by the methyltransferase; the enzyme may function in either the metabolism or correction of the altered structures. The presence of a similar enzyme in both translationally active (brain) and inactive (erythrocyte) tissues suggests that the reactions are of general importance to cellular integrity. Images

O'Connor, C M; Aswad, D W; Clarke, S

1984-01-01

286

12 CFR 225.25 - Hearings, alteration of activities, and other matters.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Hearings, alteration of activities, and other matters. 225.25 Section...REGULATION Y) Regulations Nonbanking Activities and Acquisitions by Bank Holding Companies...225.25 Hearings, alteration of activities, and other matters. (a)...

2013-01-01

287

Alteration of brain glycogen turnover in the conscious rat after 5 h of prolonged wakefulness  

PubMed Central

Although Glycogen (Glyc) is the main carbohydrate storage component, the role of Glyc in the brain during prolonged wakefulness is not clear. The aim of this study was to determine brain Glyc concentration ([ ]) and turnover time (?) in euglycemic conscious and undisturbed rats, compared to rats maintained awake for 5 h. To measure the metabolism of [1-13C]-labeled Glc into Glyc, 23 rats received a [1-13C]-labeled Glc solution as drink (10% weight per volume in tap water) ad libitum as their sole source of exogenous carbon for a “labeling period” of either 5 (n=13), 24 (n=5) or 48 h (n=5). Six of the rats labeled for 5 h were continuously maintained awake by acoustic, tactile and olfactory stimuli during the labeling period, which resulted in slightly elevated corticosterone levels. Brain [Glyc] measured biochemically after focused microwave fixation in the rats maintained awake (3.9±0.2 ?mol/g, n=6) was not significantly different from that of the control group (4.0±0.1 ?mol/g, n=7; t-test, P>0.5). To account for potential variations in plasma Glc isotopic enrichment (IE), Glyc IE was normalized by N-acetyl-aspartate (NAA) IE. A simple mathematical model was developed to derive brain Glyc turnover time as 5.3 h with a fit error of 3.2 h and NAA turnover time as 15.6 h with a fit error of 6.5 h, in the control rats. A faster ?Glyc (2.9 h with a fit error of 1.2 h) was estimated in the rats maintained awake for 5 h. In conclusion, 5 h of prolonged wakefulness mainly activates glycogen metabolism, but has minimal effect on brain [Glyc].

Morgenthaler, Florence D.; Lanz, Bernard; Petit, Jean-Marie; Frenkel, Hanne; Magistretti, Pierre J.; Gruetter, Rolf

2009-01-01

288

Investigations on alterations of hippocampal circuit function following mild traumatic brain injury.  

PubMed

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological impairments. Two pervasive and disabling symptoms experienced by TBI survivors, memory deficits and a reduction in seizure threshold, are thought to be mediated by TBI-induced hippocampal dysfunction. In order to demonstrate how altered hippocampal circuit function adversely affects behavior after TBI in mice, we employ lateral fluid percussion injury, a commonly used animal model of TBI that recreates many features of human TBI including neuronal cell loss, gliosis, and ionic perturbation. Here we demonstrate a combinatorial method for investigating TBI-induced hippocampal dysfunction. Our approach incorporates multiple ex vivo physiological techniques together with animal behavior and biochemical analysis, in order to analyze post-TBI changes in the hippocampus. We begin with the experimental injury paradigm along with behavioral analysis to assess cognitive disability following TBI. Next, we feature three distinct ex vivo recording techniques: extracellular field potential recording, visualized whole-cell patch-clamping, and voltage sensitive dye recording. Finally, we demonstrate a method for regionally dissecting subregions of the hippocampus that can be useful for detailed analysis of neurochemical and metabolic alterations post-TBI. These methods have been used to examine the alterations in hippocampal circuitry following TBI and to probe the opposing changes in network circuit function that occur in the dentate gyrus and CA1 subregions of the hippocampus (see Figure 1). The ability to analyze the post-TBI changes in each subregion is essential to understanding the underlying mechanisms contributing to TBI-induced behavioral and cognitive deficits. The multi-faceted system outlined here allows investigators to push past characterization of phenomenology induced by a disease state (in this case TBI) and determine the mechanisms responsible for the observed pathology associated with TBI. PMID:23183856

Smith, Colin J; Johnson, Brian N; Elkind, Jaclynn A; See, Jill M; Xiong, Guoxiang; Cohen, Akiva S

2012-11-19

289

Abnormal brain activation during movement observation in patients with conversion paralysis.  

PubMed

Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis. PMID:16213162

Burgmer, Markus; Konrad, Carsten; Jansen, Andreas; Kugel, Harald; Sommer, Jens; Heindel, Walter; Ringelstein, Erich B; Heuft, Gereon; Knecht, Stefan

2005-10-05

290

Dietary myristic acid alters acylated proteins in activated murine macrophages.  

PubMed

After stimulation with select activating agents such as lipopolysaccharide (LPS) or recombinant interferon-gamma (rIFNgamma), several macrophage proteins may be induced, acylated with myristic acid, or both. Our goal in this study was to determine whether altering the levels of myristic acid in the diet would modulate the levels of a specific acylated macrophage protein, MacMARCKS (myristoylated, alanine-rich C kinase substrate), because that fatty acid can be found in substantial quantities in some foods. Thioglycollate-elicited peritoneal macrophages from groups of mice fed diets with various levels of myristic acid (from 0.2 to 99 g/100 g fatty acids) were treated with LPS, phorbol myristate acetate (PMA), or rIFNgamma plus LPS, which are well-established macrophage activating agents. Levels of MacMARCKS were measured by enzyme-linked immunosorbent assay using a rabbit anti-mouse polyclonal antibody against the first 10 amino acids of murine MacMARCKS. A 42-kDa protein with the same molecular weight as MacMARCKS was identified in macrophage lysates by Western analysis using the antibody. Lipopolysaccharide- and PMA-activated macrophages from mice fed the trimyristin diet had significantly greater levels of MacMARCKS than LPS- and PMA-activated macrophages of mice fed the safflower oil-containing diet. The levels of MacMARCKS were also greater in lysates of LPS plus rIFNgamma-stimulated macrophages from mice fed the trimyristin diet and mice fed a diet containing a moderate level of myristic acid (12 g/100 g fatty acids) compared with the lysates of macrophages from mice fed the safflower oil diet. These results indicate that altering the level of myristic acid in the diet may alter the production of specific proteins that may be involved in macrophage activation. PMID:8648429

Hubbard, N E; Socolich, R J; Erickson, K L

1996-06-01

291

Altered neurotransmission in brains of autoimmune mice: pharmacological and neurochemical evidence  

Microsoft Academic Search

Depressive-like behavior is the most profound manifestation of autoimmunity-associated behavioral syndrome in lupus-prone MRL-lpr mice. This led to the hypothesis that chronic autoimmunity and inflammation alter the activity of central serotonergic and dopaminergic systems. Three drugs with a selective mode of action were used to probe the functional status of these two systems in vivo. The behavioral effects of single

Boris Sakic; Susan Lacosta; Judah A Denburg; Henry Szechtman

2002-01-01

292

Correlation between cognitive brain function and electrical brain activity in dementia of Alzheimer type  

Microsoft Academic Search

Summary Psychometric tests which assess cognitive brain function in dementia disorders are partly prone to artifacts, e.g., the experience of the investigator and the cooperation of the patient influences the results. An objective way to assess the degree of cognitive disturbance could be to measure neuronal activity represented by the electrical brain activity. The aim of the present study was

T. Dierks; L. Frölich; R. Ihl; K. Maurer

1995-01-01

293

Brain studies may alter long-held concepts about likely causes of some voice disorders  

SciTech Connect

Two voice disorders long considered to be psychological problems, stuttering and spasmodic dysphonia, have been shown in many persons to have a neurophysiological basis. Investigators at the 155th national meeting of the American Association for the Advancement of Science, in San Francisco, described their findings, which are based on new analytic techniques. The research is being done at the Dallas Center for Vocal Motor Control, Callier Center for Communication Disorders, University of Texas at Dallas Health Science Center. The technology employed to learn what's wrong with the brains, rather than the psyches, of persons with certain speech disorders includes magnetic resonance imaging (MRI), brain electrical activity mapping (BEAM), and single photon emission computerized tomography (SPECT). The results of applying these techniques are combined with quantitative behavioral measures of vocal and nonvocal motor control, language performance, and cognition to arrive at a better understanding of the problem.

Not Available

1989-02-17

294

The Effects of Aerobic Activity on Brain Structure  

PubMed Central

Aerobic activity is a powerful stimulus for improving mental health and for generating structural changes in the brain. We review the literature documenting these structural changes and explore exactly where in the brain these changes occur as well as the underlying substrates of the changes including neural, glial, and vasculature components. Aerobic activity has been shown to produce different types of changes in the brain. The presence of novel experiences or learning is an especially important component in how these changes are manifest. We also discuss the distinct time courses of structural brain changes with both aerobic activity and learning as well as how these effects might differ in diseased and elderly groups.

Thomas, Adam G.; Dennis, Andrea; Bandettini, Peter A.; Johansen-Berg, Heidi

2011-01-01

295

Transient oxygen-glucose deprivation causes immediate changes in redox activity in mouse brain tissue.  

PubMed

Redox activity is an important property of living cells, and decreases in redox activity are likely to be an upstream event in ischemic brain injuries. In this study, immediate changes in redox activity caused by ischemic injury were investigated in oxygen-glucose deprivation (OGD) treated mouse brain tissue. Adult mouse brain slices were subjected to 10 min or 15 min OGD treatments and were immediately stained with an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) staining procedure. After 10 min OGD, the redox activity decreased in the lateral globus pallidus (LGP), medial globus pallidus (MGP), pyramidal cell layer of hippocampus CA1 (CA1(PL)) and the granular layer of the cerebellum (cereb(GL)). After 15 min OGD, decreases also occurred in the substantia nigra (SN) and several other areas of the brain stem. Hoechst 33342 was used to confirm that changes in redox activity occurred before morphological alterations in the cellular nuclei--morphological changes were not observed even after a 60 min OGD. The results presented here indicate that functional ischemic vulnerability exists in several brain regions, and will be helpful for systematic research on mammalian brain injury caused by transient metabolic stress. PMID:21414304

Chen, Lianwan; Bai, Shuyun; Su, Wenting; Song, Xueqin; Zhang, Peng; Li, Li; Ji, Juan Juan

2011-03-15

296

Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with ?-amyloid plaque pathology  

Microsoft Academic Search

Cholinergic deficits in Alzheimer’s disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether ?-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5

Margrit Klingner; Jenny Apelt; Ashok Kumar; Dietlind Sorger; Osama Sabri; Jörg Steinbach; Matthias Scheunemann; Reinhard Schliebs

2003-01-01

297

Altered cell calcium regulation in synaptosomes and brain cells of the 30-month-old rat: Prominent effects in hippocampus  

Microsoft Academic Search

A deficient regulation of neuronal cytosolic calcium levels has been suggested to play a role in the pathogenesis of neurodegeneration. However, evidence for an alteration in cytosolic calcium regulation in old age is at present controversial. The present work was aimed at studying whether changes in synaptosomal calcium homeostasis in 30-month-old rats are uniform throughout the brain or affect specific

Martin Villalba; Rodolfo Pereira; Alberto Martínez-Serrano; Jorgina Satrústegui

1995-01-01

298

ASSESSMENT OF CHEMICALLY-INDUCED ALTERATIONS IN BRAIN DEVELOPMENT USING ASSAYS OF NEURON- AND GLIA-LOCALIZED PROTEINS  

EPA Science Inventory

Chemical intervention during prenatal or postnatal ontogeny can result in complex biochemical, morphological and behavioral alterations in brain development (Suzuki, 1980; Miller and O'Callaghan, 1984; Rodier, 1986; Ruppert, 1986). s has been shown at this conference (e.g. by Ham...

299

Lack of Alteration in Regional Brain Adenosine 3',5'-Cyclic Monophosphate Levels after Acute and Chronic Treatment with Ethanol.  

National Technical Information Service (NTIS)

Previously reported studies have suggested that acute and chronic treatment with ethanol induces alterations in adenosine 3-5-cyclic monophosphate (C-AMP) levels in the brain. Because the methods used to minimize postmortem accumulation of C-AMP are now c...

