Stress?restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

Harvey, Brian H.; Oosthuizen, Frasia; Brand, Linda; Wegener, Gregers; Stein, Dan J.

doi:10.1007/s00213-004-1836-4

Cited by 86 publications

(114 citation statements)

References 55 publications

(67 reference statements)

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“…Animal models support the notion that stress and trauma can alter GABA A -benzodiazepine binding density. 2,6,[36][37][38] In general, these animal models have shown decreased GABA A function and binding in the cerebral cortex and hippocampus. [3][4][5] This is the first benzodiazepine-GABA A receptor binding study in patients with PTSD that supports these preclinical data.…”

Section: Discussionmentioning

confidence: 99%

“…2 Exposure of rodents to inescapable foot shock, a model for stress-related depression characterized by deficits in learning and memory, resulted in decreased GABA A function and binding in the cerebral cortex and hippocampus. [3][4][5] Benzodiazepines, which modulate the GABA A receptor function, inhibit the startle response induced by predator stress.…”

Section: Introductionmentioning

confidence: 99%

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Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

et al. 2007

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c-Aminobutyric acid (GABA A ) receptors are thought to play an important role in modulating the central nervous system in response to stress. Animal data have shown alterations in the GABA A receptor complex by uncontrollable stressors. SPECT imaging with benzodiazepine ligands showed lower distribution volumes of the benzodiazepine-GABA A receptor in the prefrontal cortex of patients with post-traumatic stress disorder (PTSD) in one, but not in another study. The objective of the present study was to assess differences in the benzodiazepine-GABA A receptor complex in veterans with and without PTSD using [ 11 C]flumazenil and positron emission tomography (PET). Nine drug naive male Dutch veterans with deployment related PTSD and seven male Dutch veterans without PTSD were recruited, and matched for age, region and year of deployment. Each subject received a [ 11 C]flumazenil PET scan and a structural magnetic resonance imaging scan. Dynamic 3D PET scans with a total duration of 60 min were acquired, and binding in template based and manually defined regions of interest (ROI) was quantified using validated plasma input and reference tissue models. In addition, parametric binding potential images were compared on a voxel-by-voxel basis using statistical parametric mapping (SPM2). ROI analyses using both template based and manual ROIs showed significantly reduced [ 11 C]flumazenil binding in PTSD subjects throughout the cortex, hippocampus and thalamus. SPM analysis confirmed these results. The observed global reduction of [ 11 C]flumazenil binding in patients with PTSD provides circumstantial evidence for the role of the benzodiazepine-GABA A receptor in the pathophysiology of PTSD and is consistent with previous animal research and clinical psychopharmacological studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

et al. 2007

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“…Stress, a risk factor for developing PTSD, evokes a sustained increase in nitric oxide synthase (NOS) activity that can generate excessive amounts of nitric oxide (Harvey et al, 2004). Oxidation of nitric oxide produces peroxynitrite that is very toxic to nerve cells (Ebadi et al, 2001).…”

Section: Oxidative Stress In Ptsdmentioning

confidence: 99%

“…This is logical because glutamate at high doses is known to be neurotoxic. Glutamate and nitric oxide (NO) released during stress play a central role in maintaining anxiety disorders (Joca et al, 2007;Harvey et al, 2004). Stress activates glutamate-NMDA receptors and decreases BDNF, and excessive amounts of glutamate can cause death of cholinergic neurons.…”

Section: 3mentioning

confidence: 99%

“…Stress activates glutamate-NMDA receptors and decreases BDNF, and excessive amounts of glutamate can cause death of cholinergic neurons. This may account for the cognitive dysfunction associated with PTSD (Harvey et al, 2004;Nair and Singh Ajit, 2008). The antagonists of NMDA receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPA receptors) are useful in reducing anxiety-related disorders (Riaza Bermudo-Soriano et al, 2012;Walker and Davis, 2002).…”

Section: 3mentioning

confidence: 99%

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Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Prasad¹,

Bondy

2015

Brain Research

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AnxietyPsychological damage a b s t r a c t Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

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Reduced Prefrontal Glutamate/Glutamine and γ-Aminobutyric Acid Levels in Major Depression Determined Using Proton Magnetic Resonance Spectroscopy

Hasler¹,

Veen²,

Tumonis³

et al. 2007

Arch Gen Psychiatry

768

502

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Context: Increasing evidence indicates that major depressive disorder (MDD) is associated with altered function of the major excitatory and inhibitory neurotransmitters glutamate and ␥-aminobutyric acid (GABA), respectively. A recently developed magnetic resonance spectroscopy method allows for reliable measurement of glutamate/glutamine (Glx) and GABA concentrations in prefrontal brain regions that have been implicated in the pathophysiologic mechanisms of MDD by studies using other neuroimaging and postmortem techniques.Objective: To measure Glx and GABA levels in 2 regions of the prefrontal brain tissue in unmedicated adults with MDD.Design: Cross-sectional study for association.Setting: Psychiatric outpatient clinic.Participants: Twenty unmedicated, depressed patients with MDD and 20 age-and sex-matched controls.Intervention: Participants underwent scanning using a 3-T whole-body scanner with a transmit-receive head coil, providing a homogeneous radiofrequency field and the capability of obtaining spectroscopic measurements in a dorsomedial/dorsal anterolateral prefrontal region of interest (ROI) and a ventromedial prefrontal ROI. Main Outcome Measures:Glx and GABA levels derived from magnetic resonance spectroscopy signals.Results: Depressed patients had reduced Glx levels in both ROIs. The GABA levels were reduced in the dorsomedial/dorsal anterolateral prefrontal ROI. Levels of GABA and Glx were positively correlated in both ROIs. Conclusions:For the first time, GABA and Glx concentrations were compared between unmedicated depressed adults and controls in prefrontal ROIs. The abnormal reductions in Glx and GABA concentrations found in the MDD sample were compatible with findings from postmortem histopathologic studies, indicating that glial cell density is reduced in the same areas in MDD.

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Stress?restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

Cited by 86 publications

References 55 publications

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Reduced Prefrontal Glutamate/Glutamine and γ-Aminobutyric Acid Levels in Major Depression Determined Using Proton Magnetic Resonance Spectroscopy

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