Estradiol Regulates Polysialylated Form of the Neural Cell Adhesion Molecule Expression and Connectivity of O-LM Interneurons in the Hippocampus of Adult Female Mice.

The estrous cycle is caused by the changing concentration of ovarian hormones, particularly 17ß-estradiol, a hormone whose effect on excitatory circuits has been extensively reported. However, fewer studies have tried to elucidate how this cycle, or this hormone, affects the plasticity of inhibitory networks and the structure of interneurons. Among these cells, somatostatin-expressing O-LM neurons of the hippocampus are especially interesting. They have a role in the modulation of theta oscillations, and they receive direct input from the entorhinal cortex, which place them in the center of hippocampal function. In this study, we report that the expression of polysialylated form of the neural cell adhesion molecule (PSA-NCAM) in the hippocampus, a molecule involved in the plasticity of somatostatin-expressing interneurons in the adult brain, fluctuated through the different stages of the estrous cycle. Likewise, these stages and the expression of PSA-NCAM affected the density of dendritic spines of O-LM cells. We also describe that 17ß-estradiol replacement of adult ovariectomized female mice caused an increase in the perisomatic inhibitory puncta in O-LM interneurons as well as an increase in their axonal bouton density. Interestingly, this treatment also induced a decrease in their dendritic spine density, specifically in O-LM interneurons lacking PSA-NCAM expression. Finally, using an ex vivo real-time assay with entorhinal-hippocampal organotypic cultures, we show that this hormone decreased the dynamics in spinogenesis, altogether highlighting the modulatory effect that 17ß-estradiol has on inhibitory circuits.

Prenatal immune challenge induces behavioral deficits, neuronal remodeling, and increases brain nitric oxide and zinc levels in the male rat offspring.

Schizophrenia is a severe mental disorder with numerous etiological susceptibilities. Maternal infection is a key risk factor for schizophrenia. Prenatal lipopolysaccharide (LPS) infection stimulates cytokine production that affects brain development. In the present study, we aimed to investigate the effect of prenatal LPS injection at gestational day (GD) 14-16 on behavioral paradigms, and neuronal morphology in the prefrontal cortex (PFC), basolateral amygdala (BLA), nucleus accumbens (NAcc) and ventral hippocampus (VH) at two critical ages of development: pre-pubertal (postnatal day 35, PD35) and post-pubertal (PD60) age in male rats. We also evaluated the effects of LPS on nitric oxide (NO) and zinc (Zn) levels in seven brain areas (PFC, VH, amygdala, brainstem, striatum and dorsal hippocampus) at PD35 and PD60. LPS induced hyperlocomotion in a novel environment and reduced social contact as well as increased the levels of NO and Zn in the PFC, brainstem and amygdala as observed in other animal models of schizophrenia-related behavior. Furthermore, we found that LPS-treated rats presented post-pubertal neuronal hypertrophy in the PFC and BLA and decreased spine density in the NAcc. The neuronal morphology of neurons in the VH in LPS-treated rats remained unaltered. Interestingly, the anxiogenic-related behavior correlated with neuronal hypertrophy observed in the BLA. Our findings suggest that the behavioral and neural modifications observed in our model could be mediated by the long-lasting alterations in Zn and NO levels in the brain.