J. D. Redos W. A. Hunt G. N. Catravas

1976-01-01

300

Altered Small-World Efficiency of Brain Functional Networks in Acupuncture at ST36: A Functional MRI Study  

PubMed Central

Background Acupuncture in humans can produce clinical effects via the central nervous system. However, the neural substrates of acupuncture’s effects remain largely unknown. Results We utilized functional MRI to investigate the topological efficiency of brain functional networks in eighteen healthy young adults who were scanned before and after acupuncture at the ST36 acupoints (ACUP) and its sham point (SHAM). Whole-brain functional networks were constructed by thresholding temporal correlations matrices of ninety brain regions, followed by a graph theory-based analysis. We showed that brain functional networks exhibited small-world attributes (high local and global efficiency) regardless of the order of acupuncture and stimulus points, a finding compatible with previous studies of brain functional networks. Furthermore, the brain networks had increased local efficiency after ACUP stimulation but there were no significant differences after SHAM, indicating a specificity of acupuncture point in coordinating local information flow over the whole brain. Moreover, significant (P<0.05, corrected by false discovery rate approach) effects of only acupuncture point were detected on nodal degree of the left hippocampus (higher nodal degree at ACUP as compared to SHAM). Using an uncorrected P<0.05, point-related effects were also observed in the anterior cingulate cortex, frontal and occipital regions while stimulation-related effects in various brain regions of frontal, parietal and occipital cortex regions. In addition, we found that several limbic and subcortical brain regions exhibited point- and stimulation-related alterations in their regional homogeneity (P<0.05, uncorrected). Conclusions Our results suggest that acupuncture modulates topological organization of whole-brain functional brain networks and the modulation has point specificity. These findings provide new insights into neuronal mechanism of acupuncture from the perspective of functional integration. Further studies would be interesting to apply network analysis approaches to study the effects of acupuncture treatments on brain disorders.

Liu, Xian; Duan, Xiaohui; Shang, Xiaojing; Long, Yu; Chen, Zhiguang; Li, Xiaofang; Huang, Yan; He, Yong

2012-01-01

301

[Alterations in erythrocyte membrane. Effect of neutrophil activation].  

PubMed

White blood cells, especially polymorphonuclear neutrophils (PMN), are known to alter some hemorheological parameters. Most of in vitro results have been obtained with passive PMN. Stimulated PMN also lead to other hemorheological changes. In our study, we have firstly activated PMN with opsonized zymosan and collected a PMN-free supernatant after 30 minutes activation. This supernatant was secondarily incubated with erythrocytes either in whole blood or in suspension. After 10 minutes incubation, hemorheological parameters were evaluated: 1) red blood deformability (RBC) (Ektacytometer* Technicon), 2) RBC filtration (Hemorheometer MK 1), 3) RBC aggregation (Erythroaggregometer* Sefam), 4) Plasmatic and whole blood viscosities (Low Shear 30* Contraves). Our results show that activated PMN-supernatant increases rigidity index (IR) of RBC in suspensions (IR of RBC control = 14.59 +/- 3.30 towards RI of incubated RBC = 22.91 +/- 7.06 p less than 0.001). Other rheological parameters remain unchanged. Activated PMN suspenatant influence on RBC is slight but could suggest of an alteration of RBC membrane. With an in vitro model of washed platelets aggregation, we have previously demonstrated that proaggregant activity of PMN supernatant was inhibited by specific Platelet-Activating Factor (PAF-acether) antagonists: BN 52021, BN 50723, Web 2086. We have so compared both effects of activated PMN-supernatant and synthetic PAF-acether on RBC membrane fluidity. Membrane fluidity was studied by fluorescence polarization of 4 probes embedded at different deep in the membrane of intact RBC. Similar modifications of RBC membrane fluidity are observed with either synthetic PAF-acether or PMN supernatant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1940654

Petitfrere, E; Nguyen, P; Mailliot, J L; Culioli-Pickel, B; Potron, G

1991-01-01

302

Stress-Induced Asymmetric Frontal Brain Activity and Aggression Risk  

Microsoft Academic Search

Impersonal stressors, not only interpersonal provocation, can instigate aggression through an associative network linking negative emotions to behavioral activation (L. Berkowitz, 1990). Research has not examined the brain mechanisms that are engaged by different types of stress and serve to promote hostility and aggression. The present study examined whether stress exposure elicits more left than right frontal brain activity implicated

Edelyn Verona; Naomi Sadeh; John J. Curtin

2009-01-01

303

Language-related brain activity revealed by independent component analysis  

Microsoft Academic Search

Objective: When an individual engages in a cognitive task, a multitude of diverse processes are activated in his\\/her brain and it is reasonable to assume that multiple brain sources are simultaneously active at any one time. Magnetoencephalographic (MEG) data recorded in such circumstances provide a picture of spatial distribution and time course of the sum of the magnetic fields generated

Carlo Salustri; Eugene Kronberg

304

Language-related brain activity revealed by independent component analysis  

Microsoft Academic Search

Objective: When an individual engages in a cognitive task, a multitude of diverse processes are activated in his\\/her brain and it is reasonable to assume that multiple brain sources are simultaneously active at any one time. Magnetoencephalographic (MEG) data recorded in such circumstances provide a picture of spatial distribution and time course of the sum of the magnetic fields generated

Carlo Salustri; Eugene Kronberg

2004-01-01

305

Activation of a mobile robot through a brain computer interface  

Microsoft Academic Search

This work presents the development of a brain computer interface as an alternative communication channel to be used in Robotics. It encompasses the implementation of an electroencephalograph (EEG), as well as the development of all computational methods and necessary techniques to identify mental activities. The developed brain computer interface (BCI) is applied to activate the movements of a 120lb mobile

Alexandre Ormiga Galvão Barbosa; David Ronald Achanccaray; Marco A. Meggiolaro

2010-01-01

306

Altered expression pattern of testican-1 mRNA after brain injury.  

PubMed

Testican, a chondroitin/heparan sulfate proteoglycan, is primarily expressed in neurons of the adult and embryonic mouse brain, suggesting its role in normal and/or proliferation and differentiation processes of neurons. However, the role of testican in injured brain remains unclear. In the present study we investigated testican-1 mRNA expression pattern after cryo-injury of the brain. In situ hybridization histochemistry revealed that testican-1 mRNA is induced in the region surrounding the necrotic tissue. Time course study of testican-1 mRNA showed the highest level of signal intensity at 7 days after the injury. To determine which cell types express testican-1 mRNA, we performed in situ hybridization histochemistry combined with immunohistochemistry of several cell markers. Testican-1 mRNA signals were detected in the proximal reactive astrocytes, whereas the distribution pattern of testican-1 mRNA positive cells was different from those of mature oligodendrocytes and activated microglia. In addition, signals for testican-1 mRNA overlapped with those of FGF-2 mRNA, showing that these molecules are coexpressed in reactive astrocytes. These results suggest a possibility that testican-1 plays a permissive role for regenerating axons in reactive astrocytes after injury. PMID:22199127

Iseki, Ken; Hagino, Seita; Zhang, Yuxiang; Mori, Tetsuji; Sato, Nobuko; Yokoya, Sachihiko; Hozumi, Yasukazu; Goto, Kaoru; Tase, Choichiro

2011-12-01

307

Altered brain connectivity in 3-to 7-year-old children with autism spectrum disorder.  

PubMed

Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity and/or aberrant hemispheric lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, the physiological connectivity of the brain in young children with ASD under conscious conditions has not yet been described. Magnetoencephalography (MEG) is a noninvasive brain imaging technique that is practical for use in young children. MEG produces a reference-free signal and is, therefore, an ideal tool for computing the coherence between two distant cortical rhythms. Using a custom child-sized MEG, we recently reported that 5- to 7-year-old children with ASD (n = 26) have inherently different neural pathways than typically developing (TD) children that contribute to their relatively preserved performance of visual tasks. In this study, we performed non-invasive measurements of the brain activity of 70 young children (3-7 years old, of which 18 were aged 3-4 years), a sample consisting of 35 ASD children and 35 TD children. Physiological connectivity and the laterality of physiological connectivity were assessed using intrahemispheric coherence for 9 frequency bands. As a result, significant rightward connectivity between the parietotemporal areas, via gamma band oscillations, was found in the ASD group. As we obtained the non-invasive measurements using a custom child-sized MEG, this is the first study to demonstrate a rightward-lateralized neurophysiological network in conscious young children (including children aged 3-4 years) with ASD. PMID:24179793

Kikuchi, Mitsuru; Shitamichi, Kiyomi; Yoshimura, Yuko; Ueno, Sanae; Hiraishi, Hirotoshi; Hirosawa, Tetsu; Munesue, Toshio; Nakatani, Hideo; Tsubokawa, Tsunehisa; Haruta, Yasuhiro; Oi, Manabu; Niida, Yo; Remijn, Gerard B; Takahashi, Tsutomu; Suzuki, Michio; Higashida, Haruhiro; Minabe, Yoshio

2013-03-19

308

Alterations in Prefrontal-Limbic Functional Activation and Connectivity in Chronic Stress-Induced Visceral Hyperalgesia  

PubMed Central

Repeated water avoidance stress (WAS) induces sustained visceral hyperalgesia (VH) in rats measured as enhanced visceromotor response to colorectal distension (CRD). This model incorporates two characteristic features of human irritable bowel syndrome (IBS), VH and a prominent role of stress in the onset and exacerbation of IBS symptoms. Little is known regarding central mechanisms underlying the stress-induced VH. Here, we applied an autoradiographic perfusion method to map regional and network-level neural correlates of VH. Adult male rats were exposed to WAS or sham treatment for 1 hour/day for 10 days. The visceromotor response was measured before and after the treatment. Cerebral blood flow (CBF) mapping was performed by intravenous injection of radiotracer ([14C]-iodoantipyrine) while the rat was receiving a 60-mmHg CRD or no distension. Regional CBF-related tissue radioactivity was quantified in autoradiographic images of brain slices and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. Compared to sham rats, stressed rats showed VH in association with greater CRD-evoked activation in the insular cortex, amygdala, and hypothalamus, but reduced activation in the prelimbic area (PrL) of prefrontal cortex. We constrained results of seed correlation analysis by known structural connectivity of the PrL to generate structurally linked functional connectivity (SLFC) of the PrL. Dramatic differences in the SLFC of PrL were noted between stressed and sham rats under distension. In particular, sham rats showed negative correlation between the PrL and amygdala, which was absent in stressed rats. The altered pattern of functional brain activation is in general agreement with that observed in IBS patients in human brain imaging studies, providing further support for the face and construct validity of the WAS model for IBS. The absence of prefrontal cortex-amygdala anticorrelation in stressed rats is consistent with the notion that impaired corticolimbic modulation acts as a central mechanism underlying stress-induced VH.

Wang, Zhuo; Ocampo, Marco A.; Pang, Raina D.; Bota, Mihail; Bradesi, Sylvie; Mayer, Emeran A.; Holschneider, Daniel P.

2013-01-01

309

Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain  

PubMed Central

Eight-hydroxy-2?-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer’s disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activities in nuclear and mitochondrial fractions from frontal (FL), temporal (TL), and parietal (PL) lobes from 8 MCI and 7 LAD patients, and 6 age-matched normal control (NC) subjects. OGG1 activity was significantly (P<0.05) decreased in nuclear specimens of FL, TL, and PL in MCI and LAD and in mitochondria from LAD FL and TL and MCI TL. Nuclear OGG1 protein was significantly decreased in LAD FL and MCI and LAD PL. No differences in mitochondrial OGG1 protein levels were found. Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD.

Shao, Changxing; Xiong, Shuling; Li, Guo-Min; Gu, Liya; Mao, Guogen; Markesbery, William R.; Lovell, Mark A.

2009-01-01

310

Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats.  

