Differential Effects of Neonatal Ventral Hippocampus Lesion on Behavior and Corticolimbic Plasticity in Wistar-Kyoto and Spontaneously Hypertensive Rats.

Dysfunction of the corticolimbic system, particularly at the dendritic spine level, is a recognized core mechanism in neurodevelopmental disorders such as schizophrenia. Neonatal ventral hippocampus lesion (NVHL) in Sprague-Dawley rats induces both a schizophrenia-related behavioral phenotype and dendritic spine pathology (reduced total number and mature spines) in corticolimbic areas, which is mitigated by antipsychotics. However, there is limited information on the impact of rat strain on NVHL outcomes and antipsychotic effects. We compared the behavioral performance in the open field, novel object recognition (NORT), and social interaction tests, as well as structural neuroplasticity with the Golgi-Cox stain in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) male rats with and without NVHL. Additionally, we explored the effect of the atypical antipsychotic risperidone (RISP). WKY rats with NVHL displayed motor hyperactivity without impairments in memory and social behavior, accompanied by dendritic spine pathology in the neurons of the prefrontal cortex (PFC) layer 3 and basolateral amygdala. RISP treatment reduced motor activity and had subtle and selective effects on the neuroplasticity alterations. In SH rats, NVHL increased the time spent in the border area during the open field test, impaired the short-term performance in NORT, and reduced social interaction time, deficits that were corrected after RISP administration. The NVHL caused dendritic spine pathology in the PFC layers 3 and 5 of SH rats, which RISP treatment ameliorated. Our results support the utility of the NVHL model for exploring neuroplasticity mechanisms in schizophrenia and understanding pharmacotherapy.

A novel Golgi-Cox staining method for detecting and characterizing roles of the hepatic stellate cells in liver injury.

The aim of this study was to investigate the utility of the Golgi-Cox method to characterize the distribution and morphological changes of the hepatic stellate cells (HSCs) in CCl4 liver damaged rats. Six-week-old male Wistar rats were injected with CCl4 for ten weeks. The livers were processed with the Golgi-Cox method, reticuline, and Massons Trichrome stains, and analyzed under light microscopy. Histological evaluation of livers was made through the METAVIR score. In normal livers, the HSCs show stellate form with abundant thin cytoplasmic processes, distributed into hepatic lobule, mainly in zone 1. In addition, an intricate and broad network of fibers with radial distribution from the central vein to the periphery of the hepatic lobule was observed. In CCl4 damaged livers, with METAVIR score I and II, HSCs showed a moderate increase in the soma size, in the cytoplasmic processes and in density, distributed in zone 2 and 3; changes associated with a decrease in network fibers. In livers with METAVIR score III and IV, the morphology changes of the HSCs consisted of a significant increase in the soma size, cut and fraying appearance of the emerging cytoplasmic processes, and a decrease in HSCs density, distributed mainly in zone 3, with a significant depletion of network fibers. Results show that Golgi-Cox stain is able to impregnate the HSCs and could be an additional tool to study the morphological changes of the HSCs in the different experimental pathological conditions of the liver.

Dendritic morphology on neurons from prefrontal cortex, hippocampus, and nucleus accumbens is altered in adult male mice exposed to repeated low dose of malathion.

Malathion is a highly neurotoxic pesticide widely used in daily life. Acute and chronic toxicity from this organophosphorus compound may cause damage to health, especially to the central nervous system. In the present work, we show the effects of chronic exposure of malathion on dendritic morphology of neurons from prefrontal cortex (PFC), hippocampus, and nucleus accumbens (NAcc) in adult male mice. Animals were injected i.p. with low dose of malathion (40 mg/kg body weight) for 14 days. Control animals were injected with corn oil, used as vehicle. Fourteen days after the last injection, brains were removed and processed by the Golgi-Cox stain method, and coronal sections were obtained to perform Sholl analysis on pyramidal neurons from the PFC, CA1 area from the hippocampus, and medium spiny cells from the NAcc. Dendritic morphology analysis included the total dendritic length, the maximum branching order, and the dendritic spine density. Results indicated a significant decrement on dendritic morphology in neurons from the hippocampus and the PFC in animals injected with malathion, whereas medium spiny neurons from NAcc showed a significant decrement only on the dendritic spine density in malathion injected mice, as compared to control mice. These results suggest that chronic toxicity of malathion alters the dendritic morphology in adult age, which may affect behavior.

Alteration in dendritic morphology of cortical neurons in rats with diabetes mellitus induced by streptozotocin.

The animal model of streptozotocin-induced diabetes mellitus is used to study the changes produced by an increase in glucemia. The morphology of the pyramidal neurons of the prefrontal cortex, occipital cortex, and hippocampus was investigated in rats. The level of glucose in the blood was evaluated at 2 months, and the animals that exhibited more than 200 mg/dL were used. After 2 months of increasing blood-glucose level, the animals were sacrificed by an overdose of sodium pentobarbital and perfused intracardially with a 0.9% saline solution. The brains were removed, processed by the Golgi-Cox stain method, and analyzed by the Sholl method. Clearly, the rats with diabetes mellitus induced by streptozotocin showed a decrease in the dendritic length of pyramidal cells from all the analyzed regions (20% to 45%). Furthermore, the density of dendritic spines was decreased in all the pyramidal cells from the diabetic animals (36% to 58%). However, the pyramidal neurons of the CA1 hippocampus region were the most affected (58%). In addition, the Sholl analyses showed that the diabetic rats exhibited a decrease in the number of Sholl intersections when compared with the control group. The present results suggest that diabetes mellitus may in part affect the dendritic morphology in the limbic structures, such as prefrontal cortex, occipital cortex, and hippocampus, which are implicated in cognitive disorders.