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Behavioural impairments in a mouse model of Kabuki syndrome associated with dopaminergic and neuroinflammatory
Thalles F Biondi1, Silvia M G Massironi2, Eduardo F Bondan1
1Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, São Paulo, Brazil.
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.
Insights
Kabuki syndrome model mice exhibit hyperactivity and stereotyped behaviors, linked to striatal dopaminergic hyperactivity and neuroinflammation. This research sheds light on the neurological underpinnings of Kabuki syndrome motor impairments.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Kabuki syndrome is a rare genetic disorder with diverse symptoms, including motor and behavioral deficits.
- Previous studies suggest motor impairments in Kabuki syndrome may involve dopaminergic pathways and neuroinflammation.
Purpose of the Study:
- To investigate the roles of striatal dopaminergic modulation and neuroinflammation in motor dysfunction in Kabuki syndrome.
- To utilize the Bapa mouse model to explore these hypotheses.
Main Methods:
- Assessed exploratory and stereotyped behaviors in Bapa and control mice.
- Quantified striatal expression of tyrosine hydroxylase (TH), GFAP, and Iba1.
Main Results:
- Bapa mice displayed exploratory hyperactivity and stereotyped behaviors.
- Elevated striatal TH, GFAP, and Iba1 levels were observed in Bapa mice.
Conclusions:
- Exploratory hyperactivity and stereotyped behaviors in Bapa mice correlate with striatal dopaminergic hyperactivity.
- A persistent neuroinflammatory process contributes to the observed motor and behavioral phenotypes in this Kabuki syndrome model.
