Microanatomical Findings in Postmortem Brain Tissue from Subjects with Schizophrenia: Disturbances in Thalamocortical and Corticocortical Connectivity in Schizophrenia

2002 ◽  
pp. 151-171
Author(s):  
T. Hashimoto ◽  
D. A. Lewis
Keyword(s):  
Brain Tissue ◽  
Postmortem Brain ◽  
Postmortem Brain Tissue

scholarly journals Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Preeti Singh ◽  
Peter S. Hanson ◽  
Christopher M. Morris
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Neural Cells ◽  
Compensatory Mechanism ◽  
Postmortem Brain Tissue ◽  
Lysine Deacetylases ◽  
Neuronal Stress

Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along withα-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation ofα-synuclein aggregates but showed minimal colocalisation withα-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.

Cells in human postmortem brain tissue slices remain alive for several weeks in culture

2002 ◽  
Vol 16 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Ronald W. H. Verwer ◽  
Wim T. J. M. C. Hermens ◽  
Paul A. Dijkhuizen ◽  
Olivier Ter Brake ◽  
Robert E. Baker ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Postmortem Brain ◽  
Tissue Slices ◽  
Human Postmortem Brain ◽  
Postmortem Brain Tissue

scholarly journals Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain

2019 ◽  
Vol 11 (523) ◽  
pp. eaao6545 ◽  
Author(s):  
Jeanna M. Wheeler ◽  
Pamela McMillan ◽  
Timothy J. Strovas ◽  
Nicole F. Liachko ◽  
Alexandre Amlie-Wolf ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Brain Tissue ◽  
Rna Binding ◽  
Binding Protein ◽  
Disease Onset ◽  
Tail Length ◽  
Postmortem Brain ◽  
Mammalian Brain ◽  
Macromolecular Complex ◽  
Postmortem Brain Tissue

Brain lesions composed of pathological tau help to drive neurodegeneration in Alzheimer’s disease (AD) and related tauopathies. Here, we identified the mammalian suppressor of tauopathy 2 (MSUT2) gene as a modifier of susceptibility to tau toxicity in two mouse models of tauopathy. Transgenic PS19 mice overexpressing tau, a model of AD, and lacking the Msut2 gene exhibited decreased learning and memory deficits, reduced neurodegeneration, and reduced accumulation of pathological tau compared to PS19 tau transgenic mice expressing Msut2. Conversely, Msut2 overexpression in 4RTauTg2652 tau transgenic mice increased pathological tau deposition and promoted the neuroinflammatory response to pathological tau. MSUT2 is a poly(A) RNA binding protein that antagonizes the canonical nuclear poly(A) binding protein PABPN1. In individuals with AD, MSUT2 abundance in postmortem brain tissue predicted an earlier age of disease onset. Postmortem AD brain tissue samples with normal amounts of MSUT2 showed elevated neuroinflammation associated with tau pathology. We observed co-depletion of MSUT2 and PABPN1 in postmortem brain samples from a subset of AD cases with higher tau burden and increased neuronal loss. This suggested that MSUT2 and PABPN1 may act together in a macromolecular complex bound to poly(A) RNA. Although MSUT2 and PABPN1 had opposing effects on both tau aggregation and poly(A) RNA tail length, we found that increased poly(A) tail length did not ameliorate tauopathy, implicating other functions of the MSUT2/PABPN1 complex in tau proteostasis. Our findings implicate poly(A) RNA binding proteins both as modulators of pathological tau toxicity in AD and as potential molecular targets for interventions to slow neurodegeneration in tauopathies.

scholarly journals Premature neuronal differentiation in familial Alzheimer’s disease human stem cells in vitro and in postmortem brain tissue

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Charles Arber ◽  
Christopher E.J. Lovejoy ◽  
Nanet Willumsen ◽  
Argyro Alatza ◽  
Jackie M. Casey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Stem Cells ◽  
Neuronal Differentiation ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Human Stem Cells ◽  
Familial Alzheimer’S Disease ◽  
Postmortem Brain Tissue ◽  
Familial Alzheimer's Disease
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