Behavioural impairments in a mouse model of Kabuki syndrome associated with dopaminergic and neuroinflammatory modulations

卡布奇综合征小鼠模型中的行为障碍与多巴胺能和神经炎症调节相关

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Abstract

OBJECTIVE: Kabuki syndrome is a rare multisystem congenital disorder characterised by specific facial malformations and several other symptoms, including motor impairments, increased susceptibility to infections, immune mediators' deficits, anxiety, and stereotyped behaviours. Considering the reports of motor impairments in Kabuki syndrome patients, the first hypothesis of the present study was that this motor dysfunction was a consequence of striatal dopaminergic modulation. The second hypothesis was that the peripheral immune system dysfunctions were a consequence of neuroinflammatory processes. To study these hypotheses, the mutant bapa mouse was used as it is a validated experimental model of Kabuki syndrome. METHODS: Exploratory behaviour, anxiety-like behaviour (light-dark test), repetitive/stereotyped behaviour (spontaneous and induced self-grooming), and tyrosine hydroxylase (TH), astrocyte glial fibrillary acidic protein (GFAP), and ionised calcium-binding adaptor molecule 1 (Iba1) striatal expressions were evaluated in female adult bapa and control mice. RESULTS: Female bapa mice did not present anxiety-like behaviour, but exploratory hyperactivity and stereotyped behaviour both on the spontaneous and induced self-grooming tests. Striatal TH, GFAP, and Iba1 expressions were also increased in bapa mice. CONCLUSION: The exploratory hyperactivity and the stereotyped behaviour occurred in detriment of the striatal dopaminergic system hyperactivity and a permanent neuroinflammatory process.

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