Neural stem cell properties and adult hippocampal neurogenesis in a knock-in mice model, expressing an autism-associated mutation.

Alteration of adult neurogenesis has been associated with neuropsychiatric disorders, including autism spectrum disorders (ASDs). Particularly, in the hippocampus of few ASD mice models, the properties of adult neural stem/progenitor cells (aNSPC) pool and the formation of new neurons have been found altered, suggesting a link between deregulated neurogenesis and some of the behavioural deficits found in these mice. In order to investigate neurogenesis in association to ASDs, we have been using the R451C Neuroligin3 (NLG3) knock-in mice, a model of a monogenic form of ASDs carrying the R451C substitution found in autistic patients. NLG3 is a postsynaptic protein involved in maturation, specification and plasticity of neural networks and the R451C knock-in mice display excitatory/inhibitory balance alterations in different brain regions, behavioural deficits, and structural brain abnormalities. We focused our study on the subgranular zone of the hippocampal dentate gyrus (DG), a neurogenic niche of the adult brain. Specifically, we compared proliferation and differentiation of new neurons between knock-in and wild-type mice, both in vivo and in vitro. In vitro data demonstrate that NSPC cultures derived from the DG of two-month-old knock-in mice contained a higher number of cells compared to the wild-type. However, BrdU cell number in the DGs was unchanged between KI and WT mice. In vivo data also show a decrease in the number of newly formed differentiated mature neurons (BrdU-NeuN double positive) in the hippocampus of the knock-in compared to wild-type mice. The mechanisms underlying the neurogenesis reduction in the knock-in mice are currently under investigation.