The aging human cochlear nucleus: Changes in the glial fibrillary acidic protein, intracellular calcium regulatory proteins, GABA neurotransmitter and cholinergic receptor

Publication date: March 2014 Source:Journal of Chemical Neuroanatomy, Volume 56 Author(s): Saroj Sharma , Tapas C. Nag , Alok Thakar , Daya N. Bhardwaj , Tara Sankar Roy The human auditory system is highly susceptible to environmental and metabolic insults which further affect the biochemical and physiological milieu of the cells that may contribute to progressive, hearing loss with aging. The cochlear nucleus (CN) is populated by morphologically diverse types of neurons with discrete physiological and neurochemical properties. Between the dorsal and the ventral cochlear nucleus (DCN and VCN), the VCN is further sub-divided into the rostral (rVCN) and caudal (cVCN) sub-divisions. Although, information is available on the age related neurochemical changes in the mammalian CN similar reports on human CN is still sparse. The morphometry and semiquantitative analysis of intensity of expression of glial fibrillary acidic protein (GFAP), calcium binding proteins (calbindin, calretinin and parvalbumin), gamma amino butyric acid (GABA) and nicotinic acetyl choline receptor (nAchR) beta 2 immunostaining were carried out in all three sub-divisions of the human CN from birth to 90 years. There was increased GFAP immunoreactivity in decades 2 and 3 in comparison to decade 1 in the CN. But no change was observed in rVCN from decade 4 onwards, whereas intense staining was also observed in decades 5 and 6 in cVCN and DCN. All three calcium binding proteins were highly expressed in early t...
Source: Journal of Chemical Neuroanatomy - Category: Neuroscience Source Type: research

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Publication date: Available online 27 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Yunus Akkoc, Devrim GozuacikAbstractAutophagy is a cellular stress response mechanism activation of which leads to degradation of cellular components, including proteins as well as damaged organelles in lysosomes. Defects in autophagy mechanisms were associated with several pathologies (e.g. cancer, neurodegenerative diseases, and rare genetic diseases). Therefore, autophagy regulation is under strict control. Transcriptional and post-translational mechanisms that control autophagy in cells and ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research
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Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
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Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
A single subanesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates this increase and ketamine’s behavioral actions has not been identified. To address this question, we used a combination of viral shRNA and conditional mutation to produce cell-specific knockdown or deletion of a key NMDAR subunit, GluN2B, impli...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Hematological malignancies have long been at the forefront of the development of novel immune-based treatment strategies. The earliest successful efforts originated from the extensive body of work in the field of allogeneic hematopoietic stem cell transplantation. These efforts laid the foundation for the recent exciting era of cancer immunotherapy, which includes immune checkpoint blockade, personal neoantigen vaccines, and adoptive T cell transfer. At the heart of the specificity of these novel strategies is the recognition of target antigens presented by malignant cells to T cells. Here, we review the advances in system...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects. Here we show development of tolerance in Morquio A mice via oral delivery of peptide or GALNS for 10 days prior to ERT. Our results show that using an immunodominant peptide (I10) or the complete GALNS enzyme to orally ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Cortical hyperexcitability and mislocalization of the RNA-binding protein TDP43 are highly conserved features in amyotrophic lateral sclerosis (ALS). Nevertheless, the relationship between these phenomena remains poorly defined. Here, we showed that hyperexcitability recapitulates TDP43 pathology by upregulating shortened TDP43 (sTDP43) splice isoforms. These truncated isoforms accumulated in the cytoplasm and formed insoluble inclusions that sequestered full-length TDP43 via preserved N-terminal interactions. Consistent with these findings, sTDP43 overexpression was toxic to mammalian neurons, suggesting neurodegeneration...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The human lipidome comprises over tens of thousands of distinct lipid species in addition to total cholesterol and the other conventional lipid traits that are routinely measurable in the peripheral circulation. Of the lipid species considered to exhibit bioactive functions, sphingolipids are a class of molecules that have shown relevance to human disease risk and cardiovascular outcomes in particular. In this issue of the JCI, Poss et al. conducted targeted lipidomics in a case-control study involving over 600 individuals and found a sphingolipid profile that predicted coronary artery disease status. In the context of eme...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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