17beta-Estradiol-induced remodeling of GABAergic axo-somatic synapses on estrogen receptor expressing neurons in the anteroventral periventricular nucleus of adult female rats.

Experimental data demonstrate that the nervous system is widely influenced by sex hormones and the brain is continuously shaped by the changing hormone milieu throughout the whole life. Earlier we demonstrated that on the effect of estradiol there is a cyclic synaptic remodeling, i.e. a transient decrease in the number of GABAergic axo-somatic synapses in the arcuate nucleus. By using preembedding estrogen receptor and postembedding GABA immunostaining, in the present paper we studied the specificity of this effect and we found that in the anteroventral periventricular nucleus (AvPv) of adult female rats 17beta-estradiol treatment does not affect all synapses and neurons. In contrast to the arcuate nucleus, hormonal treatment induces a significant increase of inhibitory axo-somatic synapses in the AvPv and we found selectivity at the level of the postsynaptic neurons, as well. We analyzed the hormone-induced synaptic remodeling in estrogen receptor alpha and beta immunoreactive and non-labeled cells and the change in synapse number was observed only in neurons which express estrogen beta receptor.

Behavioral effects of subchronic inorganic manganese exposure in rats.

BACKGROUND: Manganese, an essential micronutrient, is a potential neurotoxicant in prolonged overexposure. Parkinson-like syndrome, motor deficit, disturbed psychomotor development are typical signs of neuropathological alterations due to Mn in humans. METHODS: Young adult rats, in three groups of 16 each, received 15 and 59 mg/kg b.w. MnCl(2), (control: distilled water) via gavage for 10 weeks, and were kept for further 12 weeks. Correlation of MnCl(2) exposure to body and organ weights, neurobehavioral effects (spatial memory, exploratory activity, psychomotor performance, pre-pulse inhibition), and histopathological changes (gliosis) was sought. RESULTS: By the end of treatment, Mn accumulated in blood, cortex, hippocampus, and parenchymal tissues. Body and organ weights were reduced in high dose rats. All treated rats showed hypoactivity, decreased memory performance, and diminished sensorimotor reaction. In the dentate gyrus of these, GFAP immunoreactivity increased. During the post-treatment period, body weight of the high dose group remained decreased, locomotor activity returned to control, but the lasting effect of MnCl(2) could be revealed by amphetamine. CONCLUSION: Using complex methodology, new data were obtained regarding the relationship between the long-term effects of MnCl(2) at neuronal and behavioral level.

Beta-amyloid pathology in the entorhinal cortex of rats induces memory deficits: implications for Alzheimer's disease.

Alzheimer's disease is characterized by the presence of senile plaques in the brain, composed mainly of aggregated amyloid-beta peptide (Abeta), which plays a central role in the pathogenesis of Alzheimer's disease and is a potential target for therapeutic intervention. Amyloid plaques occur in an increasing number of brain structures during the progression of the disease, with a heavy load in regions of the temporal cortex in the early phases. Here, we investigated the cognitive deficits specifically associated with amyloid pathology in the entorhinal cortex. The amyloid peptide Abeta(1-42) was injected bilaterally into the entorhinal cortex of rats and behavioral performance was assessed between 10 and 17 days after injection. We found that parameters of motor behavior in an open-field as well as spatial working memory tested in an alternation task were normal. In contrast, compared with naive rats or control rats injected with saline, rats injected with Abeta(1-42) showed impaired recognition memory in an object recognition task and delayed acquisition in a spatial reference memory task in a water-maze, despite improved performance with training in this task and normal spatial memory in a probe test given 24 h after training. This profile of behavioral deficits after injection of Abeta(1-42) into the entorhinal cortex was similar to that observed in another group of rats injected with the excitotoxic drug, N-methyl-d-aspartate. Immunohistochemical analysis after behavioral testing revealed that Abeta(1-42) injection induced a reactive astroglial response and plaque-like deposits in the entorhinal cortex. These results show that experimentally-induced amyloid pathology in the entorhinal cortex induces selective cognitive deficits, resembling those observed in early phases of Alzheimer's disease. Therefore, injection of protofibrillar-fibrillar Abeta(1-42) into the entorhinal cortex constitutes a promising animal model for investigating selective aspects of Alzheimer's disease and for screening drug candidates designed against Abeta pathology.

Synaptic remodeling induced by gonadal hormones: neuronal plasticity as a mediator of neuroendocrine and behavioral responses to steroids.

During recent decades, it has become a generally accepted view that structural neuroplasticity is remarkably involved in the functional adaptation of the CNS. Thus, cellular morphology in the brain is in continuous transition throughout the life span, as a response to environmental stimuli. The effects of the environment on neuroplasticity are mediated by, to some extent, the changing levels of circulating gonadal steroid hormones. Today, it is clear that the function of gonadal steroids in the brain extends beyond simply regulating reproductive and/or neuroendocrine events. In addition, or even more importantly, gonadal steroids participate in the shaping of the developing brain, while their actions during adult life are implicated in higher brain functions such as cognition, mood and memory. A large body of evidence indicates that gonadal steroid-induced functional changes are accompanied by alterations in neuron and synapse numbers, as well as in dendritic and synaptic morphology. These structural modifications are believed to serve as a morphological basis for changes in behavior and cellular activity. Due to their growing functional and clinical significance, the specificity, timeframe, as well as the molecular and cellular mechanisms of hormone-induced neuroplasticity have become the focus of many studies. In this review, we briefly summarize current knowledge and the most significant recent discoveries from our laboratories on estrogen- and dehydroepiandrosterone-induced synaptic remodeling in the hypothalamus and hippocampus, two important brain areas heavily involved in autonomic and cognitive operations, respectively.

17beta-Estradiol increases, aging decreases, c-Fos expression in the rat accessory olfactory bulb.

In the present paper we investigated the c-Fos immunoreactivity in the accessory olfactory bulb (AOB) of juvenile, adult and old rats of both sexes, as well as the effect of 17beta-estradiol on the expression of this immediate early gene. Basal c-Fos expression in the olfactory bulb decreased with age, and estrogen treatment caused an increase in the number of neurons expressing c-Fos in the AOB. The results indicate that both aging and estrogen have roles in the ability of neurons to co-ordinate genetic activity. Our observations may explain the decrease in age-related changes of brain plasticity, and provide data for the understanding of hormonally regulated neuronal plasticity.