PubMed

The present study is designed to screen the possible effects of sodium orthovanadate therapy on the kinetic parameters of brain membrane-bound and soluble acetylcholinesterase (AChE) forms in alloxan-induced diabetic rats. The diabetic rats were treated with 300 mg/kg sodium orthovanadate orally for 45 days. While diabetes significantly decreased the brain specific activity (V(max)) of AChE soluble form by 42%, it caused a fivefold increase of the K(m) of the membrane-bound form. Furthermore, the activity of brain glutathione-S-transferase (GST) was significantly decreased and this was associated with a remarkable increase in brain lipid peroxidative parameter, thiobarbituric acid reactive substances (TBARS), as compared to sham control. The alterations of both AChE forms observed in diabetic state could be attributed to hyperglycemia and lipid peroxidation that triggered brain dysfunction by disturbing the neurotransmitter acetylcholine level. Administration of sodium orthovanadate reversed the diabetic conditions by lowering the blood glucose level and normalized the blood Hb(A1C) level. It also normalized the levels of brain AChE, GST and TBARS as compared to diabetic state and control. Therefore, vanadate administration could protect against direct action of lipid peroxidation on brain AChE and in this way, it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes. PMID:18378083

Ghareeb, Doaa A; Hussen, Hend M

2008-03-18

311

HYPERTENSION INDUCES BRAIN ?-AMYLOID ACCUMULATION, COGNITIVE IMPAIRMENT AND MEMORY DETERIORATION THROUGH ACTIVATION OF RAGE IN BRAIN VASCULATURE  

PubMed Central

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer’s Disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by Transverse Aortic Constriction, leading to alterations typical of Alzheimer’s Disease, such as amyloid plaques, neuroinflammation, Blood Brain Barrier dysfunction and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer’s Disease of hypertensive mice. We focused on RAGE, that critically regulates A? transport at the Blood Brain Barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE up-regulation in brain vessels of cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal A? deposition. The increased RAGE expression in TAC mice was induced by increased circulating AGEs and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an AGEs inhibitor or antioxidant prevented the development of Alzheimer’s traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal A? deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer’s Disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer.

Carnevale, Daniela; Mascio, Giada; D'Andrea, Ivana; Fardella, Valentina; Bell, Robert D.; Branchi, Igor; Pallante, Fabio; Zlokovic, Berislav; Yan, Shirley ShiDu; Lembo, Giuseppe

2012-01-01

312

Relationships between Brain Activation and Brain Structure in Normally Developing Children  

PubMed Central

Dynamic changes in brain structure, activation, and cognitive abilities co-occur during development, but little is known about how changes in brain structure relate to changes in cognitive function or brain activity. By using cortical pattern matching techniques to correlate cortical gray matter thickness and functional brain activity over the entire brain surface in 24 typically developing children, we integrated structural and functional magnetic resonance imaging data with cognitive test scores to identify correlates of mature performance during orthographic processing. Fast-naming individuals activated the right fronto-parietal attention network in response to novel fonts more than slow-naming individuals, and increased activation of this network was correlated with more mature brain morphology in the same fronto-parietal region. These relationships remained even after effects of age or general cognitive ability were statistically controlled. These results localized cortical regions where mature morphology corresponds to mature patterns of activation, and may suggest a role for experience in mediating brain structure–activation relationships.

Lu, Lisa H.; Dapretto, Mirella; O'Hare, Elizabeth D.; Kan, Eric; McCourt, Sarah T.; Thompson, Paul M.; Toga, Arthur W.; Bookheimer, Susan Y.

2009-01-01

313

Expression of fatty acid binding proteins is altered in aged mouse brain  

Microsoft Academic Search

Brain membrane lipid fatty acid composition and consequently membrane fluidity change with increasing age. Intracellular fatty acid binding proteins (FABPs) such as heart H-FABP and the brain specific B-FABP, detected by immunoblotting of brain tissue, are thought to be involved in fatty acid uptake, metabolism, and differentiation in brain. Yet, almost nothing is known regarding the effect of age on

Lixia Pu; Urule Igbavboa; Gibson Wood; John B. Roths; A. B. Kier; Friedrich Spener; Friedhelm Schroeder

1999-01-01

314

Brain region-specific altered expression and association of mitochondria-related genes in autism  

PubMed Central

Background Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. Methods For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (??Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Results Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients. Conclusions Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted.

2012-01-01

315

Brain and Bone Damage in KARAP/DAP12 Loss-of-Function Mice Correlate with Alterations in Microglia and Osteoclast Lineages  

PubMed Central

Human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease, has been described to be associated with mutations affecting the immunoreceptor tyrosine-based activation motif-bearing KARAP/DAP12 immunoreceptor gene. Patients present bone fragilities and severe neurological alterations leading to presenile dementia. Here we investigated whether the absence of KARAP/DAP12-mediated signals in loss-of-function (K?75) mice also leads to bone and central nervous system pathological features. Histological analysis of adult K?75 mice brains revealed a diffuse hypomyelination predominating in anterior brain regions. As this was not accompanied by oligodendrocyte degeneration or microglial cell activation it suggests a developmental defect of myelin formation. Interestingly, in postnatal K?75 mice, we observed a dramatic reduction in microglial cell numbers similar to in vitro microglial cell differentiation impairment. Our results raise the intriguing possibility that defective microglial cell differentiation might be responsible for abnormal myelin development. Histomorphometry revealed that bone remodeling is also altered, because of a resorption defect, associated with a severe block of in vitro osteoclast differentiation. In addition, we show that, among monocytic lineages, KARAP/DAP12 specifically controls microglial and osteoclast differentiation. Our results confirm that KARAP/DAP12-mediated signals play an important role in the regulation of both brain and bone homeostasis. Yet, important differences exist between the symptoms observed in Nasu-Hakola patients and K?75 mice.

Nataf, Serge; Anginot, Adrienne; Vuaillat, Carine; Malaval, Luc; Fodil, Nassima; Chereul¶, Emmanuel; Langlois¶, Jean-Baptiste; Dumontel, Christiane; Cavillon, Gaelle; Confavreux, Christian; Mazzorana, Marlene; Vico, Laurence; Belin, Marie-Franacoise; Vivier, Eric; Tomasello, Elena; Jurdic, Pierre

2005-01-01

316

Expression of astrocytic markers aquaporin 4 and connexin 43 is altered in brains of subjects with autism.  

PubMed

Neuroanatomical studies have revealed extensive structural brain abnormalities in subjects with autism. Recently, studies have provided evidence of neuroglial responses and neuroinflammation in autism. The current study investigated whether two astrocytic markers, aquaporin 4 and connexin 43, are altered in brains from subjects with autism. Postmortem brain tissues from Brodmann's Area 40 (BA40, parietal cortex), Brodmann's Area 9 (BA9, superior frontal cortex), and cerebella of subjects with autism and matched controls were subject to SDS-PAGE and western blotting. Connexin 43 expression was increased significantly in BA9. Aquaporin 4 expression was decreased significantly in cerebellum. These data suggest that changes are apparent in markers for abnormal glial-neuronal communication (connexin 43 and aquaporin 4) in brains of subjects with autism. PMID:18435417

Fatemi, S Hossein; Folsom, Timothy D; Reutiman, Teri J; Lee, Susanne

2008-07-01

317

Alterations in brain 5-hydroxy-tryptamine metabolism during the `withdrawal' phase after chronic treatment with diazepam and bromazepam  

PubMed Central

1 Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid-brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid-brain region of rats subjected to benzodiazepine treatment. 2 Chronic therapy with either of the two anti-anxiety agents enhanced the endogenous levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons-medulla, mid-brain and striatum. 3 Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid-brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5-hydroxy-indoleacetic acid levels is not associated with enhanced deamination of 5-hydroxytryptamine. 4 Discontinuation of treatment for 48 h significantly decreased the activity of mid-brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine-treated and normal rats. The concentrations of mid-brain tryptophan and 5-hydroxytryptamine were also reduced in various brain regions examined. 5 Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5-hydroxyindoleacetic acid. 6 The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5-hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine.

Agarwal, R.A.; Lapierre, Y.D.; Rastogi, R.B.; Singhal, R.L.

1977-01-01

318

Altered amygdala activation in schizophrenia patients during emotion processing.  

PubMed

Dysfunctional emotion processing in patients suffering from schizophrenia is a prominent clinical feature of great importance for social functioning and subjective well-being. The neurobiological underpinnings are still poorly understood. Here we investigated a large sample of schizophrenia patients and matched healthy controls with an event-related fMRI task during emotion processing using emotional pictures from the International Affective Picture System (IAPS). Schizophrenia patients revealed stronger right amygdala activation during negative and attenuated response during positive affective picture processing compared to healthy controls. Further analysis indicated that medication status influences activation of the ventral anterior cingulate cortex during negative affective stimuli processing. These results might represent a correlate of altered emotional experience in schizophrenia patients who are known to report less positive and more negative affective states in daily life situations. PMID:23911256

Pankow, Anne; Friedel, Eva; Sterzer, Philipp; Seiferth, Nina; Walter, Henrik; Heinz, Andreas; Schlagenhauf, Florian

2013-08-02

319

Brain Activation during Working Memory after Traumatic Brain Injury in Children  

Microsoft Academic Search

Eight children with moderate to severe traumatic brain injury (TBI) and eight matched, uninjured control children underwent fMRI during an N-back task to test effects of TBI on working memory performance and brain activation. Two patterns in the TBI group were observed. Patients whose criterion performance was reached at lower memory loads than control children demonstrated less extensive frontal and

Mary R. Newsome; Randall S. Scheibel; Jill V. Hunter; Zhiyue J. Wang; Zili Chu; Xiaoqi Li; Harvey S. Levin

2007-01-01

320

Insulin-like growth factors and binding proteins in the fetal rat: Alterations during maternal starvation and effects in fetal brain cell culture  

Microsoft Academic Search

Maternal malnutrition adversely affects fetal body and brain growth during late gestation. We utilized a fetal brain cell culture model to examine whether alternations in circulating factors may contribute to reduce brain growth during maternal starvation; we then used specific immunoassay and western blotting techniques, and purified peptides to investigate the potential role that altered levels of insulin-like growth factors

G. E. Shambaugh; J. A. Radosevich; R. P. Glick; D. S. Gu; B. E. Metzger; T. G. Unterman

1993-01-01

321

Brain activity of women is more fractal than men.  

PubMed

Investigating gender differences of the brain is of both scientific and clinical importance, as understanding such differences may be helpful for improving gender specific treatments of neuropsychiatric disorders. As brain is a highly complex system, it is crucial to investigate its activity in terms of nonlinear dynamics. However, there are few studies that investigated gender differences based on dynamical characteristics of the brain. Fractal dimension (FD) is a key characteristic of the brain dynamics which indicates the level of complexity on which the neuronal regions function or interact and quantifies the associated brain processes on a scale ranging from fully deterministic to fully random. This study investigates the gender differences of brain dynamics, comparing fractal dimension of scalp EEGs (in eyes-closed resting state) of 34 female and 34 male healthy adults. The results showed significantly greater FDs in females compared to males in all brain regions except in lateral and occipital lobes. This indicates a higher complexity of the brain dynamics in females relative to males. The high accuracies of 87.8% and 93.1% obtained by logistic regression and enhanced probabilistic neural network, respectively, in discriminating between the gender groups based on the FDs also confirmed the great gender differences of complexity of brain activities. The results showed that delta, alpha, and beta bands are the frequency bands that contribute most to the gender differences in brain complexity. Furthermore, the lateralization analysis showed the leftward lateralization of complexity in females is greater than in males. PMID:23313595

Ahmadi, Khodabakhsh; Ahmadlou, Mehran; Rezazade, Majid; Azad-Marzabadi, Esfandiar; Sajedi, Firoozeh

2013-01-08

322

Effects of a carbohydrate supplement upon resting brain activity  

Microsoft Academic Search

Glucose is a major energy source for the brain, and along with several monosaccharide derivatives as components of brain gangliosides,\\u000a they play important roles in neurologic function. However, there is little information available on the role of glucose and\\u000a other monosaccharides on resting brain activity. This study was designed to evaluate the effects of a single dose of a carbohydrate

Chenghua Wang; Joanne S. Szabo; Roscoe A. Dykman

2004-01-01

323

VAP-1\\/SSAO Plasma Activity and Brain Expression in Human Hemorrhagic Stroke  

Microsoft Academic Search

Background: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme that belongs to the semicarbazide-sensitive amine oxidase (SSAO) family, which oxidatively deaminates primary amines and is implicated in leukocyte extravasation. Our aim was to investigate the alteration of soluble VAP-1\\/SSAO activity in plasma samples after acute intracerebral hemorrhage (ICH) and its presence in human ICH brain tissue. Methods:

Mar Hernandez-Guillamon; Montse Solé; Pilar Delgado; Lidia García-Bonilla; Dolors Giralt; Cristina Boada; Anna Penalba; Sandra García; Alan Flores; Marc Ribó; José Alvarez-Sabin; Arantxa Ortega-Aznar; Mercedes Unzeta; Joan Montaner

2012-01-01

324

Motivational influences on cognitive control: Behavior, brain activation, and individual differences  

Microsoft Academic Search

What changes in brain activity are associated with changes in motivational state? The present study addressed this question\\u000a by having participants perform a cognitive task (AX variant of the Continuous Performance Test; AX-CPT) under three different\\u000a blocked motivational conditions (reward-incentive, penalty-incentive, and baseline). Behavioral data showed that the incentive\\u000a conditions modulated task performance, potentially by altering participants’ cognitive control strategy.

