Browsing by Author "Bhuvnesh Kumar"

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Correction to: Epigenetic Regulation of SNAP25 Prevents Progressive Glutamate Excitotoxicty in Hypoxic CA3 Neurons (Molecular Neurobiology, (2017), 54, 8, (6133-6147), 10.1007/s12035-016-0156-0)
(Springer, 2020) Suryanarayan Biswal; Debashree Das; Kalpana Barhwal; Ashish Kumar; Tapas Chandra Nag; Mahendra Kumar Thakur; Sunil Kumar Hota; Bhuvnesh Kumar
The original version of this article unfortunately contained mistake. The authors noticed that some anomalies in “Figure 5” of the manuscript. The figure for different timelines of hypoxic exposure was erroneously picked from the same folder which could be because of human error or uploading of wrong file during the compilation of results. The authors sincerely apologize for the inadvertent mistake and hereby publish the correct Figure 5. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Epigenetic Regulation of SNAP25 Prevents Progressive Glutamate Excitotoxicty in Hypoxic CA3 Neurons
(Humana Press Inc., 2017) Suryanarayan Biswal; Debashree Das; Kalpana Barhwal; Ashish Kumar; Tapas Chandra Nag; Mahendra Kumar Thakur; Sunil Kumar Hota; Bhuvnesh Kumar
Exposure to global hypoxia and ischemia has been reported to cause neurodegeneration in the hippocampus with CA3 neurons. This neuronal damage is progressive during the initial phase of exposure but maintains a plateau on prolonged exposure. The present study on Sprague Dawley rats aimed at understanding the underlying molecular and epigenetic mechanisms that lead to hypoxic adaptation of CA3 neurons on prolonged exposure to a global hypoxia. Our results show stagnancy in neurodegeneration in CA3 region beyond 14 days of chronic exposure to hypobaria simulating an altitude of 25,000 ft. Despite increased synaptosomal glutamate and higher expression of NR1 subunit of NMDA receptors, we observed decrease in post-synaptic density and accumulation of synaptic vesicles at the pre-synaptic terminals. Molecular investigations involving western blot and real-time PCR showed duration-dependent decrease in the expression of SNAP-25 resulting in reduced vesicular docking and synaptic remodeling. ChIP assays for epigenetic factors showed decreased expression of H3K9Ac and H3K14Ac resulting in SNAP-25 promoter silencing during prolonged hypoxia. Administration of sodium butyrate, a non-specific HDAC inhibitor, during 21 days hypoxic exposure prevented SNAP-25 downregulation but increased CA3 neurodegeneration. This epigenetic regulation of SNAP-25 promoter was independent of increased DNMT3b expression and promoter methylation. Our findings provide a novel insight into epigenetic factors-mediated synaptic remodeling to prevent excitotoxic neurodegeneration on prolonged exposure to global hypobaric hypoxia. © 2016, Springer Science+Business Media New York.