Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for CALCITONIN GENE– RELATED PEPTIDE (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents. Ann Neurol 1999;45:207–215

Exposure to prenatal stress (PS) increases the risk of developing neurobehavioral disturbances later in life. Previous work has shown that exercise can exert beneficial effects on brain damage; however, it is unknown whether voluntary wheel running (VWR) can ameliorate the neurobehavioral impairments induced by PS in adolescent offspring. Pregnant CF-1 mice were randomly assigned to control (n=5) or stressed (n=5) groups. Pregnant dams were subjected to restraint stress between gestational days 14 and 21 (G14-21), whereas controls remained undisturbed in their home cages. On postnatal day 21 (P21), male pups were randomly assigned to the following experimental groups: control (n=5), stressed (n=5), and stressed mice+daily submitted to VWR (n=4). At P52, all groups were behaviorally evaluated in the Morris water maze. Animals were then sacrificed, and Golgi-impregnated granule cells were morphometrically analyzed. The results indicate that PS produced significant behavioral and neuronal impairments in adolescent offspring and that VWR significantly offset these deleterious effects.

Social isolation in rodents is the most well characterized animal model for early stressful experiences and their neurobehavioral consequences. The present study analyzed the effects of early social isolation on the expression of the calcium binding protein calbindin-D28k (CAD) and dendritic arborization in the medial prefrontal cortex (mPFC) of the rat. Sprague-Dawley male rats were reared either under isolation or social conditions from 21 to 51 postnatal days. At the end of this period the animals were behaviorally evaluated in the open-field test, sacrificed, and mPFC serial sections were processed either for immunocytochemical labeling against CAD or Golgi-Cox-Sholl staining. Isolated-reared rats exhibited a dramatic decrease in the number of CAD immunoreactive neurons and a significant dendritic atrophy of layer II/III pyramidal cells in association with a reduced exploratory behavior.

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The present study investigates the effects of early sensorimotor stimulation on behavioral and neuronal cytodifferentiation in motor and visual cortex of lactating rats. Seventy-two male and female Sprague-Dawley albino rats were systematically submitted to environmental stimulation during the early postnatal period (postnatal days 5–21). On postnatal day 22, four behavioral tests were performed (open field, narrow path crossing, hind limb support and ascending on a rope). In order to evaluate dynamic neuronal changes induced by sensorimotor enrichment, brains were stained through the Golgi-Cox-Sholl method. Morphometric studies were carried out in pyramidal neurons located in motor and visual cortical layers II and III, by measuring their basal dendritic length and branching. Further, wide cortical field studies were performed with the aim of evaluating the degree of development reached by clusters of pyramidal cells. The results indicate that sensorimotor stimulation carried out during the suckling period produced a significant increase in neuronal cytodifferentiation as observed in single cell studies. However, collective neuronal evaluations yielded less significant results. Consistently, rats exposed to enriched environments showed a better performance in behavioral adaptive responses.

Sprague-Dawley albino rats were subjected to an experimental paradigm in which environmental and nutritional variables were studied from birth to day 18. The use of Golgi-Cox-Sholl methodology allowed quantitative evaluations of neurons which were randomly impregnated with metallic mercury after fixation in a mercury salt. The nutritional treatment employed did not significantly influence the cytoplasmatic differentiation of cortical neurons although it was able to induce gross morphological modifications in body weight and size. By contrast, an impoverished surrounding during a limited period of time had a profound effect on the basal dendritic tree. The evidence presented here suggests the importance of the preweaning environment on the development of neural appendages. Motor pyramids of pups housed in deteriorated conditions underwent a progressive decrement in the length and number of peripheral branches and terminal dendrites. A decreased rate of cortical differentiation was also observed in overnourished pups as a result of reducing the litter size. This regressive event, can probably be attributed to social and sensory-motor limitations ofthe experimental group. However, to confirm this possibility, further research is required.

Clinical and preclinical studies have demonstrated that prenatal stress (PS) induces neuronal and behavioral disturbances in the offspring. In the present study, we determined whether maternal voluntary wheel running (VWR) during pregnancy could reverse the putative deleterious effects of PS on the neurodevelopment and behavior of the offspring. Pregnant CF-1 mice were randomly assigned to control, restraint stressed or restraint stressed+VWR groups. Dams of the stressed group were subjected to restraint stress between gestational days 14 and delivery, while control pregnant dams remained undisturbed in their home cages. Dams of the restraint stressed+VWR group were subjected to exercise between gestational days 1 and 17. On postnatal day 23 (P23), male pups were assigned to one of the following experimental groups: mice born from control dams, stressed dams or stressed+VWR dams. Locomotor behavior and pyramidal neuronal morphology were evaluated at P23. Animals were then sacrificed, and Golgi-impregnated pyramidal neurons of the parietal cortex were morphometrically analyzed. Here, we present two major findings: first, PS produced significantly diminished dendritic growth of parietal neurons without altered locomotor behavior of the offspring; and second, maternal VWR significantly offset morphological impairments.

A number of clinical studies suggest that prenatal stress can be a risk factor in the development of various psychopathologies, including schizophrenia, depression, anxiety, and autism. The cerebellar vermis has been shown to be involved in most of these disorders. In the present study, therefore, we evaluate the effect of maternal stress on long-term alterations in vermal Purkinje cell morphology. Furthermore, to discern whether these structural changes are associated with anxious behavior, the exploratory drive in the elevated plus maze was evaluated. Pregnant CF-1 mice were randomly assigned to control (n = 14) or stressed (n = 16) groups. Dams of the stressed group were subjected to restraint stress between gestational days 14 and 20, while control pregnant dams remained undisturbed in their home cages. Anxious behavior and Purkinje cell morphology were evaluated in three ontogenetic stages: postweaning, adolescence, and adulthood. Although exploratory behavior in the elevated plus maze was unaffected by prenatal stress, the Purkinje cell morphology showed a transient period of abnormal growth (at postweaning and juvenile stages) followed by dramatic dendritic atrophy in adulthood. In conclusion, prenatal stress induced significant long-lasting bimodal changes in the morphology of vermal Purkinje cells. These structural alterations, however, were not accompanied by anxious behaviors in the elevated plus maze.