Hannah S. Locke; Todd S. Braver

2008-01-01

325

Altered Topological Properties of Functional Network Connectivity in Schizophrenia during Resting State: A Small-World Brain Network Study  

PubMed Central

Aberrant topological properties of small-world human brain networks in patients with schizophrenia (SZ) have been documented in previous neuroimaging studies. Aberrant functional network connectivity (FNC, temporal relationships among independent component time courses) has also been found in SZ by a previous resting state functional magnetic resonance imaging (fMRI) study. However, no study has yet determined if topological properties of FNC are also altered in SZ. In this study, small-world network metrics of FNC during the resting state were examined in both healthy controls (HCs) and SZ subjects. FMRI data were obtained from 19 HCs and 19 SZ. Brain images were decomposed into independent components (ICs) by group independent component analysis (ICA). FNC maps were constructed via a partial correlation analysis of ICA time courses. A set of undirected graphs were built by thresholding the FNC maps and the small-world network metrics of these maps were evaluated. Our results demonstrated significantly altered topological properties of FNC in SZ relative to controls. In addition, topological measures of many ICs involving frontal, parietal, occipital and cerebellar areas were altered in SZ relative to controls. Specifically, topological measures of whole network and specific components in SZ were correlated with scores on the negative symptom scale of the Positive and Negative Symptom Scale (PANSS). These findings suggest that aberrant architecture of small-world brain topology in SZ consists of ICA temporally coherent brain networks.

Yu, Qingbao; Sui, Jing; Rachakonda, Srinivas; He, Hao; Gruner, William; Pearlson, Godfrey; Kiehl, Kent A.; Calhoun, Vince D.

2011-01-01

326

Hydrogen Peroxide Stimulates Activity and Alters Behavior in Drosophila melanogaster  

PubMed Central

Circadian rhythms in animals are regulated at the level of individual cells and by systemic signaling to coordinate the activities of multiple tissues. The circadian pacemakers have several physiological outputs, including daily locomotor rhythms. Several redox-active compounds have been found to function in regulation of circadian rhythms in cells, however, how particular compounds might be involved in regulating specific animal behaviors remains largely unknown. Here the effects of hydrogen peroxide on Drosophila movement were analyzed using a recently developed three-dimensional real-time multiple fly tracking assay. Both hydrogen peroxide feeding and direct injection of hydrogen peroxide caused increased adult fly locomotor activity. Continuous treatment with hydrogen peroxide also suppressed daily locomotor rhythms. Conditional over-expression of the hydrogen peroxide-producing enzyme superoxide dismutase (SOD) also increased fly activity and altered the patterns of locomotor activity across days and weeks. The real-time fly tracking system allowed for detailed analysis of the effects of these manipulations on behavior. For example, both hydrogen peroxide feeding and SOD over-expression increased all fly motion parameters, however, hydrogen peroxide feeding caused relatively more erratic movement, whereas SOD over-expression produced relatively faster-moving flies. Taken together, the data demonstrate that hydrogen peroxide has dramatic effects on fly movement and daily locomotor rhythms, and implicate hydrogen peroxide in the normal control of these processes.

Grover, Dhruv; Ford, Daniel; Brown, Christopher; Hoe, Nicholas; Erdem, Aysen; Tavare, Simon; Tower, John

2009-01-01

327

Ethanol-induced alterations in sup 14 C-glucose utilization: Modulation by brain adenosine in mice  

SciTech Connect

The possible role of brain adenosine (Ado) in acute ethanol-induced alteration in glucose utilization in the cerebellum and brain stem was investigated. The slices were incubated for 100 min in a glucose medium in Warburg flasks using {sup 14}C-glucose as a tracer. Trapped {sup 14}CO{sub 2} was counted to estimate glucose utilization. Ethanol markedly increased the glucose utilization in both areas of brain. Theophylline, an Ado antagonist, significantly reduced ethanol-induced increase in glucose utilization in both brain areas. Ado agonist CHA significantly accentuated ethanol-induced increase in glucose utilization in both motor areas. Ado agonist CHA significantly accentuated ethanol-induced increase in glucose utilization in both motor areas. Ethanol was still able to produce a smaller but significant increase in glucose utilization in both brain areas when theophylline and CHA were given together, suggesting an additional mechanism. Collectively, the data indicate that ethanol-induced glucose utilization in the cerebellum and brain stem is modulated by brain Ado receptor and by non-adenosinergic mechanism.

Anwer, J.; Dar, M.S. (East Carolina Univ., Greenville, NC (United States))

1992-02-26

328

Human immunodeficiency virus glycoproteins 160 and 41 alter sleep and brain temperature of rats  

Microsoft Academic Search

Sleep is altered during all stages at which it has been recorded during chronic human immunodeficiency virus (HIV) infection, including the long latent phase before the development of AIDS; the mechanisms for such alterations are not known. The HIV envelope glycoprotein (gp) 120 alters sleep of rats in a manner somewhat similar to the alterations that occur in humans infected

C Gemma; M. R Opp

1999-01-01

329

Evoked Brain Activity and Personnel Performance.  

National Technical Information Service (NTIS)

Prior research has suggested that brain recordings such as the neuroelectric evoked potential (EP) and neuromagnetic fields may substantially augment personnel assessment procedures. Such procedures include the measurement and prediction of on-job perform...

G. W. Lewis R. C. Sorenson

1987-01-01

330

Brain activation during mental rotation in school children and adults  

Microsoft Academic Search

Summary  Mental rotation is a complex cognitive skill depending on the manipulation of mental representations. We aimed to investigate\\u000a the maturing neuronal network for mental rotation by measuring brain activation in 20 children and 20 adults using functional\\u000a magnetic resonance imaging. Our results indicate that brain activation patterns are very similar between children and adults.\\u000a However, adults exhibit stronger activation in

K. Kucian; M. von Aster; T. Loenneker; T. Dietrich; F. W. Mast; E. Martin

2007-01-01

331

Cannabis use and brain structural alterations of the cingulate cortex in early psychosis.  

PubMed

As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors. PMID:24054726

Rapp, Charlotte; Walter, Anna; Studerus, Erich; Bugra, Hilal; Tamagni, Corinne; Röthlisberger, Michel; Borgwardt, Stefan; Aston, Jacqueline; Riecher-Rössler, Anita

2013-09-18

332

Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain  

SciTech Connect

The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism.

Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

1986-03-05

333

Transcriptional signature of an adult brain tumor in Drosophila  

Microsoft Academic Search

BACKGROUND: Mutations and gene expression alterations in brain tumors have been extensively investigated, however the causes of brain tumorigenesis are largely unknown. Animal models are necessary to correlate altered transcriptional activity and tumor phenotype and to better understand how these alterations cause malignant growth. In order to gain insights into the in vivo transcriptional activity associated with a brain tumor,

Thomas Loop; Ronny Leemans; Urs Stiefel; Leandro Hermida; Boris Egger; Fukang Xie; Michael Primig; Ulrich Certa; Karl-Friedrich Fischbach; Heinrich Reichert; Frank Hirth

2004-01-01

334

Brain activity and desire for Internet video game play  

Microsoft Academic Search

ObjectiveRecent studies have suggested that the brain circuitry mediating cue-induced desire for video games is similar to that elicited by cues related to drugs and alcohol. We hypothesized that desire for Internet video games during cue presentation would activate similar brain regions to those that have been linked with craving for drugs or pathologic gambling.

Doug Hyun Han; Nicolas Bolo; Melissa A. Daniels; Lynn Arenella; In Kyoon Lyoo; Perry F. Renshaw

2011-01-01

335

Stress in Pregnancy Activates Neurosteroid Production in the Fetal Brain  

Microsoft Academic Search

Neurosteroids such as allopregnanolone are potent agonists at the GABAA receptor and suppress the fetal CNS activity. These steroids are synthesized in the fetal brain either from cholesterol or from circulating precursors derived from the placenta. The concentrations of allopregnanolone are remarkably high in the fetal brain and rise further in response to acute hypoxic stress, induced by constriction of

Jonathan J. Hirst; Tamara Yawno; Phuong Nguyen; David W. Walker

2006-01-01

336

Increased brain activation during verbal learning in obstructive sleep apnea  

Microsoft Academic Search

This study examined the cerebral response to a verbal learning (VL) task in obstructive sleep apnea (OSA) patients. Twelve OSA patients and 12 controls were studied with functional magnetic resonance imaging (FMRI). As hypothesized, VL performance was similar for both groups, but OSA patients showed increased brain activation in several brain regions. These regions included bilateral inferior frontal and middle

Liat Ayalon; Sonia Ancoli-Israel; Zoe Klemfuss; Mark D. Shalauta; Sean P. A. Drummond

2006-01-01

337

Changes in Brain Activity After a Diet-Induced Obesity  

Microsoft Academic Search

Compared to lean subjects, obese men have less activation in the dorsolateral prefrontal cortex, a brain area implicated in the inhibition of inappropriate behavior, satiety, and meal termination. Whether this deficit precedes weight gain or is an acquired feature of obesity remains unknown. An adult animal model of obesity may provide insight to this question since brain imaging can be

David Val-Laillet; Sabrina Layec; Sylvie Guérin; Paul Meurice; Charles-Henri Malbert

2011-01-01

338

Cardiovascular fitness modulates brain activation associated with spatial learning  

Microsoft Academic Search

Aerobic exercise has beneficial effects on cognitive functioning in aging humans, especially on executive functions associated with frontal brain regions. In rodents, exercise has been shown to induce structural and neurophysiological changes especially in the hippocampus and to improve spatial learning. The present study investigated the relationship between cardiovascular fitness, spatial learning and associated patterns of brain activation cross-sectionally and

Kathrin Holzschneider; Thomas Wolbers; Brigitte Röder; Kirsten Hötting

339

Functional MRI of brain activation evoked by intentional eye blinking  

Microsoft Academic Search

Eye blinking is not only a reflexive action to protect the ocular surface from injury and desiccation; it can also be done intentionally. However, only a few studies have investigated the brain mechanism controlling intentional blinking, and there are still inconsistencies among the reported activation patterns in the human brain evoked by intentional blinking. In monkeys, some areas where blinking

Makoto Kato; Satoru Miyauchi

2003-01-01

340

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.  

PubMed

Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, ?-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process. PMID:23911220

Das, Undurti N

2013-07-30

341

Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier  

PubMed Central

Background Defects in the low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein (Pgp) clearance of amyloid beta (A?) from brain are thought to contribute to Alzheimer’s disease (AD). We have recently shown that induction of systemic inflammation by lipopolysaccharide (LPS) results in impaired efflux of A? from the brain. The same treatment also impairs Pgp function. Here, our aim is to determine which physiological routes of A? clearance are affected following systemic inflammation, including those relying on LRP-1 and Pgp function at the blood–brain barrier. Methods CD-1 mice aged between 6 and 8?weeks were treated with 3 intraperitoneal injections of 3?mg/kg LPS at 0, 6, and 24 hours and studied at 28 hours. 125I-A?1-42 or 125I-alpha-2-macroglobulin injected into the lateral ventricle of the brain (intracerebroventricular (ICV)) or into the jugular vein (intravenous (IV)) was used to quantify LRP-1-dependent partitioning between the brain vasculature and parenchyma and peripheral clearance, respectively. Disappearance of ICV-injected 14?C-inulin from brain was measured to quantify bulk flow of cerebrospinal fluid (CSF). Brain microvascular protein expression of LRP-1 and Pgp was measured by immunoblotting. Endothelial cell localization of LRP-1 was measured by immunofluorescence microscopy. Oxidative modifications to LRP-1 at the brain microvasculature were measured by immunoprecipitation of LRP-1 followed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine. Results We found that LPS: caused an LRP-1-dependent redistribution of ICV-injected A? from brain parenchyma to brain vasculature and decreased entry into blood; impaired peripheral clearance of IV-injected A?; inhibited reabsorption of CSF; did not significantly alter brain microvascular protein levels of LRP-1 or Pgp, or oxidative modifications to LRP-1; and downregulated LRP-1 protein levels and caused LRP-1 mislocalization in cultured brain endothelial cells. Conclusions These results suggest that LRP-1 undergoes complex functional regulation following systemic inflammation which may depend on cell type, subcellular location, and post-translational modifications. Our findings that systemic inflammation causes deficits in both A? transport and bulk flow like those observed in AD indicate that inflammation could induce and promote the disease.

