Prenatal exposure to propionic acid induces altered locomotion and reactive astrogliosis in male rats.

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by movement and social deficits with rapidly increasing incidence worldwide. Propionic acid (PPA) is a histone deacetylase inhibitor that regulates neuronal plasticity in the brain. Evaluation of the behavioral and cellular consequences of PPA exposure during a critical neurodevelopmental window is required. Therefore, in the present study we aimed to evaluate the effects of prenatal PPA exposure on locomotor behavior and astrocyte number, as well as on levels of nitric oxide (NO), synaptophysin (SYP; a marker of synaptic plasticity), and metallothionein 3 (MT-III; a marker of reactive oxygen species and zinc metabolism), in the prefrontal cortex (PFC) of male rats. All parameters were evaluated at three critical ages of development: postnatal days (PD) 21 (weaning age), PD35 (pre-pubertal age) and PD70 (post-pubertal age). Prenatal PPA exposure induced hypolocomotion and decreased rearing events at weaning age. Moreover, astrogliosis in the PFC was observed in PPA-treated rats at pre- and post-pubertal age. SYP levels were dramatically decreased in PPA-treated rats with simultaneous astrogliosis, suggesting reduced synaptic plasticity. MT-III expression was deregulated in PPA-treated rats. Finally, the expression of NO in the PFC remained unaltered in PPA-treated rats. These results mimic behavioral, neuronal and astrocytic characteristics observed in ASD patients.

Changes in nitric oxide, zinc and metallothionein levels in limbic regions at pre-pubertal and post-pubertal ages presented in an animal model of schizophrenia.

Recent data suggest that rats with neonatal ventral hippocampal lesion (NVHL) show changes related to inflammatory processes and oxidative stress at the prefrontal cortex (PFC) level at post-pubertal age. The NVHL model is considered an animal model in schizophrenia. Here we analyzed the levels of nitrite, zinc, and metallothionein (MT) in cortical and subcortical regions of NVHL rats at pre-pubertal and post-pubertal ages. Nitric oxide (NO) levels were evaluated through measurement of nitrite levels. The locomotor activity was also evaluated in a novel environment. Animals with NVHL showed an increase in locomotor activity only at post-pubertal age. Furthermore, at pre-pubertal age, NVHL rats showed an increase in NO levels in ventral and dorsal hippocampus, thalamus, Caudate-putamen (CPu) and brainstem, in zinc levels in ventral and dorsal hippocampus, and CPu, and the MT level also in the ventral hippocampus and occipital cortex. In addition, at pre-pubertal age, a reduction in MT levels was also found in the PFC, parietal and temporal cortices, the CPu and the cerebellum. However, after puberty, NVHL caused an increase in NO levels in the PFC, and also zinc levels in the PFC and occipital and parietal cortices, with a reduction in MT levels in the thalamus and NAcc. Our results show the changes of these three molecules over time, among lesion (PD7), pre-pubertal and post-pubertal ages. This suggests changes at pre-pubertal age directly related to the site of the lesion, while at post-pubertal age, our data highlight changes in the PFC, a region mainly involved in schizophrenia.