[feed] Atom [feed] RSS 1.0 [feed] RSS 2.0

Jamal, I and Kumar, V and Vatsa, N and Shekhar, S and Singh, BK and Sharma, A and Jana, NR (2017) Rescue of altered HDAC activity recovers behavioural abnormalities in a mouse model of Angelman syndrome. Neurobiology of Disease, 105. pp. 99-108.

4). Imran-2017.pdf

Download (3224Kb) | Preview


Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe intellectual and developmental disabilities. The disease is caused by the loss of function of maternally inherited UBE3A, a gene that exhibits paternal-specific imprinting in neuronal tissues. Ube3a-maternal deficient mice (AS mice) display many classical features of AS, although, the underlying mechanism of these behavioural deficits is poorly understood. Here we report that the absence of Ube3a in AS mice brain caused aberrant increase in HDAC1/2 along with decreased acetylation of histone H3/H4. Partial knockdown of Ube3a in cultured neuronal cells also lead to significant up-regulation of HDAC1/2 and consequent down-regulation of histones H3/H4 acetylation. Treatment of HDAC inhibitor, sodium valproate, to AS mice showed significant improvement in social, cognitive and motor impairment along with restoration of various proteins linked with synaptic function and plasticity. Interestingly, HDAC inhibitor also significantly increased the expression of Ube3a in cultured neuronal cells and in the brain of wild type mice but not in AS mice. These results indicate that anomalous HDAC1/2 activity might be linked with synaptic dysfunction and behavioural deficits in AS mice and suggests that HDAC inhibitors could be potential therapeutic molecule for the treatment of the disease.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Dr. D.D. Lal
Date Deposited: 11 Jan 2018 09:43
Last Modified: 18 May 2018 10:17
URI: http://nbrc.sciencecentral.in/id/eprint/319

Actions (login required)

View Item View Item