2012-01-01

342

Brain tyrosine hydroxylase activity and calculated amount of brain dopa synthesized in carbon tetrachlorideintoxicated rats  

Microsoft Academic Search

Summary  Tyrosine hydroxylase activity in the corpus striatum was measured in a large dose of carbon tetrachloride (CCl4)-intoxicated rats in order to confirm whether brain catecholamine contents decrease in acute hepatic failure or not. Theoretical\\u000a amounts of dopa synthesized in the brain of the treated animals were calculated according to an equation of enzyme kinetics.\\u000a Tyrosine hydroxylase activities in CCl4-injured rats

Nobuyuki Takei; Akiharu Watanabe; Tatsuro Sakata; Shosaku Hayashi; Takahiro Obata; Tetsuya Shiota; Hideo Nagashima

1983-01-01

343

A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests  

PubMed Central

Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing improved treatments for mood disorders and other brain disorders with altered chromatin-mediated neuroplasticity.

Schroeder, Frederick A.; Lewis, Michael C.; Fass, Daniel M.; Wagner, Florence F.; Zhang, Yan-Ling; Hennig, Krista M.; Gale, Jennifer; Zhao, Wen-Ning; Reis, Surya; Barker, Douglas D.; Berry-Scott, Erin; Kim, Sung Won; Clore, Elizabeth L.; Hooker, Jacob M.; Holson, Edward B.; Haggarty, Stephen J.; Petryshen, Tracey L.

2013-01-01

344

Lipopolysaccharide alters the blood–brain barrier transport of amyloid ? protein: A mechanism for inflammation in the progression of Alzheimer’s disease  

Microsoft Academic Search

Alzheimer’s disease (AD) brains are characterized by accumulation of amyloid ? protein (A?) and neuroinflammation. Increased blood-to-brain influx and decreased brain-to-blood efflux across the blood–brain barrier (BBB) have been proposed as mechanisms for A? accumulation. Epidemiological studies suggest that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the progression of AD. We hypothesized that inflammation alters BBB handling of A?. Mice

Laura B. Jaeger; Shinya Dohgu; Rukhsana Sultana; Jessica L. Lynch; Joshua B. Owen; Michelle A. Erickson; Gul N. Shah; Tulin O. Price; Melissa A. Fleegal-Demotta; D. Allan Butterfiled; William A. Banks

2009-01-01

345

Viable mouse gene ablations that robustly alter brain A? levels are rare  

Microsoft Academic Search

BACKGROUND: Accumulation of amyloid-? (A?) peptide in the brain is thought to play a key pathological role in Alzheimer's disease. Many pharmacological targets have therefore been proposed based upon the biochemistry of A?, but not all are equally tractable for drug discovery. RESULTS: To search for novel targets that affect brain A? without causing toxicity, we screened mouse brain samples

Jeremy H Toyn; Xu-Alan Lin; Mark W Thompson; Valerie Guss; Jere E Meredith Jr; Sethu Sankaranarayanan; Nestor Barrezueta; John Corradi; Antara Majumdar; Daniel L Small; Melissa Hansard; Thomas Lanthorn; Ryan S Westphal; Charles F Albright

2010-01-01

346

Effects of a carbohydrate supplement upon resting brain activity.  

PubMed

Glucose is a major energy source for the brain, and along with several monosaccharide derivatives as components of brain gangliosides, they play important roles in neurologic function. However, there is little information available on the role of glucose and other monosaccharides on resting brain activity. This study was designed to evaluate the effects of a single dose of a carbohydrate supplement containing glucose and several of its derivatives on resting brain activity in 20 healthy male college students. The supplement provided an insignificant amount of carbohydrate (3.9 g), protein (0.28 g), fat (0 g), and calories (14 kcal). The amount of glucose in the supplement was 0.5 g (1% the amount of glucose used in adult studies of cognitive functioning and memory). We hypothesized that the glyconutrient supplement would enhance brain activity associated with alertness and attention. The study design was double blind, with subjects randomly assigned to one of two orders, either carbohydrate supplement week one followed by placebo a week later, or the opposite. Electrical brain activity was monitored by 15 electrodes positioned at nine standard international 10-20 system locations, including three bilateral pairs at frontal, parietal, and occipital sites. Thirty minutes following ingestion of a placebo or carbohydrate supplement drink, EEG activity was recorded for 10-mins while subjects focused on a stationary visual target. Spectral power of resting brain activity was computed and analyzed contrasting the placebo and supplement groups. Relative to placebo, the carbohydrate supplement significantly enhanced power in three brain wave frequencies (theta, alpha, and beta) that are known to be associated with attention and arousal. Since changes were observed in the supplement but not placebo group, our study suggests that additional sugars in the glyconutritional supplement facilitate enhancement of brain electrical activity. Whether the apparent enhancement of arousal in baseline recordings is associated with improved task performance remains to be determined. PMID:15759600

Wang, Chenghua; Szabo, Joanne S; Dykman, Roscoe A

347

Alterations of corticotropin-releasing factor-like immunoreactivity in different brain regions after acute cocaine administration in rats.  

PubMed

Corticotropin-releasing factor (CRF) may mediate some of the neuroendocrine and behavioral responses to cocaine. In this study, the distribution of CRF-like immunoreactivity (CRF-LI) was determined in the hypothalamus and in several extrahypothalamic brain regions after acute cocaine administration in handled rats. CRF-LI decreased dose-dependently with cocaine administration in the hypothalamus and in the basal-forebrain structures. A small dose of cocaine (7.5 mg/kg) decreased CRF-LI in the hippocampus and in the frontal cortex. A significant, selective, dose-dependent increase in CRF-LI was found in the amygdala after cocaine injection. None of the investigated doses of cocaine altered CRF-LI in the striatum. These results suggest that acute cocaine administration alters brain CRF systems to contribute behavioral and neuroendocrine responses to cocaine. PMID:8358623

Sarnyai, Z; Bíró, E; Gardi, J; Vecsernyés, M; Julesz, J; Telegdy, G

1993-07-01

348

Alteration of biophysical activity of pulmonary surfactant by aluminosilicate nanoparticles.  

PubMed

The influence of five different types of aluminosilicate nanoparticles (NPs) on the dynamic surface activity of model pulmonary surfactant (PS) (Survanta) was studied experimentally using oscillating bubble tensiometry. Bentonite, halloysite and montmorillonite (MM) NPs, which are used as fillers of polymer composites, were characterized regarding the size distribution, morphology and surface area. Particle doses applied in the studies were estimated based on the inhalation rate and duration, taking into account the expected aerosol concentration and deposition efficiency after penetration of NPs into the alveolar region. The results indicate that aluminosilicate NPs at concentrations in the pulmonary liquid above 0.1?mg?cm(-3) are capable of promoting alterations of the original dynamic biophysical activity of the PS. This effect is indicated by deviation of the minimum surface tension, stability index and the size of surface tension hysteresis. Such response is dependent on the type of NPs present in the system and is stronger when particle concentration increases. It is suggested that interactions between NPs and the PS must be related to the surfactant adsorption on the suspended particles, while in the case of surface-modified clay NPs the additional washout of surface-active components may be expected. It is speculated that observed changes in surface properties of the surfactant may be associated with undesired health effects following extensive inhalation of aluminosilicate NPs in the workplace. PMID:23363039

Kondej, Dorota; Sosnowski, Tomasz R

2013-02-01

349

Early-life experience alters response of developing brain to seizures  

PubMed Central

Prolonged seizures during childhood are associated with behavior problems, memory impairment and school failure. No effective treatment currently exists after seizures to mitigate neuronal injury and long-term neurological sequelae for children with epilepsy. We studied the therapeutic efficacy of early-life environment on seizure-induced behavioral deficits, neuronal injury and the inflammatory reaction using the kainic acid (KA) seizure model. Two rearing conditions, maternal separation for 3-hours daily versus maternal care in an enriched environment, were followed by single housing for the former (Deprived) and group housing in an enriched environment for the latter (Enriched). To examine the influence of differential rearing on the behavioral effects of early-life seizures, KA was injected on P21. On P28, marked reduction in exploratory behavior was noted after seizures only in the Deprived group. To investigate seizure-induced hippocampal injury, a separate group of rats were injected with KA on P35 since consistent seizure-induced neuronal injury is observed only in mature rats. Brains of rats sacrificed on P37 displayed a significant reduction in DNA fragmentation and microglial activation in Enriched compared to Deprived animals. Our results suggest that a nurturing early environment can enhance the ability of the developing brain to recover from seizures and provide a buffer against their damaging effects. While the nurturing environment was neuroprotective, the combination of deprived rearing and the insult of early-life seizures resulted in significant behavioral deficits, an increase in neuronal injury and activation of microglia in young rats.

Kazl, Cassandra; Foote, L. Tracy; Kim, Min-Jung; Koh, Sookyong

2009-01-01

350

Neonatal handling in eae-susceptible rats altersNGFlevels and mast cell distribution in the brain  

Microsoft Academic Search

Maternal separation in neonatal rodents causes a wide range of behaviouralandmetabolic alterations, affecting the physiological response of theneuro-immune-endocrinesystem. For example, interference with the normal mother-infantinteractions leads to anincreased susceptibility to experimentally-induced allergicencephalomyelitis (EAE) in adult life.Since it has been reported that mast cells (MCs) participatein the pathophysiology of theautoimmune inflammatory disease multiple sclerosis (MS) and alsoEAE and that brain nervegrowth

Luigi Manni; Alessandra Micera; Luana Pistillo; Luigi Aloe

1998-01-01

351

Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior  

Microsoft Academic Search

Depressive disorders are among the world's greatest public health problems. Na+, K+-ATPase is the established receptor for the steroidal digitalis-like compounds (DLC). Alteration in brain Na+, K+-ATPase and DLC have been detected in depressive disorders raising the hypothesis of their involvement in these pathology. The present study was designed to further elaborate this hypothesis by investigating the behavioral and biochemical

Inbal Goldstein; Elad Lax; Iris Gispan-Herman; Haim Ovadia; Haim Rosen; Gal Yadid; David Lichtstein

352

Harmful algal bloom toxins alter c-Fos protein expression in the brain of killifish, Fundulus heteroclitus  

Microsoft Academic Search

The immediate early gene c-fos, and its protein product c-Fos, are known to be induced in neurons of mammals and fish as a result of neuronal stimulation. The purpose of this study was to quantitatively examine CNS alterations in killifish, Fundulus heteroclitus, in relation to harmful algal bloom (HAB) toxin exposure. c-Fos expression was visualized using immunocytochemistry in the brains

J. D. Salierno; N. S. Snyder; A. Z. Murphy; M. Poli; S. Hall; D. Baden; A. S. Kane

2006-01-01

353

Age-dependent memory loss, synaptic pathology and altered brain plasticity in the Drosophila mutant cardinal accumulating 3-hydroxykynurenine  

Microsoft Academic Search

Summary.   A search for Drosophila mutants with phenotypes similar to human diseases might help to unravel evolutionary conserved genes\\u000a implicated in polygenic human disorders. Among these are neurodegenerative diseases, characterized by a late onset disturbance\\u000a of memory, synaptic and glial pathology, structural brain impairments and altered content of the intermediates of the kynurenine\\u000a pathway, the modulators of glutamate excito- and

E. Savvateeva; A. Popov; N. Kamyshev; J. Bragina; M. Heisenberg; D. Senitz; J. Kornhuber; P. Riederer

2000-01-01

354

Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques ( Macaca fascicularis )  

Microsoft Academic Search

Background  Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably\\u000a caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in\\u000a murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes\\u000a in ERV expression are a general phenomenon we used

Alex D Greenwood; Michelle Vincendeau; Ann-Christin Schmädicke; Judith Montag; Wolfgang Seifarth; Dirk Motzkus

2011-01-01

355

Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model  

Microsoft Academic Search

Individuals with 22q11.2 microdeletions show behavioral and cognitive deficits and are at high risk of developing schizophrenia. We analyzed an engineered mouse strain carrying a chromosomal deficiency spanning a segment syntenic to the human 22q11.2 locus. We uncovered a previously unknown alteration in the biogenesis of microRNAs (miRNAs) and identified a subset of brain miRNAs affected by the microdeletion. We

Kimberly L Stark; Bin Xu; Anindya Bagchi; Wen-Sung Lai; Hui Liu; Ruby Hsu; Xiang Wan; Paul Pavlidis; Alea A Mills; Maria Karayiorgou; Joseph A Gogos

2008-01-01

356

Maternal dietary choline availability alters the balance of netrin-1 and DCC neuronal migration proteins in fetal mouse brain hippocampus  

PubMed Central

Alterations in maternal dietary choline availability during days 12–17 of pregnancy led to an increase in the level of immunoreactive netrin-1 and a decrease in the level of DCC protein in the developing fetal mouse brain hippocampus compared with controls. Changes in the expression of cell migration cues during development could account for some of the lifelong consequences of maternal dietary choline availability for cognitive and memory processes.

