Astrocytic changes with aging and Alzheimer's disease-type pathology in chimpanzees.
aging; Alzheimer's disease; astrocytes; cerebral cortex; chimpanzees; hippocampus; prefrontal cortex; RRID: AB2109645; RRID: AB223647; RRID: AB2313952; RRID: AB2314223; stereology
Astrocytes are the main homeostatic cell of the central nervous system. In addition, astrocytes mediate an inflammatory response when reactive to injury or disease known as astrogliosis. Astrogliosis is marked by an increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Some degree of astrogliosis is associated with normal aging and degenerative conditions such as Alzheimer's disease (AD) and other dementing illnesses in humans. The recent observation of pathological markers of AD (amyloid plaques and neurofibrillary tangles) in aged chimpanzee brains provided an opportunity to examine the relationships among aging, AD-type pathology, and astrocyte activation in our closest living relatives. Stereologic methods were used to quantify
Munger Emily L; Edler Melissa K; Hopkins William D; Ely John J; Erwin Joseph M; Perl Daniel P; Mufson Elliott J; Hof Patrick R; Sherwood Chet C; Raghanti Mary Ann
The Journal of comparative neurology
2018
2018-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/cne.24610" target="_blank" rel="noreferrer noopener">10.1002/cne.24610</a>
Astrocytic changes with aging and Alzheimer's disease-type pathology in chimpanzees
Aging; Alzheimer's disease; astrocytes; cerebral cortex; chimpanzees; hippocampus; prefrontal cortex; RRID: AB2109645; RRID: AB223647; RRID: AB2313952; RRID: AB2314223; stereology
Astrocytes are the main homeostatic cell of the central nervous system. In addition, astrocytes mediate an inflammatory response when reactive to injury or disease known as astrogliosis. Astrogliosis is marked by an increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Some degree of astrogliosis is associated with normal aging and degenerative conditions such as Alzheimer's disease (AD) and other dementing illnesses in humans. The recent observation of pathological markers of AD (amyloid plaques and neurofibrillary tangles) in aged chimpanzee brains provided an opportunity to examine the relationships among aging, AD-type pathology, and astrocyte activation in our closest living relatives. Stereologic methods were used to quantify GFAP-immunoreactive astrocyte density and soma volume in layers I, III, and V of the prefrontal and middle temporal cortex, as well as in hippocampal fields CA1 and CA3. We found that the patterns of astrocyte activation in the aged chimpanzee brain are distinct from humans. GFAP expression does not increase with age in chimpanzees, possibly indicative of lower oxidative stress loads. Similar to humans, chimpanzee layer I astrocytes in the prefrontal cortex are susceptible to AD-like changes. Both prefrontal cortex layer I and hippocampal astrocytes exhibit a high degree of astrogliosis that is positively correlated with accumulation of amyloid beta and tau proteins. However, unlike humans, chimpanzees do not display astrogliosis in other cortical layers. These results demonstrate a unique pattern of cortical aging in chimpanzees and suggest that inflammatory processes may differ between humans and chimpanzees in response to pathology.
