Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities.

Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model.

Effect of excitotoxic lesions of the neonatal ventral hippocampus on the immobility response in rats.

Rats with neonatal ventral hippocampal (nVH) lesions show postpubertal hypersensitivity to dopamine agonists, which may be reversed by neuroleptic treatment. In addition, the immobility response (IR) may be regulated by dopaminergic activity. We investigated the influence of the IR caused by clamping the neck of rats that had received bilateral ibotenic acid lesions of the ventral hippocampus at postnatal day 7 (PD7). At both ages, prepubertal (PD35) and postpubertal (PD56), the duration of the IR was significantly increased in animals with lesions when compared to controls. These findings indicate that nVH damage results in behavioral changes, such as enhancement of the IR, related to mesolimbic dopaminergic transmission.

Anoxia at birth induced hyperresponsiveness to amphetamine and stress in postpubertal rats.

Several evidences suggest that transient global anoxia after Caeraean section birth in rats produces behavioral changes related to dopaminergic transmission. However, all of the reports tested the behavioral changes in adult rats. Here we investigated the role of perinatal anoxia on behavioral paradigms related to dopamine (DA) such as novel environment, saline injection, D-amphetamine, apomorphine and stress-induced changes in locomotor activity at prepubertal and postpubertal ages. All these dimensions of behavior can be affected in schizophrenia. Caesarean section birth with or without an additional period of anoxia was performed in Sprague-Dawley rats and their behaviors were studied at P35 and P56, respectively. In addition, a third group of animals born vaginally served as control. No significant differences in saline injection and D-amphetamine-induced locomotion were observed when the three groups of rats at P35 were compared. However, stress-induced locomotor activity was significantly increased in the Caesarean birth plus anoxia at P35, while after puberty (at P56), saline injection, D-amphetamine and stress-induced locomotion were significantly enhanced in the Caesarean birth plus anoxia compared to its control groups. The data suggests that anoxia at birth mediates differently the functional development and maturation of DA behaviors in adult rats.

Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats.

The effects of postweaning social isolation (pwSI) on the morphology of the pyramidal neurons from the medial part of the prefrontal cortex (mPFC) and hippocampus were investigated in rats. The animals were weaned on day 21 postnatal (P21) and isolated 8 weeks. After the isolation period, locomotor activity was evaluated through 60 min in the locomotor activity chambers and the animals were sacrificed by overdoses of sodium pentobarbital and perfused intracardially with 0.9% saline solution. The brains were removed, processed by the Golgi-Cox stain and analyzed by the Sholl method. The locomotor activity in the novel environment from the isolated rats was increased with respect to the controls. The dendritic morphology clearly showed that the pwSI animals presented a decrease in dendritic length of pyramidal cells from the CA1 of the hippocampus without changes in the pyramidal neurons of the mPFC. However, the density of dendritic spines was decreased in the pyramidal cells from mPFC and Hippocampus. In addition, the Sholl analyses showed that pwSI produced a decrease in the number of sholl intersections compared with the control group only in the hippocampus region. The present results suggest that pwSI may in part affect the dendritic morphology in the limbic structures such as mPFC and hippocampus that are implicated in schizophrenia.

Comparative behavioral changes between male and female postpubertal rats following neonatal excitotoxic lesions of the ventral hippocampus.

Neonatal ventral hippocampal (nVH) lesioned male rat has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. There are significant gender differences in schizophrenia with male and female individuals differing in the age of onset, course and outcome of the disorder. In order to assess whether the behavioral effects of nVH lesions extend to or are different in female rats, we investigated spontaneous locomotion, grooming, social interactions and spatial memory in male and female rats post-pubertally at postnatal day (P) 56 following bilateral ibotenic acid of the ventral hippocampus at P7. The spontaneous locomotor activity in a novel environment of both male and female nVH lesioned rats was significantly enhanced compared to their respective sham-operated controls. In tests of social interactions, the number of encounters was significantly decreased in female lesioned rats, whereas the male nVH lesioned rats showed a significantly reduced duration of active social interactions. Furthermore, Morris water maze test showed a deficit of spatial learning/memory in only male lesioned rats with significant decrease in the latency to find hidden platform. These results suggest that while nVH lesions affect post-pubertal behavior in both sexes of rats, the males appear to be affected to a greater extent than the females underscoring the influence of sex differences in the development of behaviors in the nVH lesioned animals.

Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats.

The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

Neonatal prefrontal cortex lesion using CO2 laser technique.

Prefrontal cortex (PFC) is a large area of the brain and its neonatal lesion with ibotenic or kainic acid is used to study the early abnormalities in neurodevelopment that lead to behavioral changes linked to schizophrenia. However, these exitotoxic drugs produce a large and asymmetric damage in the PFC. We produced the bilateral lesions of the dorsal part of the PFC of neonatal Sprague-Dawley rats (postnatal day 7, P7) at the anteroposterior +2.5 mm and mediolateral +/-0.4 coordinates by the new laser technique that employ the confined radiation of the CO(2) laser in the pulsed mode. The laser was used because its coherent radiation can be focused in a very small spot and as small as of several tens of micrometers in diameters. The CO(2) laser radiation is strongly absorbed by water that is present in any soft tissue. Thereafter, the configuration of the heated zone and, consequently, that of the lesion does not depend on the morphological non-homogeneity of particular structures. We obtained the symmetric, conical in shape and small-size bilateral lesions of the PFC. The size of the lesion depended on the beam spot-size and could be as small as several dozens of micrometers in diameter. Our data suggests that the laser technique will be used for the anatomical-functional studies of the PFC in the brain.

Neonatal caffeine administration causes a permanent increase in the dendritic length of prefrontal cortical neurons of rats.

We studied the morphological changes of the dendritic length of the pyramidal neurons of the prefrontal cortex (PFC) induced by the effect of chronic administration of caffeine in the neonatal rat. The caffeine (50 mg/kg, s.c.) was injected from day 1 after birth (P1) to day 12 (P12). The morphology of the pyramidal neurons of layer 3 of the PFC was investigated in these animals at two different ages, before puberty (P35) and after puberty (P70). Before the animals were sacrificed by using overdoses of sodium pentobarbital and being perfused intracardially with 0.9% saline, the locomotor activity in a novel environment was measured. The brains were then removed, processed by the Golgi-Cox stain, and analyzed by the Sholl method. The dendritic morphology clearly showed that the neonatal animals administered caffeine showed an increase in the dendritic length of the pyramidal neurons of the PFC when compared with the control animals at both ages. The present results suggest that neonatal administration of caffeine may in part affect the dendritic morphology of the pyramidal cells of this limbic structure and this effect persists after puberty and may be implicated in several brain processes.

Comparative behavioral changes in postpubertal rats after neonatal excitotoxic lesions of the ventral hippocampus and the prefrontal cortex.

The neonatal ventral hippocampal (nVH) and the neonatal prefrontal cortex (nPFC) lesions in rats have been used as models to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. We investigated the role of the nVH and the nPFC lesions on behavioral characteristics related to locomotor behaviors, social interaction, and grooming. Bilateral ibotenic acid lesions of the VH, the PFC, or both were made in neonatal Sprague-Dawley rats (postnatal day 7, P7) and their behaviors studied at P35 and P60. No significant differences in any of the behaviors were observed between sham animals and rats with ibotenic acid lesions at P35. Postpubertally (at P60), the spontaneous locomotor activity of nVH-lesioned rats was significantly enhanced compared to the sham controls; however, this hyperactivity was reversed by nVH and nPFC double lesions. Neonatal PFC lesion alone did not alter spontaneous activity, although a trend of increased activity was observed. The duration of grooming was significantly decreased in rats with neonatal lesions of the VH. Similar to the data on locomotion, nVH plus nPFC lesion normalized the grooming behavior. Lesion of the PFC alone was without any significant effect on grooming behavior. Neonatal VH-lesioned animals spent less time in active social interaction, and this effect persisted even in nVH plus nPFC-lesioned animals. By itself, nPFC lesion did not alter social behavior. These data suggest that subtle developmental aberrations within PFC caused by nVH lesions, rather than the lesion of PFC itself, may contribute to some of the behavioral changes seen in the nVH-lesioned rats.