Albright, Craig D.; Mar, Mei-Heng; Craciunescu, Corneliu N.; Song, Jiannan; Zeisel, Steven H.

2006-01-01

357

Oppositional Children Differ from Healthy Children in Frontal Brain Activation  

Microsoft Academic Search

An atypical EEG pattern of frontal brain activation, which has been found in children and adults with emotional disorders, also is hypothesized to be present in disruptive behavior disorders. One hundred nineteen children (4\\u000a

Lioba Baving; Manfred Laucht; Martin H. Schmidt

2000-01-01

358

New Method for the Study of Spontaneous Brain Activity.  

National Technical Information Service (NTIS)

A new method has been developed to characterize the sources of spontaneous brain activity measured magnetically while avoiding any specific model for the neural generators. In an application of the technique, individual spindles of the alpha rhythm monito...

R. J. Ilmoniemi S. J. Williamson W. E. Hostetler

1988-01-01

359

Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and brain of mice following oocyte in vitro maturation but postnatal brain development and cognitive function are normal.  

PubMed

Despite the efforts to recapitulate the follicle environment, oocytes from in vitro maturation (IVM) have poorer developmental potential than those matured in vivo and the effects on the resultant offspring are of concern. The aim of this study was to determine altered gene expression in oocytes following IVM and to evaluate the expression of the arginine rich, mutated in early stage of tumors gene (Armet) and mitochondrial ribosomal protein L51 (Mrpl51) in embryos and brains of fetal/postnatal mice and the brain development of IVM offspring. An IVM mouse model was established while oocytes matured in vivo were used as the controls. Suppressive subtractive hybridization (SSH) and RT-PCR/western blot were used to analyze the differential expression of genes/proteins between IVM and the control group. HE staining and water maze were used to assess the histological changes in brain tissue and cognition of the offspring. The rates of fertilization, cleavage, and live birth were significantly decreased in IVM group. Thirteen genes were upregulated in IVM oocytes compared with the control, including Armet and Mrpl51. The higher level of Armet in IVM oocytes was retained in brain of newborn mice, which could be related to the upregulation of activating transcription factor 6 (Atf6) and X-box binding protein 1 (Xbp1), while Mrpl51 was expressed normally in brain of postnatal mice. No significant differences were detected in brain weight, neuronal counts, and the cognition in the offspring between the two groups. The present results suggested that IVM could affect the pregnancy outcome and the Armet and Mrpl51 gene/protein expression. The change in Armet expression lasted while the change of Mrpl51 disappeared after birth. However, the brain development of the offspring seemed to be unaffected by IVM. PMID:21730110

Wang, Ning; Wang, Liya; Le, Fang; Zhan, Qitao; Zheng, Yingming; Ding, Guolian; Chen, Xijing; Sheng, Jianzhong; Dong, Minyue; Huang, Hefeng; Jin, Fan

2011-07-05

360

Aluminium induced structural, metabolic alterations and protective effects of desferrioxamine in the brain tissue of mice: An FTIR study  

NASA Astrophysics Data System (ADS)

In this study, we intended to made a new approach to evaluate aluminium induced metabolic changes in mice brain tissue using Fourier transform infrared spectroscopy. Results demonstrate that FTIR can successfully indicate the molecular changes that occur in all groups. The overall findings demonstrate the alterations on the major biochemical constituents, such as lipids, proteins and nucleic acids of the brain tissues of mice. The significant decrease in the area value of amide A peak and Olefinicdbnd CH stretching band suggests an alteration in the protein profile and lipid levels due to aluminium exposure, respectively. The significant shift in the amide I and amide II protein peaks may indicate the progression of aluminium induced Alzheimer's disease. Further the administration of DFO significantly improved the level of protein and brought back the amide I and II peaks nearer to the control value. Histopathological results also revealed impairment of Aluminium induced alterations in brain tissue. The results of the FTIR study were found to be in agreement with biochemical studies.

Sivakumar, S.; Sivasubramanian, J.; Raja, B.

2012-12-01

361

Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome.  

PubMed

Mitochondrial metabolism, respiration, and ATP production necessitate ion transport across the inner mitochondrial membrane. Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1), one of the genes deleted in Wolf-Hirschhorn syndrome, encodes a putative mitochondrial Ca(2+)/H(+) antiporter. Cellular Letm1 knockdown reduced Ca(2+)mito uptake, H(+)mito extrusion and impaired mitochondrial ATP generation capacity. Homozygous deletion of Letm1 in mice resulted in embryonic lethality before day 6.5 of embryogenesis and ~50% of the heterozygotes died before day 13.5 of embryogenesis. The surviving heterozygous mice exhibited altered glucose metabolism, impaired control of brain ATP levels, and increased seizure activity. We conclude that loss of Letm1 contributes to the pathology of Wolf-Hirschhorn syndrome in humans and may contribute to seizure phenotypes by reducing glucose oxidation and other specific metabolic alterations. PMID:23716663

Jiang, Dawei; Zhao, Linlin; Clish, Clary B; Clapham, David E

2013-05-28

362

Regional brain activation during verbal declarative memory in metastatic breast cancer  

PubMed Central

Purpose To determine the neurofunctional basis of verbal memory dysfunction in women with metastatic breast cancer. This objective was based on previous research suggesting memory and other cognitive deficits in this population. We attempted to determine if verbal memory impairments were related to the most commonly studied disease parameters including adjuvant chemotherapy and chronic stress-related disruption of limbic system structures. Experimental Design We utilized functional magnetic resonance imaging (fMRI) to test our hypothesis that women with breast cancer would demonstrate significantly lower brain activation during a verbal declarative memory tasks compared to age and education-matched healthy female controls. We also assessed several stress-related variables including diurnal cortisol levels to test our hypothesis that women with breast cancer would demonstrate higher stress and this would contribute to brain activation deficits during memory tasks. Results Women with breast cancer had significantly lower prefrontal cortex activation during the memory encoding condition compared to controls. However, the breast cancer group demonstrated significantly greater activation than controls during the recall condition in multiple, diffuse brain regions. There were no significant differences between the groups in stress-related variables. Women who were treated with CMF chemotherapy demonstrated lower prefrontal cortex activation during memory encoding. Conclusions These results suggest that women with metastatic breast cancer may be at risk for verbal memory impairments as a result of altered functional brain activation profiles. These findings may be associated with chemotherapy type and/or other aspects of the breast cancer disease process.

Kesler, Shelli R.; Bennett, F. Chris; Mahaffey, Misty L.; Spiegel, David

2010-01-01

363

Resting-State Brain Activity in Adult Males Who Stutter  

Microsoft Academic Search

Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with

Yun Xuan; Chun Meng; Yanhui Yang; Chaozhe Zhu; Liang Wang; Qian Yan; Chunlan Lin; Chunshui Yu

2012-01-01

364

Oxidative stress increases blood-brain barrier permeability and induces alterations in occludin during hypoxia-reoxygenation.  

PubMed

The blood-brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O(2) for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from the TJ. Furthermore, subcellular fractionation of cerebral microvessels reveals alterations in occludin oligomeric assemblies in TJ associated with plasma membrane lipid rafts. Our data suggest that pharmacological inhibition of disease states with an HR component may help preserve BBB functional integrity. PMID:20234382

Lochhead, Jeffrey J; McCaffrey, Gwen; Quigley, Colleen E; Finch, Jessica; DeMarco, Kristin M; Nametz, Nicole; Davis, Thomas P

2010-03-17

365

Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning.  

PubMed

Previous studies on mice with a disruption of the gene encoding acid-sensing ion channel 1a (ASIC1a) suggest that ASIC1a is required for normal fear behavior. To investigate the effects of altering the subunit composition of brain ASICs on behavior, we developed transgenic mice expressing ASIC3 via the pan-neuronal synapsin I promoter. These mice express ASIC3 in the brain, where the endogenous ASIC3 protein is not detected. We found that in ASIC3 transgenic mice, ASIC3 co-immunoprecipitated with the endogenous ASIC1a protein and distributed in the same subcellular brain fractions as ASIC1a. In addition, ASIC3 significantly increased the rate of desensitization of acid-evoked currents in cultured cortical neurons. Importantly, ASIC3 reduced Pavlovian fear conditioning to both context and auditory cues. These observations suggest that ASIC3 can heteromultimerize with ASIC1a in the brain and alter the biophysical properties of the endogenous channel complex. Moreover, these data suggest that ASIC subunit composition and channel desensitization may be critical determinants for ASIC-dependent behavior. PMID:21324060

Vralsted, V C; Price, M P; Du, J; Schnizler, M; Wunsch, A M; Ziemann, A E; Welsh, M J; Wemmie, J A

2011-03-07

366

Acute Stress Differentially Affects Aromatase Activity in Specific Brain Nuclei of Adult Male and Female Quail  

PubMed Central

The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress-induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15 min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction.

Cornil, Charlotte A.; Balthazart, Jacques

2011-01-01

367

Regional Brain Activation With Advertising Images  

Microsoft Academic Search

Preferences for purchasing goods and services may be shaped by many factors, including advertisements presenting logical, persuasive information or those using images or text that may modify behavior without requiring conscious recognition of a message. We tested the hypothesis that these two types of messages (logical persuasion [LP] vs. nonrational influence [NI]) might affect brain function differently in a pilot

Ian A. Cook; Clay Warren; Sarah K. Pajot; David Schairer; Andrew F. Leuchter

2011-01-01

368

GABAergic activities enhance macrophage inflammatory protein-1? release from microglia (brain macrophages) in postnatal mouse brain  

PubMed Central

Microglial cells (brain macrophages) invade the brain during embryonic and early postnatal development, migrate preferentially along fibre tracts to their final position and transform from an amoeboid to a ramified morphology. Signals by which the invading microglia communicate with other brain cells are largely unknown. Here, we studied amoeboid microglia in postnatal corpus callosum obtained from 6- to 8-day-old mice. These cells accumulated on the surface of acute brain slices. Whole-cell patch-clamp recordings revealed that the specific GABAA receptor agonist muscimol triggered a transient increase in conductance typical for inward rectifying potassium channels in microglia. This current increase was not mediated by microglial GABAA receptors since microglial cells removed from the slice surface no longer reacted and cultured microglia only responded when a brain slice was placed in their close vicinity. Muscimol triggered a transient increase in extracellular potassium concentration ([K+]o) in brain slices and an experimental elevation of [K+]o mimicked the muscimol response in microglial cells. Moreover, in adult brain slices, muscimol led only to a minute increase in [K+]o and microglial cells failed to respond to muscimol. In turn, an increase in [K+]o stimulated the release of chemokine macrophage inflammatory protein-1? (MIP1-?) from brain slices and from cultures of microglia but not astrocytes. Our observations indicate that invading microglia in early postnatal development sense GABAergic activities indirectly via sensing changes in [K+]o which results in an increase in MIP1-? release.

Cheung, Giselle; Kann, Oliver; Kohsaka, Shinichi; Faerber, Katrin; Kettenmann, Helmut

2009-01-01

369

Hexose monophosphate pathway activity in normal and hypoxic rat brain.  

