Parvalbumin (PV) is a calcium-binding protein expressed in a subpopulation of mostly GABAergic neurons in several brain regions, e.g. cortex and striatum. A reduction in the number of PVimmunopositive (PV+ ) neurons or a decrease in the intensity of PV immunoreactivity was reported in several mouse models of autism spectrum disorders (ASD) including mice with mutations in Shank genes. We have previously shown that the absence or reduction of PV in PV-/- and PV+/- mice, respectively, leads to a robust ASDlike phenotype, evidenced by all core symptoms including impairment in social interaction and communication, as well as repetitive and stereotyped patterns of behavior. We investigated whether the “reduction in PV+ neurons” in knockout mice for Shank1, Shank3 and PV+/- mice was the result of a decrease in PV expression levels and/or partial loss of the PVergic neuron subpopulation. We applied stereological methods to estimate the number of PVergic neurons in ASD-associated brain regions of PV-/-, PV+/-, Shank1-/- and Shank3B-/- mice. Vicia Villosa Agglutinin (VVA) was used to identify the specific extracellular matrix components enwrapping PVergic neurons. Quantitative levels of PV protein and Pvalb mRNA were analyzed by Western blot analyses and qRT-PCR, respectively. The analyses of cell numbers in different brain regions revealed that the observed “reduction of PV+ neurons” resulted from a reduction in Pvalb mRNA and PV protein. The unaltered numbers of VVA+ neurons are not compatible with a PV cell decrease/loss in these ASD models. We hypothesize that the down-regulation of PV in PVergic networks leads to an impairment of the excitation/inhibition balance and might signify a convergent downstream endpoint for some forms of ASD. Restoring of normal PV protein levels and/ or of PV+ neuron function might serve as a novel therapeutic strategy to avoid and/or possibly reverse the ASD phenotype.
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