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

Abstract

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.