Overexpression of serotonin receptor 5b expression rescues neuronal and behavioral deficits in a mouse model of Kabuki syndrome
| Autor: | Ya-Jie Xu, Zhao-Qian Teng, Gang-Bin Tang, Ting-Wei Mi, Jun Gao, Saijilafu, Hong-Zhen Du, Chang-Mei Liu, Man-Lian Sun, Shu-Guang Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Hippocampal formation Biology Neurotransmission Anxiety Article lcsh:RC321-571 03 medical and health sciences 0302 clinical medicine UTX Memory Conditional gene knockout medicine Synaptic transmission Receptor lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry 5-HT receptor G protein-coupled receptor Kabuki syndrome General Neuroscience Long-term potentiation medicine.disease 030104 developmental biology Neuroscience 030217 neurology & neurosurgery 5-HT5B |
| Zdroj: | IBRO Reports, Vol 9, Iss, Pp 138-146 (2020) IBRO Reports |
| ISSN: | 2451-8301 |
| Popis: | 5-hydroxytryptamine receptor 5B (5-HT5B) is a gene coding for a G protein-coupled receptor (GPCR) that plays key roles in several neurodevelopmental disorders. Our previous study showed that disruption of 5-HT5B induced by lysine (K)-specific demethylase 6A (Kdm6a, also known as Utx) conditional knockout (cKO) in mouse hippocampus was associated with cognition deficits underlying intellectual disability in Kabuki syndrome (KS), a rare disease associated with multiple congenital and developmental abnormalities, especially neurobehavioral features. Here we show that Utx knockout (KO) in cultured hippocampal neurons leads to impaired neuronal excitability and calcium homeostasis. In addition, we show that 5-HT5B overexpression reverses dysregulation of neuronal excitability, intracellular calcium homeostasis, and long-term potentiation (LTP) in cultured Utx KO hippocampal neurons and hippocampal slices. More importantly, overexpression of 5-HT5B in Utx cKO mice results in reversal of abnormal anxiety-like behaviors and impaired spatial memory ability. Our findings therefore indicate that 5-HT5B, as a downstream target of Utx, functions to modulate electrophysiological outcomes, thereby affecting behavioral activities in KS mouse models. |
| Databáze: | OpenAIRE |
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