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•VPA- and PPA-induced autistic rat models present different behavioral performances.•VPA induces greater anxiety and cognitive deficits than PPA.•Prenatal Shank1,3/BDNF expression differences correlated to autism-like behaviors.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder featuring altered neuronal circuitry and consequently impaired social interactions, restrictive interests plus repetitive stereotypic activities. In the present study, differentiated behaviors of valproic (VPA) and propionic (PPA) acid-mediated autism rats were correlated to cerebral scaffolding proteins (Shank1,3) and BDNF expression variations. Sprague–Dawley offspring that received VPA during pregnancy displayed a notably diminished permanence (−78 %, p < 0.01) in the light chamber of light dark (LD) test, reduced exploratory tasks, i.e. grooming (−90 %) and rearing (−65 %). Moreover, they executed extremely greater climbing intervals (+300 %, p < 0.001) in novel cage (NC) test, plus exhibited an extremely reduced (−331 %) discrimination index in novel object recognition (NOR) test when compared to controls. PPA-treated postnatal days (PND) 12–16 rats also displayed anxiety-like behaviors, although in a less evident manner, as indicated by a moderate time (+55 %; p < 0.05) spent in dark chamber along with notable and moderate decreases in digging (−78 %) plus grooming (−52 %), respectively. Contextually, VPA- more than PPA supplied opposite Shank1,3 expression changes in cerebellum (CB; −62 %; +78 %), dorsomedial prefrontal cortex (DM-PFC; +95 % −76 %), respectively, while resulting extremely upregulated in hippocampus (HIP; +125 % – +155 %). Even BDNF resulted to be substantially and notably diminished in HIP (−85 %) and DM-PFC (−72 %), respectively, of VPA rats while it was only moderately reduced (−35 % to −45 %) in these same areas of PPA rats. The early altered brain-specific expression levels accounting for different behavioral performances may provide useful diagnostic indications and constitute valuable therapeutic strategies for autistic patients.