Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice
| Autor: | Tatyana A. Shelkovnikova, Wenbin Wei, Tetsuro Hirose, Camille Rabesahala de Meritens, Vsevolod Telezhkin, Johnathan Cooper-Knock, Natalia Ninkina, Vladimir L. Buchman, Shinichi Nakagawa, Michail S. Kukharsky, Haiyan An |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Central nervous system Regulator Biology Molecular neuroscience Article lcsh:RC321-571 Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Cellular stress response Adaptation Psychological Gene expression medicine Animals Premovement neuronal activity lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Neuroinflammation Mice Knockout Neurons Alternative splicing Cell biology Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Knockout mouse RNA Long Noncoding Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Vol 10, Iss 1, Pp 1-19 (2020) Translational psychiatry, 2020, Vol.10(1), pp.171 [Peer Reviewed Journal] |
| ISSN: | 2158-3188 |
| DOI: | 10.1038/s41398-020-0854-2 |
| Popis: | NEAT1 is a highly and ubiquitously expressed long non-coding RNA (lncRNA) which serves as an important regulator of cellular stress response. However, the physiological role of NEAT1 in the central nervous system (CNS) is still poorly understood. In the current study, we addressed this by characterising the CNS function of the Neat1 knockout mouse model (Neat1−/− mice), using a combination of behavioural phenotyping, electrophysiology and expression analysis. RNAscope® in situ hybridisation revealed that in wild-type mice, Neat1 is expressed across the CNS regions, with high expression in glial cells and low expression in neurons. Loss of Neat1 in mice results in an inadequate reaction to physiological stress manifested as hyperlocomotion and panic escape response. In addition, Neat1−/− mice display deficits in social interaction and rhythmic patterns of activity but retain normal motor function and memory. Neat1−/− mice do not present with neuronal loss, overt neuroinflammation or gross synaptic dysfunction in the brain. However, cultured Neat1−/− neurons are characterised by hyperexcitability and dysregulated calcium homoeostasis, and stress-induced neuronal activity is also augmented in Neat1−/− mice in vivo. Gene expression analysis showed that Neat1 may act as a weak positive regulator of multiple genes in the brain. Furthermore, loss of Neat1 affects alternative splicing of genes important for the CNS function and implicated in neurological diseases. Overall, our data suggest that Neat1 is involved in stress signalling in the brain and fine-tunes the CNS functions to enable adaptive behaviour in response to physiological stress. |
| Databáze: | OpenAIRE |
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