RESUMO
Ovarian steroids modulate the neuronal structure and function during the estrous cycle, contrasting peak effects during the proestrus cycle and low effects during the metestrus cycle. An ovariectomy (OVX) decreases gonadal hormones and tests the effects of substitutive therapies. We studied female rats with a normal estrous cycle and we also studied the effects of systemic progesterone (P4, 4.0 mg/kg) or its reduced metabolite allopregnanolone (ALLO, 4.0 mg/kg, both for 10 days) in females who had had an OVX 16.5 weeks prior to the study (long-term OVX) with the novel object recognition test (NORT) for associative memory. The dendritic shape and spine density in Golgi-impregnated basal dendrites (stratum oriens) of hippocampal pyramidal neurons was also studied. Proestrus females had a better performance than metestrus or OVX females in short-term memory (tested 1 h after the acquisition phase). Proestrus and metestrus females showed better results than OVX females for long-term memory (24 h after the initial phase). Both P4 and ALLO recovered the cognitive impairment induced by long-term OVX. Also, proestrus females had a higher density of dendritic spines than metestrus females, OVX reduced the density of spines when compared to intact females, whereas both P4 and ALLO treatments increased the dendritic spine density, number of dendritic branches along the dendritic length, and branching order compared to vehicle. These data add the dendrites of the stratum oriens as an additional site for naturally occurring changes in spine density during the estrous cycle and evidence the actions of progestins in both behavioral recovery and the structural dendritic rearrangement of hippocampal pyramidal neurons in long-term OVX female rats.
Assuntos
Região CA1 Hipocampal , Região CA2 Hipocampal , Disfunção Cognitiva , Espinhas Dendríticas , Ciclo Estral/metabolismo , Aprendizagem , Ovariectomia/efeitos adversos , Pregnanolona/metabolismo , Pregnanolona/farmacologia , Progesterona/metabolismo , Progesterona/farmacologia , Células Piramidais , Animais , Aprendizagem por Associação/efeitos dos fármacos , Aprendizagem por Associação/fisiologia , Comportamento Animal/fisiologia , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA2 Hipocampal/citologia , Região CA2 Hipocampal/efeitos dos fármacos , Região CA2 Hipocampal/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Espinhas Dendríticas/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Longo Prazo/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Pregnanolona/administração & dosagem , Progesterona/administração & dosagem , Células Piramidais/citologia , Células Piramidais/efeitos dos fármacos , Ratos Wistar , Reconhecimento Psicológico/fisiologiaRESUMO
Proechimys (Rodentia: Echimyidae) is a neotropical rodent of the Amazon region that has been successfully colonized in the laboratory and used for experimental medicine. Preliminary studies indicated that Proechimys (casiragua) rodents express an atypical resistance to developing a chronic epileptic condition in common models of temporal lobe epilepsy. Moreover, previous investigation of our laboratory described a remarkably different Proechimy's cytoarchitecture organization of the hippocampal CA2 subfield. In the present study, we investigated the intrinsic neuronal properties and morphological characteristics of the Proechimys's hippocampal pyramidal neurons of the CA1 and CA2 areas. A comparative approach was performed using neurons recorded in Wistar rats. A striking finding in Proechimys rodents was the presence of large pyramidal-like neurons throughout the stratum oriens from CA2 to CA1 area. In order to confirm such distinctive feature of the Proechimys's hippocampus, we performed Nissl staining and immunohistochemistry for neurofilament protein SM311. CA2 pyramidal neurons in the stratum pyramidale of Proechimys exhibited a significantly higher input resistance and lower time constant when compared to corresponding cell groups in the same area of the Wistar rat's. This newly identified population of pyramidal-shaped neurons in stratum oriens of Proechimys exhibited distinct electrophysiological and morphological properties. This included larger capacitance, lower input resistance, larger rheobase, long latency to first action potential and slower firing frequency. In addition, the apical dendrites of these neurons were oriented in parallel to apical dendrites of regular pyramidal neurons in stratum pyramidale. Moreover, these neurons were immunoreactive to SM311 as the majority of the neurons of the pyramidal layer. The functional role of these hippocampal neurons of the rodent Proechimys deserves further investigation.
Assuntos
Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiologia , Região CA2 Hipocampal/citologia , Região CA2 Hipocampal/fisiologia , Células Piramidais/fisiologia , Roedores/fisiologia , Potenciais de Ação/fisiologia , Animais , Eletrofisiologia/métodos , Masculino , Vias Neurais/fisiologia , Vias Neurais/ultraestrutura , Técnicas de Cultura de Órgãos , Células Piramidais/citologia , Ratos , Ratos Wistar , Especificidade da Espécie , Sinapses/fisiologia , Sinapses/ultraestruturaRESUMO
Previous data of our laboratory have shown that the Amazonian rodents Proechimys do not present spontaneous seizures in different models of epilepsy, suggesting endogenous inhibitory mechanisms. Here, we describe a remarkably different Proechimy's cytoarchitecture organization of the hippocampal cornu Ammonis 2 (CA2) subfield. We identified a very distinctive Proechimy's CA2 sector exhibiting disorganized cell presentation of the pyramidal layer and atypical dispersion of the pyramidal-like cells to the stratum oriens, strongly contrasting to the densely packed CA2 cells in the Wistar rats. Studies showed that CA2 is the only cornu ammonis (CA) subfield resistant to the extensive pyramidal neural loss in mesial temporal lobe epilepsy (MTLE) associated to hippocampal sclerosis. Thus, in order to investigate this region, we used Nissl and Timm staining, stereological approach to count neurons and immunohistochemistry to neuronal nuclei (NeuN), parvalbumin (PV), calbindin (CB) and calretinin (CR). We did not notice statistically significant differences in the total number of neurons of the CA2 region between Proechimys and Wistar. However, Proechimys rodents presented higher CA2 volume than Wistar rats. Furthermore, no significant difference in the optical density of parvalbumin-immunoreactivity was found between subject groups. On the other hand, Proechimys presented significant higher density of calbindin and calretinin-immunoreactivity when compared to Wistar rats. In this context, this unique CA2 subfield seen in Proechimys opens up a new set of possibilities to explore the contribution of CA2 neurons in normal and pathological brain circuits.