PubMed

Experiments were undertaken to define the role of the alternative route of glucose metabolism in the hexose monophosphate pathway (HMP) during energy balanced, mild brain hypoxia. In similar hypoxic model in spite of the lack of the deficit of high energy compounds, the significant acceleration of glycolysis and inhibition of macromolecular syntheses (lipid, proteins, and nucleic acids) were previously observed. The HMP activity, although directly coupled to intracellular synthetic processes, has not been defined and little is known about the mechanisms of its regulation under brain hypoxia. HMP activity was examined in the rat brain in vivo by estimation of the increment of 6-phosphogluconate concentration after inhibition of its oxidation as achieved by injection of 6-aminonicotinamide. The activity of this alternative route of glucose metabolism was estimated to be 0.4 mmol/h/kg w.w. in the brain cortex and 0.7 mmol/h/kg w.w. in the brain stem. During 2 h of mild hypoxia (7% O2 in N2) the HMP activity dropped to 30% of control level, whereas during first hour of reoxygenation increased to 200% of control. Increased activity of HMP in posthypoxic brain during reoxygenation also was observed in vitro by measuring the rate of [1-14C]- and [6-14C]glucose conversion to 14CO2 in cerebral cortical slices. The possible mechanism of the rapid changes in the activity of HMP induced by hypoxia is discussed. The results suggest that the brain glucose metabolism under mild hypoxia is reoriented toward energy producing pathway (glycolysis) partially at the expense of HMP. The mechanism of this regulation seems not to be directly triggered by energy deficit. Activity of HMP in the brain is in accord with the intracellular synthetic processes and their demands on the metabolites produced by this pathway. Relying upon that, the posthypoxic stimulation of HMP would indicate the metabolic recovery during reoxygenation. PMID:2839885

Doma?ska-Janik, K

1988-04-01

370

Anatomical Atlas-Guided Diffuse Optical Tomography of Brain Activation  

PubMed Central

We describe a neuro imaging protocol that utilizes an anatomical atlas of the human head to guide Diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of Diffuse optical tomography images of brain activation.

Custo, Anna; Boas, David A.; Tsuzuki, Daisuke; Dan, Ippeita; Mesquita, Rickson; Fischl, Bruce; Grimson, W. Eric L.; Wells, Williams

2009-01-01

371

Anatomical atlas-guided diffuse optical tomography of brain activation.  

PubMed

We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median-nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of diffuse optical tomography images of brain activation. PMID:19643185

Custo, Anna; Boas, David A; Tsuzuki, Daisuke; Dan, Ippeita; Mesquita, Rickson; Fischl, Bruce; Grimson, W Eric L; Wells, Williams

2009-07-28

372

Activity of fish brain due to an alternation of gravity  

NASA Astrophysics Data System (ADS)

Fish serve as a good animal model for studying gravi-perception mechanism. Because they live in water, it is possible to see more natural effects of the gravity, with reduced influence on supporting tissue. Here, we investigated the effects of the gravity change on the brain of Medaka fish (Oryzias latipes ). Medaka fish kept at 1G were exposed to 2G, using a large centrifuge. Following the stimulation, we isolated mRNA from the Medaka brain, and studied the time-course and levels of their appearance. The gene expression pattern suggested the activation of the Medaka brain due to the hypergravity. Furthermore, we observed the areas in fish brain that are activated by hypergravity with an immunohistochemical method. Detailed pictures of the neural activity of Medaka fish due to a gravity shift are reported.

Shimomura, S.; Ijiri, K.

373

Aberrant temporal and spatial brain activity during rest in patients with chronic pain  

PubMed Central

In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system.

Malinen, Sanna; Vartiainen, Nuutti; Hlushchuk, Yevhen; Koskinen, Miika; Ramkumar, Pavan; Forss, Nina; Kalso, Eija; Hari, Riitta

2010-01-01

374

Early Risk, Attention, and Brain Activation in Adolescents Born Preterm  

ERIC Educational Resources Information Center

The relations among early cumulative medical risk, cumulative environmental risk, attentional control, and brain activation were assessed in 15-16-year-old adolescents who were born preterm. Functional magnetic resonance imaging found frontal, temporal, and parietal cortex activation during an attention task with greater activation of the left…

Carmody, Dennis P.; Bendersky, Margaret; Dunn, Stanley M.; DeMarco, J. Kevin; Hegyi, Thomas; Hiatt, Mark; Lewis, Michael

2006-01-01

375

Early Risk, Attention, and Brain Activation in Adolescents Born Preterm  

ERIC Educational Resources Information Center

|The relations among early cumulative medical risk, cumulative environmental risk, attentional control, and brain activation were assessed in 15-16-year-old adolescents who were born preterm. Functional magnetic resonance imaging found frontal, temporal, and parietal cortex activation during an attention task with greater activation of the left…

Carmody, Dennis P.; Bendersky, Margaret; Dunn, Stanley M.; DeMarco, J. Kevin; Hegyi, Thomas; Hiatt, Mark; Lewis, Michael

2006-01-01

376

Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity  

PubMed Central

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory – as occurs in autism – should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth – indicating a reduced reliance on long-distance connections – for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects.

Lewis, John D.; Elman, Jeffrey L.

2009-01-01

377

[Brain metabolism alterations in patients with anorexia nervosa observed in 1H-MRS  

Microsoft Academic Search

The causes of metabolic brain changes in patients with anorexia nervosa are still not fully explained. The purpose of this study was to use the 1H-MRS method in investigating metabolic changes in the brain of patients with anorexia nervosa. We studied 10 patients for visible alternations in brain metabolism and compared the results to healthy controls. 1H-MRS was acquired by

P. Grzelak; W. Gajewicz; A. Wyszogrodzka-Kucharska; A. Rotkiewicz; L. Stefanczyk; B. M. Goraj; J. Rabe-Jablonska

2005-01-01

378

Adolescent alcohol exposure alters the central brain circuits known to regulate the stress response  

Microsoft Academic Search

Adolescent alcohol exposure (AAE) may exert long-term effects on the adult brain. Here, we tested the hypothesis that the brain regions affected include the rat hypothalamic-pituitary-adrenal (HPA) axis. Specifically, we examined the consequences of AAE [postnatal days (PND) 28–42] on the HPA axis-related brain circuitry of male rats challenged with an intragastric (ig) administration of alcohol in young adulthood (PND

C. D. Allen; C. L. Rivier; S. Y. Lee

2011-01-01

379

Regulation of Prolactin in Mice with Altered Hypothalamic Melanocortin Activity  

PubMed Central

This study used two mouse models with genetic manipulation of the melanocortin system to investigate prolactin regulation. Mice with overexpression of the melanocortin receptor (MC-R) agonist, ?-melanocyte-stimulating hormone (Tg-MSH) or deletion of the MC-R antagonist agouti-related protein (AgRP KO) were studied. Male Tg-MSH mice had lower blood prolactin levels at baseline (2.9±0.3 vs 4.7±0.7 ng/ml) and after restraint stress(68 ±6.5 vs 117±22 ng/ml) versus WT (p<0.05); however, pituitary prolactin content was not different. Blood prolactin was also decreased in male AgRP KO mice at baseline (4.2±0.5 vs 7.6±1.3 ng/ml) and after stress (60±4.5 vs 86.1±5.7 ng/ml) vs WT (p <0.001). Pituitary prolactin content was lower in male AgRP KO mice (4.3±0.3 vs 6.7±0.5 ?g/pituitary, p <0.001) versus WT. No differences in blood or pituitary prolactin levels were observed in female AgRP KO mice versus WT. Hypothalamic dopamine activity was assessed as the potential mechanism responsible for changes in prolactin levels. Hypothalamic tyrosine hydroxylase mRNA was measured in both genetic models versus WT mice and hypothalamic dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content were measured in male AgRP KO and WT mice but neither were significantly different. However, these results do not preclude changes in dopamine activity as dopamine turnover was not directly investigated. This is the first study to show that baseline and stress-induced prolactin release and pituitary prolactin content are reduced in mice with genetic alterations of the melanocortin system and suggests that changes in hypothalamic melanocortin activity may be reflected in measurements of serum prolactin levels.

Dutia, Roxanne; Kim, Andrea J.; Mosharov, Eugene; Savontaus, Eriika; Chua, Streamson C.; Wardlaw, Sharon L.

2012-01-01

380

A Battery-Powered Activity-Dependent Intracortical Microstimulation IC for Brain-Machine-Brain Interface  

Microsoft Academic Search

This paper describes an activity-dependent intracor- tical microstimulation (ICMS) system-on-chip (SoC) that converts extracellular neural spikes recorded from one brain region to electrical stimuli delivered to another brain region in real time in vivo. The 10.9-mm SoC incorporates two identical 4-channel modules, each comprising an analog recording front-end with total input noise voltage of 3.12 V and noise efficiency factor

Meysam Azin; David J. Guggenmos; Scott Barbay; Randolph J. Nudo; Pedram Mohseni

2011-01-01

381

Evidence of altered posteromedial cortical fMRI activity in subjects at risk for Alzheimer disease  

PubMed Central

The posteromedial cortices and other regions of the “default network” are particularly vulnerable to the pathology of Alzheimer disease (AD). In this study, we performed fMRI to investigate whether the presence of apolipoprotein E (APOE) ?4 allele and degree of memory impairment were associated with dysfunction of these brain regions. Seventy-five elderly subjects ranging from cognitively normal to mild AD, divided into ?4 carriers and non-carriers, underwent fMRI during a memory encoding task. Across all subjects, posteromedial and ventral anterior cingulate cortices (key components of the default network) as well as right middle and inferior prefrontal regions demonstrated reduced task-induced deactivation in the ?4 carriers relative to non-carriers. Even among cognitively normal subjects, ?4 carriers demonstrated reduced posteromedial deactivation compared to non-carriers, in the same regions which demonstrated failure of deactivation in AD patients. Greater failure of posteromedial deactivation was related to worse memory performance (delayed recall) across all subjects and within the range of cognitively normal subjects. In summary, the posteromedial cortical fMRI response pattern is modulated both by the presence of APOE ?4 and episodic memory capability. Altered fMRI activity of the posteromedial areas of the brain default network may be an early indicator of risk for AD.

Pihlajamaki, Maija; O'Keefe, Kelly; Bertram, Lars; Tanzi, Rudolph E.; Dickerson, Bradford C.; Blacker, Deborah; Albert, Marilyn S.; Sperling, Reisa A.

2009-01-01

382

Mild blast events alter anxiety, memory, and neural activity patterns in the anterior cingulate cortex.  

PubMed

There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

Xie, Kun; Kuang, Hui; Tsien, Joe Z

2013-05-31

383

Mild Blast Events Alter Anxiety, Memory, and Neural Activity Patterns in the Anterior Cingulate Cortex  

PubMed Central

There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder.

Xie, Kun; Kuang, Hui; Tsien, Joe Z.

2013-01-01

384

[Rat brain nuclease activity during learning with emotionally different reinforcement].  

PubMed

Acid and alkaline activity of nucleases of the rats trained with emotional positive or negative reinforcement was estimated in the neocortex, hippocampus, midbrain, and in caudal portions of the brain-stem, using native and denaturated DNA as a substrate. The results showed the total increase in nuclease activity during learning. Nevertheless the dynamics of enzyme activation was different depending on the emotional state of rats during learning. The most active enzyme was found in the caudal portion of the brain-stem. PMID:37128

Tret'iak, T M; Semenova, T P; Smirnova, G N

1979-04-01

385

Alteration in glutathione homeostasis and oxidative stress during the sequelae of trimethyltin syndrome in rat brain.  

PubMed

Trimethyltin (TMT), a by-product of tin, is used in a wide variety of industrial and agricultural purposes which serves as a model neurotoxicant in hippocampal neurodegeneration, and this could, in turn, be exploited for various therapeutic compounds essential for hippocampal neurodegeneration. Therefore, the present investigation explores the sequential changes in behavior, oxidative burden, and apoptosis following TMT administration in rat hippocampus. Male SD rats weighing 250 g were given single dose of 8.5 mg/kg TMT (i.p.) that resulted in "TMT syndrome" which begins at the third post-TMT exposure and continued till 21 days posttreatment. This resulted in behavioral alteration (aggression and spontaneous seizures), cognitive impairment as assessed by plus maze, and passive avoidance resulting in short-term memory deficits. These behavioral alterations were associated with an increase in oxidative stress. The levels of malondialdehyde, reactive oxygen species, and protein carbonyl were significantly increased (p?activation at gene as well as protein level after TMT exposure on day 14, quoting an extent of changes. Therefore, it is proposed that behavioral deficits could be accounted by the impairment of endogenous glutathione homeostasis which resulted in death of neurons in the hippocampal region. PMID:23625697

Kaur, Sukhwinder; Nehru, Bimla

2013-04-28

386

Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa.  

