scholarly journals Neurocognitive and neuroinflammatory correlates of PDYN and OPRK1 mRNA expression in the anterior cingulate in postmortem brain of HIV-infected subjects

2014 ◽  
Vol 11 (1) ◽  
pp. 5 ◽  
Author(s):  
Vadim Yuferov ◽  
Eduardo R Butelman ◽  
Ann Ho ◽  
Susan Morgello ◽  
Mary Kreek
Keyword(s):  
Mrna Expression ◽  
Anterior Cingulate ◽  
Postmortem Brain

scholarly journals Dysregulation of protein kinase C in adult depression and suicide: evidence from postmortem brain studies

2021 ◽  
Author(s):  
Ghanshyam N Pandey ◽  
Anuradha Sharma ◽  
Hooriyah S Rizavi ◽  
Xinguo Ren
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Mrna Expression ◽  
Postmortem Brain ◽  
Cortical Region ◽  
Cytosol Fraction ◽  
Kinase C ◽  
Pkc Isozymes

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region [Brodmann area 9 (BA9)] in 24 normal control (NC) subjects, 24 depressed suicide (DS) subjects and 12 depressed non-suicide (DNS) subjects. The levels of mRNA in the prefrontal cortex (PFC) were determined by qRT-PCR and the protein expression was determined by Western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ and PKCε and decreased protein expression either in the membrane or the cytosol fraction of PKC isozymes - PKCα, PKCβI, PKCβII and PKCδ in DS and DNS subjects compared with NC subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.

scholarly journals Dynamic landscape and genetic regulation of RNA editing in schizophrenia

2018 ◽  
Author(s):  
Michael S. Breen ◽  
Amanda Dobbyn ◽  
Qin Li ◽  
Panos Roussos ◽  
Gabriel E. Hoffman ◽  
...  
Keyword(s):  
Rna Editing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genetic Regulation ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Postmortem Brain ◽  
Sequence Motifs ◽  
Translational Initiation ◽  
Regulatory Variants

ABSTRACTRNA editing is vital for neurodevelopment and the maintenance of normal neuronal function. We surveyed the global landscape and genetic regulation of RNA editing across several hundred schizophrenia and control postmortem brain samples from the CommonMind Consortium covering two regions, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex. In schizophrenia, RNA editing sites encoding AMPA glutamate receptors and post-synaptic density genes were less edited, while more editing was detected in sites implicated in translational initiation. These sites replicate between brain regions, map to 3’UTRs, enrich for common sequence motifs and coincide for RNA binding proteins crucial for neurodevelopment. Importantly, these findings cross-validate in hundreds of non-overlapping DLPFC samples. Furthermore, ~30% of RNA editing sites associate with cis-regulatory variants (edQTLs). Fine-mapping edQTLs with schizophrenia GWAS loci revealed colocalization of 11 edQTLs with 6 GWAS loci. This supports a causal role of RNA editing in risk for schizophrenia. Our findings illustrate widespread altered RNA editing in schizophrenia and its genetic regulation, and shed light onto RNA editing-mediated mechanisms in schizophrenia neuropathology.

scholarly journals Thrombopoietin Contributes to Neuronal Damage in Experimental Bacterial Meningitis

2010 ◽  
Vol 79 (2) ◽  
pp. 928-936 ◽  
Author(s):  
Olaf Hoffmann ◽  
Olga Rung ◽  
Ae-Rie Im ◽  
Dorette Freyer ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Mrna Expression ◽  
Neuronal Damage ◽  
Postmortem Brain ◽  
Wild Type ◽  
Human Postmortem Brain ◽  
Raw264.7 Macrophages ◽  
Csf Pleocytosis ◽  
Hydrogen Peroxide Formation ◽  
The Brain

ABSTRACTThrombopoietin (Tpo), which primarily regulates megakaryopoiesis, and its receptor (c-Mpl) are expressed in the brain, where Tpo exhibits proapototic effects on neurons. In the present study, we investigated the implication ofTpoin experimental pneumococcal meningitis. Following intrathecal infection with the encapsulatedStreptococcus pneumoniaestrain D39, we observed upregulation ofTpomRNA expression at 12 h and 24 h in brain homogenates of wild-type C57BL/6 mice. c-MplmRNA expression was upregulated at 12 h and returned to baseline at 24 h. Compared to wild-type mice, mutants with homozygous Tpo receptor ablation (c-Mpl−/−) displayed reduced microglial activation and neuronal apoptosis in the dentate gyrus. Concentrations of bacteria in blood or cerebrospinal fluid (CSF), as well as CSF pleocytosis, were not significantly different between wild-type and c-Mpl−/−mice. In human postmortem brain, Tpo protein was colocalized to macrophages during encephalitis. In murine primary microglia and RAW264.7 macrophages, upregulation ofTpomRNA was induced by D39-conditioned medium but not by bacterial lipopeptide or by medium conditioned by pneumococcal mutants defective in hydrogen peroxide formation (ΔspxB) or pneumolysin (Δpln). We conclude that Tpo acts as a mediator of neuronal damage in bacterial meningitis.

