Hypersocialization, Social Blindness and Motor Deficits: the Role of PSD95 and PSD93 Rebecca Rocco
PSD95 and PSD93 are both membrane-associated guanylate kinase (MAGUK) proteins which are prominent and essential to glutaminergic postsynaptic terminal efficacy and function. Mutations of these proteins have been linked to the development of synaptopathies such as schizophrenia and autism (Yang et al., 2019, Coley et al., 2019). While PSD95 knockout animal models have shown that lack of PSD95 results in strange behaviours such as immobility, repetitive grooming, and heightened anxiety (Zhang et al., 2014), overall behaviour of these animal models has been difficult to assess due to motor impairment. In addition, the majority of genetic mutations within humans are in the heterozygous form, where a deficiency of a gene product is observed rather than a complete absence. Therefore, Winkler et al. (2018) investigated modified behaviour of PSD95 deficient mice. Furthermore, PSD93 knockout and deficient mice also had their behaviour investigated in order to assess whether PSD93 expression impairment results in similar behavioural phenotypes as in PSD95 deficiency, pointing to a potential shared functional and/or biological redundancy of PSD93/ PSD95. PSD95 deficient and wildtype C57BL/6J mice were raised and then subjected to a wide range of behavioural tests. PSD93 wildtype, deficient and knock-out mice were also investigated using a similar battery of behavioural tests. Mice were taken from each cohort to confirm genetic makeup and expression of PD genes using qPCR methods. This study found that PSD95 deficient mice showed hypersocial behaviours, only mild motor impairment and increased PSD93 expression within the hippocampus; males had increased aggression responding to foreign mice and females had increased vocalization responding to an anesthetized mouse. PSD93 knock-out mice showed comparable hypersocial behaviour to that of PSD95 deficient mice, as well as severe motor impairment. These results suggest that both PSD95 and PSD93 are implicated in social processing and behaviour. As PSD protein impairment has been implicated in the development of neuropsychiatric diseases (Gao et al., 2013), the use of PSD95 deficient mice as a model to study neuropsychiatric diseases which have social disinhibition symptoms associated with them may be beneficial. Key Words: Membrane-associated guanylate kinases (MAGUKs), Post synaptic density, PSD95, PSD93, schizophrenia, autism, synaptopathies, hippocampus, synaptic plasticity, genetic redundancy, social behaviour, social processing, social disinhibition, social blindness, hypersocialization
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