PubMed

OBJECTIVE The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. METHOD The authors used structural MR imaging to study gray and white matter volumes in women with current restricting-type anorexia nervosa (N=19), women recovered from restricting-type anorexia nervosa (N=24), women with bulimia nervosa (N=19), and healthy comparison women (N=24). RESULTS All eating disorder groups exhibited increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manual tracing confirmed larger gyrus rectus volume, and volume predicted taste pleasantness ratings across all groups. Analyses also indicated other morphological differences between diagnostic categories. Antero-ventral insula gray matter volumes were increased on the right side in the anorexia nervosa and recovered anorexia nervosa groups and on the left side in the bulimia nervosa group relative to the healthy comparison group. Dorsal striatum volumes were reduced in the recovered anorexia nervosa and bulimia nervosa groups and predicted sensitivity to reward in all three eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas relative to the healthy comparison group. The results held when a range of covariates, such as age, depression, anxiety, and medications, were controlled for. CONCLUSION Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

Frank, Guido K; Shott, Megan E; Hagman, Jennifer O; Mittal, Vijay A

2013-10-01

387

Resting Cerebral Blood Flow Alterations in Chronic Traumatic Brain Injury: An Arterial Spin Labeling Perfusion fMRI Study  

PubMed Central

Abstract Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI.

Whyte, John; Patel, Sunil; Avants, Brian; Europa, Eduardo; Wang, Jiongjiong; Slattery, John; Gee, James C.; Coslett, H. Branch; Detre, John A.

2010-01-01

388

Light interference as a possible stressor altering HSP70 and its gene expression levels in brain and hepatic tissues of golden spiny mice.  

PubMed

Light at night and light interference (LI) disrupt the natural light:dark cycle, causing alterations at physiological and molecular levels, partly by suppressing melatonin (MLT) secretion at night. Heat shock proteins (HSPs) can be activated in response to environmental changes. We assessed changes in gene expression and protein level of HSP70 in brain and hepatic tissues of golden spiny mice (Acomys russatus) acclimated to LI for two (SLI), seven (MLI) and 21 nights (LLI). The effect of MLT treatment on LI-mice was also assessed. HSP70 levels increased in brain and hepatic tissues after SLI, whereas after MLI and LLI, HSP70 decreased to control levels. Changes in HSP70 levels as a response to MLT occurred after SLI only in hepatic tissue. However, hsp70 expression following SLI increased in brain tissue, but not in hepatic tissue. MLT treatment and SLI caused a decrease in hsp70 levels in brain tissue and an increase in hsp70 in hepatic tissue. SLI acclimation elicited a stress response in A. russatus, as expressed by increased HSP70 levels and gene expression. Longer acclimation decreases protein and gene expression to their control levels. We conclude that for brain and hepatic tissues of A. russatus, LI is a short-term stressor. Our results also revealed that A. russatus can acclimate to LI, possibly because of its circadian system plasticity, which allows it to behave both as a nocturnal and as a diurnal rodent. To the best of our knowledge, this is the first study showing the effect of LI as a stressor at the cellular level, by activating HSP70. PMID:22933613

Ashkenazi, Lilach; Haim, Abraham

2012-08-29

389

Brain Distribution of Cediranib Is Limited by Active Efflux at the Blood-Brain Barrier  

PubMed Central

Cediranib is an orally active tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor family. Because of its potent antiangiogenic and antitumor activities, cediranib has been evaluated for therapy in glioma, a primary brain tumor. This study investigated the influence of two important efflux transporters at the blood-brain barrier, P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), on the delivery of cediranib to the central nervous system. In vitro studies indicated that cediranib is a dual substrate for both P-gp and Bcrp. It is noteworthy that in spite of the in vitro data the in vivo mouse disposition studies conclusively showed that P-gp was the dominant transporter restricting the brain distribution of cediranib. The brain-to-plasma partitioning (AUCbrain/AUCplasma, where AUC is area under the curve) and the steady-state brain-to-plasma concentration ratio of cediranib were approximately 20-fold higher in Mdr1a/b(?/?) and Mdr1a/b(?/?)Bcrp1(?/?) mice compared with wild-type and Bcrp1(?/?) mice. Moreover, there was no significant difference in brain distribution of cediranib between wild-type and Bcrp1(?/?) mice and between Mdr1a/b(?/?) and Mdr1a/b(?/?)Bcrp1(?/?) mice. These results show that, unlike other tyrosine kinase inhibitors that are dual substrates for P-gp and Bcrp, Bcrp does not restrict the distribution of cediranib across the blood-brain barrier. We also show that inhibition of P-gp using specific or nonspecific inhibitors resulted in significantly enhanced delivery of cediranib to the brain. Concurrent administration of cediranib with chemical modulators of efflux transporters can be used as a strategy to enhance delivery and thus efficacy of cediranib in the brain. These findings are clinically relevant to the efficacy of cediranib chemotherapy in glioma.

Wang, Tianli; Agarwal, Sagar

2012-01-01

390

Alteration of the expression of pesticide-metabolizing enzymes in pregnant mice: potential role in the increased vulnerability of the developing brain.  

PubMed

Studies on therapeutic drug disposition in humans have shown significant alterations as the result of pregnancy. However, it is not known whether pesticide metabolic capacity changes throughout pregnancy, which could affect exposure of the developing brain. We sought to determine the effect of pregnancy on the expression of hepatic enzymes involved in the metabolism of pesticides. Livers were collected from virgin and pregnant C57BL/6 mice at gestational days (GD)7, GD11, GD14, GD17, and postpartum days (PD)1, PD15, and PD30. Relative mRNA expression of several enzymes involved in the metabolism of pesticides, including hepatic cytochromes (Cyp) P450s, carboxylesterases (Ces), and paraoxonase 1 (Pon1), were assessed in mice during gestation and the postpartum period. Compared with virgin mice, alterations in the expression occurred at multiple time points, with the largest changes observed on GD14. At this time point, the expression of most of the Cyps involved in pesticide metabolism in the liver (Cyp1a2, Cyp2d22, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp3a11) were downregulated by 30% or more. Expression of various Ces isoforms and Pon1 were also decreased along with Pon1 activity. These data demonstrate significant alterations in the expression of key enzymes that detoxify pesticides during pregnancy, which could alter exposure of developing animals to these chemicals. PMID:23223497

Fortin, Marie C; Aleksunes, Lauren M; Richardson, Jason R

2012-12-04

391

Altered Serotonin 2A Receptor Activity in Women Who Have Recovered From Bulimia Nervosa  

Microsoft Academic Search

Objective: The authors' goal was to confirm that brain seroto- nin (5-HT) alterations are present in patients who have recov- ered from bulimia nervosa. Positron emission tomography im- aging with (18F)altanserin was used to characterize binding of the 5-HT2A receptor, which might contribute to altered feeding, mood, or impulse control. Method: Nine women who had recovered from bulimia ner- vosa

Walter H. Kaye; Guido K. Frank; Carolyn C. Meltzer; Julie C. Price; Claire W. McConaha; Penelope J. Crossan; B. S. Kelly; L. Klump

2001-01-01

392

Pacing and awareness: brain regulation of physical activity.  

PubMed

The aim of this current opinion article is to provide a contemporary perspective on the role of brain regulatory control of paced performances in response to exercise challenges. There has been considerable recent conjecture as to the role of the brain during exercise, and it is now broadly accepted that fatigue does not occur without brain involvement and that all voluntary activity is likely to be paced at some level by the brain according to individualised priorities and knowledge of personal capabilities. This article examines the role of pacing in managing and distributing effort to successfully accomplish physical tasks, while extending existing theories on the role of the brain as a central controller of performance. The opinion proposed in this article is that a central regulator operates to control exercise performance but achieves this without the requirement of an intelligent central governor located in the subconscious brain. It seems likely that brain regulation operates at different levels of awareness, such that minor homeostatic challenges are addressed automatically without conscious awareness, while larger metabolic disturbances attract conscious awareness and evoke a behavioural response. This supports the view that the brain regulates exercise performance but that the interpretation of the mechanisms underlying this effect have not yet been fully elucidated. PMID:23990402

Edwards, A M; Polman, R C J

2013-11-01

393

PERINATAL EXPOSURE TO POLYCHLORINATED BIPHENYLS AROCLOR 1016 OR 1254 DID NOT ALTER BRAIN CATECHOLAMINES NOR DELAYED ALTERNATION PERFORMANCE IN LONG EVANS RATS  

EPA Science Inventory

Several reports have indicated that polychlorinated biphenyls (PCB) altered development of biogenic amine systems in the brain, impaired behavioral performances and disrupted maturation of the thyroid axis. The current study examines whether these developmental effects of PCB ar...

394

Chronic dietary mercury exposure causes oxidative stress, brain lesions, and altered behaviour in Atlantic salmon (Salmo salar) parr.  

PubMed

Atlantic salmon (Salmo salar L.) parr were fed for 4 months on fish meal based diets supplemented with mercuric chloride (0, 10, or 100 mg Hg kg(-1) DW) or methylmercury chloride (0, 5, or 10 mg Hg kg(-1) DW) to assess the effects of inorganic (Hg) and organic dietary mercury on brain lipid peroxidation and neurotoxicity. Lipid peroxidative products, endogenous anti oxidant enzymes, brain histopathology, and overall behaviour were measured. Methylmercury accumulated significantly in the brain of fish fed 5 or 10 mg kg(-1) by the end of the experiment, and inorganic mercury accumulated significantly in the brain only at 100 mg kg(-1) exposure levels. No mortality or growth reduction was observed in any of the exposure groups. Fish fed 5 mg kg(-1) methylmercury had a significant increase (2-fold) in the antioxidant enzyme super oxide dismutase (SOD) in the brain. At dietary levels of 10 mg kg(-1) methylmercury, a significant increase (7-fold) was observed in lipid peroxidative products (thiobarbituric acid reactive substances, TBARS) and a subsequently decrease (1.5-fold) in anti oxidant enzyme activity (SOD and glutathione peroxidase, GSH-Px). Fish fed 10 mg kg(-1) methylmercury also had pathological damage (vacoulation and necrosis), significantly reduced neural enzyme activity (5-fold reduced monoamine oxidase, MAO, activity), and reduced overall post-feeding activity behaviour. Pathological injury started in the brain stem and became more widespread in other areas of the brain at higher exposure levels. Fish fed 100 mg Hg kg(-1) inorganic mercury had significant reduced neural MAO activity and pathological changes (astrocyte proliferation) in the brain, however, neural SOD and GSH-Px enzyme activity, lipid peroxidative products (TBARS), and post feeding behaviour did not differ from controls. Compared with other organs, the brain is particular susceptible for dietary methylmercury induced lipid peroxidative stress at relative low exposure concentrations. Doses of dietary methylmercury in the range of 5 mg kg(-1) induces protective redox defences in the brain as seen from the induction of anti-oxidant enzyme SOD activity. However, above a threshold of 10 mg kg(-1) methylmercury these defences are overcome and lipid peroxidative injury (TBARS) as well as severe pathological damage and adverse behaviour become apparent. PMID:12932701

Berntssen, Marc H G; Aatland, Aase; Handy, Richard D

2003-10-01

395

Prenatal water deprivation alters brain angiotensin system and dipsogenic changes in the offspring  

Microsoft Academic Search

Objective: Central renin–angiotensin system (RAS) plays an important role in regulating body fluid balance. The present study determined the effect of maternal dehydration on brain expression levels of angiotensinogen, angiotensin II receptor subtypes, and dipsogenic responses in offspring. Methods: Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined.

Huiying Zhang; Yisun Fan; Fei Xia; Chunsong Geng; Caiping Mao; Shan Jiang; Rui He; Lubo Zhang; Zhice Xu

2011-01-01

396

Mitochondrial alterations in aging rat brain: effective role of (?)-epigallo catechin gallate  

Microsoft Academic Search

Aging is a multi-factorial process which involves deprivation in body's metabolism. Brain mitochondria are prone to oxidative damage owing to their high metabolic rate. The decline in antioxidant system during aging augments the neuronal damage to mitochondrial components like antioxidant system, Kreb's cycle enzymes and electron transport chain complexes. Since brain is an organ rich in fatty acids, lipid peroxidation

Ravichandran Srividhya; Kamelija Zarkovic; Marina Stroser; Georg Waeg; Neven Zarkovic; Periandavan Kalaiselvi

2009-01-01