BDNF-trkB signaling in late life cognitive decline and Alzheimer’s disease

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Hoau-Yan Wang ◽  
Andres Stucky ◽  
Chang-Gyu Hahn ◽  
Robert Wilson ◽  
David Bennett ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Signaling Pathway ◽  
Neurofibrillary Tangle ◽  
Anterior Cingulate ◽  
Postmortem Brain ◽  
Downstream Signaling ◽  
Postmortem Brain Tissue ◽  
Neurotrophin Signaling ◽  
Neurodegenerative Dementias ◽  
Stimulation Paradigm

AbstractExpression levels of BDNF and trkB, primary components of an important neurotrophin signaling pathway, have been reported to be abnormal in neurodegenerative dementias. Here, we used a novel postmortem brain tissue stimulation paradigm to examine BDNF-induced trkB signaling in participants of the Religious Orders Study, a large longitudinal clinicopathological study of aging and cognition. Thawed slices of anterior cingulate cortex were incubated in BDNF and changes in phosphorylated trkB and downstream signaling molecules ERK2 and Akt were measured, as well as the association of NMDA receptors with trkB. We found that stimulation with BDNF induced much greater activity of the BDNF-trkB signaling pathway in brain tissues of people with cognitive decline and AD, as evidenced by significantly more phosphorylation of trkB (pY-trkB), ERK2 (pY/pT-ERK2), Akt (pS-Akt), and greater BDNF-induced coupling of trKB with NMDAR2A/B. These findings were independent of PHFtau neurofibrillary tangle and amyloid-b plaque densities and other potentially confounding variables. Regression analyses with clinical features further characterized significant relationships between measures of BDNF-trkB activation and domains of cognition and emotional functioning. Increased BDNF-trkB signaling with cognitive decline could reflect a primary derangement of pathway functioning or a compensatory neuroplastic response to counteract neural injury associated with neurodegenerative processes.

scholarly journals Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism

2013 ◽  
Vol 4 (1) ◽  
pp. 6 ◽  
Author(s):  
Chie Shimmura ◽  
Katsuaki Suzuki ◽  
Yasuhide Iwata ◽  
Kenji J Tsuchiya ◽  
Koji Ohno ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Postmortem Brain

scholarly journals Cellular abnormalities in depression: evidence from postmortem brain tissue

2004 ◽  
Vol 6 (2) ◽  
pp. 185-197
Keyword(s):  
Brain Tissue ◽  
Basic Research ◽  
Brain Regions ◽  
Microscopic Level ◽  
Anterior Cingulate ◽  
Postmortem Brain ◽  
Cell Counting ◽  
The Past ◽  
Postmortem Brain Tissue

During the past two decades, in vivo neuroimaging studies have permitted significant insights into the general location of dysfunctional brain regions in depression. In parallel and often intersecting ways, neuroanatomical, pharmacological, and biochemical studies of postmortem brain tissue are permitting new insights into the pathophysiology of depression. In addition to long-recognized neurochemical abnormalities in depression, novel studies at the microscopic level support the contention that mood disorders are associated with abnormalities in cell morphology and distribution. In the past 6 years, cell-counting studies have identified changes in the density and size of both neurons and glia in a number of frontolimbic brain regions, including dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortex, and the amygdala and hippocampus. Convergence of cellular changes at the microscopic level with neuroimaging changes detected in vivo provides a compelling integration of clinical and basic research for disentangling the pathophysiology of depression. The ultimate integration of these two research approaches will occur with premortem longitudinal clinical studies on well-characterized patients linked to postmortem studies of the same subjects.

scholarly journals Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with neuropathic pain

2021 ◽  
Author(s):  
Stephanie Shiers ◽  
Hajira Elahi ◽  
Stephanie Hennen ◽  
Theodore J Price
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Mrna Expression ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Visceral Pain ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Mechanical Hypersensitivity

AbstractThe anterior cingulate cortex (ACC) is a critical region of the brain for the emotional and affective components of pain in rodents and humans. Hyperactivity in this region has been observed in neuropathic pain states in both patients and animal models and ablation of this region from cingulotomy, or inhibition with genetics or pharmacology can diminish pain and anxiety. Two adenylyl cyclases (AC), AC1 and AC8 play an important role in regulating nociception and anxiety-like behaviors through an action in the ACC, as genetic and pharmacological targeting of these enzymes reduces mechanical hypersensitivity and anxietylike behavior, respectively. However, the distribution of these ACs in the ACC has not been studied in the context of neuropathic pain. To address this gap in knowledge, we conducted RNAscope in situ hybridization to assess AC1 and AC8 mRNA distribution in mice with spared nerve injury (SNI). Given the key role of AC1 in nociception in neuropathic, inflammatory and visceral pain animal models, we hypothesized that AC1 would be upregulated in the ACC of mice following nerve injury. This hypothesis was also founded on data showing increased AC1 expression in the ACC of mice with zymosan-induced visceral inflammation. We found that AC1 and AC8 are widely expressed in many regions of the mouse brain including the hippocampus, ACC, medial prefrontal cortex and midbrain regions, but AC1 is more highly expressed. Contrary to our hypothesis, SNI causes an increase in AC8 mRNA expression in NMDAR-2B (Nr2b) positive neurons in the contralateral ACC but does not affect AC1 mRNA expression. Our findings show that changes in Adcy1 mRNA expression in the ACC are insufficient to explain the important role of this AC in mechanical hypersensitivity in mice following nerve injury and suggest a potential unappreciated role of AC8 in regulation of ACC synaptic changes after nerve injury.

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