Publications by authors named "Unis Ahmad Bhat"

4 Publications

  • Page 1 of 1

Prenatal stress effects on offspring brain and behavior: Mediators, alterations and dysregulated epigenetic mechanisms.

J Biosci 2021 ;46

CSIR- Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad 500 007, India.

Prenatal environment significantly influences mammalian fetal development and adverse conditions have life-long consequences for the offspring health. Research has revealed that a wide variety of prenatal stress factors lead to increased risk of vulnerability to neuropsychiatric disorders in the individuals. Multiple mediators are involved in stress transfer from mother to the developing fetus, with stress hormone cortisol being a chief player. Further, the developmental programming effects of prenatal stress have been observed in the form of alterations in the offspring brain at different levels. This review covers stress transfer mediators such as cortisol, serotonin, maternal cytokines, reactive oxygen species (ROS) and the maternal microbiota, and their role in fetal programming. Prenatal stress leads to alterations in the offspring brain at multiple levels, from molecular and cellular to structural. These alterations eventually result in lasting phenotypic alterations such as in the offspring behavior and cognition. Different brain alterations induced by prenatal stress such as in neural pruning processes, neural circuit formation, brain structural connectivity and epigenetic systems regulating neural gene expression are under focus in the second part of the review. The latter constitutes a key molecular mechanism involved in prenatal stress effects and has been discussed in more detail.
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January 2021

Gene Expression Analysis Identifies Cholesterol Metabolism Dysregulation in Hippocampus of Phenytoin-Resistant Pentylenetetrazol-Kindled Epileptic Mice.

Neuromolecular Med 2021 Feb 18. Epub 2021 Feb 18.

Epigenetics & Neuropsychiatric Disorders Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Habsiguda, Hyderabad, Telangana State, 500007, India.

Pharmaco-resistant Epilepsy has been a major challenge for medical interventions in controlling seizures. To date, up to 33% of the patients with epilepsy do not show adequate response to anti-epileptic drugs even after prolonged combinatorial drug usage. Using microarray, this study explores the changes in hippocampal gene expression in the phenytoin-resistant pentylenetetrazol (PTZ)-kindled mouse model of epilepsy. Our results from mRNA microarray analysis show distinct gene expression profiles in the hippocampus of phenytoin-resistant and sensitive mice. Pathway enrichment analysis showed differential expression of genes involved in cholesterol biosynthesis in phenytoin-resistant and sensitive mice.
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http://dx.doi.org/10.1007/s12017-021-08648-0DOI Listing
February 2021

Advances in histone deacetylase inhibitors in targeting glioblastoma stem cells.

Cancer Chemother Pharmacol 2020 08 7;86(2):165-179. Epub 2020 Jul 7.

CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, 500007, Telangana, India.

Glioblastoma multiforme (GBM) is a lethal grade IV glioma (WHO classification) and widely prevalent primary brain tumor in adults. GBM tumors harbor cellular heterogeneity with the presence of a small subpopulation of tumor cells, described as GBM cancer stem cells (CSCs) that pose resistance to standard anticancer regimens and eventually mediate aggressive relapse or intractable progressive GBM. Existing conventional anticancer therapies for GBM do not target GBM stem cells and are mostly palliative; therefore, exploration of new strategies to target stem cells of GBM has to be prioritized for the development of effective GBM therapy. Recent developments in the understanding of GBM pathophysiology demonstrated dysregulation of epigenetic mechanisms along with the genetic changes in GBM CSCs. Altered expression/activity of key epigenetic regulators, especially histone deacetylases (HDACs) in GBM stem cells has been associated with poor prognosis; inhibiting the activity of HDACs using histone deacetylase inhibitors (HDACi) has been promising as mono-therapeutic in targeting GBM and in sensitizing GBM stem cells to an existing anticancer regimen. Here, we review the development of pan/selective HDACi as potential anticancer agents in targeting the stem cells of glioblastoma as a mono or combination therapy.
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http://dx.doi.org/10.1007/s00280-020-04109-wDOI Listing
August 2020

Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication.

Biochim Biophys Acta Mol Basis Dis 2017 01 21;1863(1):152-164. Epub 2016 Sep 21.

CSIR-Centre for Cellular and Molecular Biology (CCMB), Habsiguda, Uppal Road, Hyderabad 500007, India. Electronic address:

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/local administration of histone deacetylase inhibitors. However, the role of other epigenetic mechanisms such as histone lysine methylation and demethylation in stroke-induced damage and subsequent recovery process is elusive. Here, we established an Internal Carotid Artery Occlusion (ICAO) model in CD1 mouse that resulted in mild to moderate level of ischemic damage to the striatum, as suggested by magnetic resonance imaging (MRI), TUNEL and histopathological staining along with an evaluation of neurological deficit score (NDS), grip strength and rotarod performance. The molecular investigations show dysregulation of a number of histone lysine methylases (KMTs) and few of histone lysine demethylases (KDMs) post-ICAO with significant global attenuation in the transcriptionally repressive epigenetic mark H3K9me2 in the striatum. Administration of Dimethyloxalylglycine (DMOG), an inhibitor of KDM4 or JMJD2 class of histone lysine demethylases, significantly ameliorated stroke-induced NDS by restoring perturbed H3K9me2 levels in the ischemia-affected striatum. Overall, these results highlight the novel role of epigenetic regulatory mechanisms controlling the epigenetic mark H3K9me2 in mediating the stroke-induced striatal damage and subsequent repair following mild to moderate cerebral ischemia.
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http://dx.doi.org/10.1016/j.bbadis.2016.09.014DOI Listing
January 2017
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