Prenatal valproate treatment produces autistic-like behavior and increases metabotropic glutamate receptor 1A-immunoreactivity in the hippocampus of juvenile rats

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social communication and social interaction, and repetitive and stereotypical patterns of behavior. Previously, a common physiopathological pathway, involving the control of synaptic protein synthesis, was proposed as a convergence point in ASD. In particular, a role for local mRNA translation activated by class I metabotropic glutamate receptor type 5 (mGluR5) was suggested in genetic syndromes with autistic signs and in the prenatal exposition to the valproate model of autism. However, the role of the other members of class I metabotropic glutamate receptors, including mGluR1, has been poorly studied. The present study analyzed the immunoreactivity for mGluR1a in the hippocampus of rats prenatally treated with valproate. Pregnant dams (embryonic day 12.5) were injected with valproate (450 mg/kg) and subsequently, the behavior and mGluR1a were evaluated at postnatal day 30. Experimental rats exhibited social deficit, repetitive conduct and anxious behaviors compared with that of the control animals. Additionally, the present study observed an increased level of mGluR1a-immunoreactivity in the hilus of dentate gyrus and in the CA1 alveus region of the hippocampus. These results suggested an over‑functioning of mGluR1a signaling in the hippocampus, induced in the valproate model of autism, which may serve a role in cognitive and behavioral signs of ASD.

Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism

“…It was reported that neural projections have been identified between the amygdala and hippocampus and between the ventral tegmental area and nucleus accumbens and alteration of sociability occurred after stimulation of these projections (Allsop et al, 2014;Calhoon and Tye, 2015). Moreover, over-functioning of mGluR1a signaling in the hippocampus accompanied with autistic-like behavior were found in prenatal VPAexposed juvenile rats (Peralta et al, 2016). Taken together, these findings show that the hippocampus plays an important role in social deficit in VPA-induced autism model.…”

Effects of PM2.5 and gases exposure during prenatal and early-life on autism–like phenotypes in male rat offspring

“…Typically, a wild type animal will spend a significant amount of time in the compartment with the stranger compared to the compartment with empty cup. Such behavior indicates normal sociability, social motivation, and affiliation [35,36]. In the sociability session of the test, every group demonstrated a significant preference for spending time in the chamber containing stranger1 compared to the empty chamber.…”

Region-Specific Reduction of BDNF Protein and Transcripts in the Hippocampus of Juvenile Rats Prenatally Treated With Sodium Valproate

“…Several studies, including our recent report (Peralta et al, 2016), have indicated that treatment of rats with a single dose of sodium valproate at gestational day 12.5 triggers some behavioral alterations which resemble those observed in autism; i.e., social deficit, anxiety and repetitive behaviors. In the present study, and using the VPA-model in Sprague–Dawley rats, we have found autism-like behaviors that were associated with a reduction in BDNF transcripts containing the long-3′UTR in the inferior blade of the DG and in the polymorphic layer of the CA3 region.…”

“…Social behavior and anxiety were analyzed at PN30 using the three-chamber social test and elevated plus maze test, respectively; as we have previously shown (Peralta et al, 2016). For the social test, total interaction time was 10 min and control and experimental animals were exposed to a familiar congener located in one of the lateral chambers inside of a wire cage, while the other chamber remained empty.…”

“…Coronal sections equivalent to those used in the ISH protocol were destined for BDNF immunoreactivity detection by free-floating Immunohistochemistry (IHC), using a previously described procedure (Peralta et al, 2016). Briefly, endogenous peroxidase was blocked by incubation with 0.3% H 2 O 2 during 45 min, and sections were incubated overnight at room temperature with primary antibody (1:100 polyclonal anti-BDNF, Santa Cruz, CA, USA) in blocking solution (3% BSA, 0.4% Triton X-100 PBS).…”