Munger Emily L; Edler Melissa K; Hopkins William D; Ely John J; Erwin Joseph M; Perl Daniel P; Mufson Elliott J; Hof Patrick R; Sherwood Chet C; Raghanti Mary Ann
The Journal of Comparative Neurology
2019
2019-05
<a href="http://doi.org/10.1002/cne.24610" target="_blank" rel="noreferrer noopener">10.1002/cne.24610</a>
Repeated stressor exposure regionally enhances beta-adrenergic receptor-mediated brain IL-1 beta production
Anhedonia; antidepressant treatments; Chronic mild stress; chronic psychosocial stress; Cytokine; depression; depressive-like behavior; hippocampal neurogenesis; Immunology; inflammatory cytokines; ligand-binding; messenger-rna; Neurosciences & Neurology; Norepinephrine; paraventricular nucleus; prefrontal cortex; Psychiatry; rat; rat-brain; Receptor binding; Sensitization
It has been proposed that increased brain cytokines during repeated stressor exposure can contribute to neuropathological changes that lead to the onset of depression. Previous studies demonstrate that norepinephrine acting via beta-adrenergic receptors (beta-ARs) mediate brain IL-1 production during acute stressor exposure. The aim of the current studies was to examine how the regulation of brain cytokines by adrenergic signaling might change following repeated stressor exposure. Fischer rats were exposed to four days of chronic mild stress and 24 h after the last stressors beta-AR expression, norepinephrine turnover, and beta-AR-mediated induction of brain IL-1 were measured in limbic areas (e.g. hypothalamus, hippocampus, amygdala, and prefrontal cortex) and brainstem. Repeated stressor exposure resulted in decreases in beta-AR expression (B-max) measured by saturation binding curves in many limbic brain areas, while an increase was observed in the brainstem. This coincided with significant increases in norepinephrine turnover in the prefrontal cortex, hypothalamus, and amygdala, a significant increase in norepinephrine turnover was not observed in the hippocampus or brainstem. Stress increased overall IL-1 production in the amygdala (both basal and stimulated). While stress did not affect basal IL-1 levels in any other brain area, central administration of isoproterenol (a beta-AR agonist) augmented IL-1 production in the hypothalamus of stressed animals. These data indicate that repeated stressor exposure results in brain area specific enhancements in beta-AR-mediated IL-1 production and extends current knowledge of stress-induced enhancement of brain cytokine beyond sensitized response to immunological stimuli. (C) 2012 Elsevier Inc. All rights reserved.
Porterfield V M; Gabella K M; Simmons M A; Johnson J D
Brain Behavior and Immunity
2012
2012-11
Journal Article
<a href="http://doi.org/10.1016/j.bbi.2012.08.001" target="_blank" rel="noreferrer noopener">10.1016/j.bbi.2012.08.001</a>
Brain Macrostructural And Microstructural Abnormalities In Cocaine Dependence
abstinent; abuse; addiction; alcohol; brain; chronic cerebral hypoperfusion; cocaine; dependence; diffusion tensor imaging (DTI); drug-abuse; gerbil brain; magnetic resonance imaging (MRI); prefrontal cortex; Psychiatry; schizophrenia; Substance Abuse; users; white-matter integrity
Rationale: Two previous studies have utilized diffusion tensor imaging (DTI) to examine microstructural integrity in cocaine abuse and found 41 evidence of brain abnormalities in white matter. Objective: Using anatomical magnetic resonance imaging (MRI), DTI, and clinical evaluation, the macrostructural and microstructural correlates of cocaine abuse were investigated. Methods: Twenty-one men and women (mean age 42.5 and mean 18.9 years of cocaine use) and 21 age/gender-matched controls were included. Fractional anisotropy (FA) was measured in frontal white matter ROIs. Gray and white matter volumes in superior and inferior frontal regions were compared. Results: DTI data revealed that cocaine users had lower FA than controls, specifically in inferior frontal white matter. FA differences were not seen in other areas. Significant volumetric differences were not seen, but both gray and white matter inferior frontal volumes trended toward smaller in the cocaine group. The data suggested that duration of use was associated with decreased gray and white matter volumes. FA and gray matter volume were correlated in cocaine users. Conclusions: Both macrostructural and microstructural abnormalities were seen in a group of cocaine abusers. Length of cocaine use was associated with severity of the brain abnormalities. Future studies of white matter tissue integrity are warranted including examination of the relationship between DTI measures and traditional volumetric measures. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
Lim K O; Wozniak J R; Mueller B A; Franc D T; Specker S M; Rodriguez C P; Silverman A B; Rotrosen J P
Drug and Alcohol Dependence
2008
2008-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.drugalcdep.2007.07.019" target="_blank" rel="noreferrer noopener">10.1016/j.drugalcdep.2007.07.019</a>