Abstract:

The hypothalamic release of glutamate and GABA regulates neurosecretory functions that may control the onset of puberty. This release may be influenced by neurosteroids such as allopregnanolone. Using superfusion experiments we examined the role of allopregnanolone on the K+-evoked and basal [3H]-glutamate and [3H]-GABA release from mediobasal hypothalamus and anterior preoptic area in prepubertal, vaginal opening and pubertal (P) rats and evaluated its modulatory effect on GABAA and NMDA (N-methyl-d-aspartic acid) receptors. Also, we examined the hypothalamic activity and mRNA expression of 3α-hydroxysteroid oxidoreductase (3α-HSOR) – enzyme that synthesizes allopregnanolone – using a spectrophotometric method and RT-PCR, respectively. Allopregnanolone increased both the K+-evoked [3H]-glutamate and [3H]-GABA release in P rats, being the former effect mediated by the modulation of NMDA receptors – as was reverted by Mg2+ and by the NMDA receptor antagonist AP-7 and the latter by the modulation of NMDA and GABAA receptors – as was reverted by Mg2+ and the GABAA receptor antagonist bicuculline. The neurosteroid also increased the basal release of [3H]-glutamate in VO rats in an effect that was dependent on the modulation of NMDA receptors as was reverted by Mg2+. On the other hand we show that allopregnanolone reduced the basal release of [3H]-GABA in P rats although we cannot elucidate the precise mechanism by which the neurosteroid exerted this latter effect. The enzymatic activity and the mRNA expression of 3α-HSOR were both increased in P rats regarding the other two studied stages of sexual development. These results suggest an important physiological function of allopregnanolone in the hypothalamus of the P rat where it might be involved in the ‘fine tuning’ of neurosecretory functions related to the biology of reproduction of the female rats.

Author affiliation: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina

Author affiliation: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina

Author affiliation: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina

Author affiliation: Bazzocchini, V.. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas- Area de Farmacologia; Argentina

Author affiliation: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina

Abstract:

In this work we investigated how the neurosteroid allopregnanolone can modulate learning and memory processes. For this purpose, we used ovariectomized (OVX) rats subcutaneously injected with oestradiol benzoate (E) alone or E and progesterone (P). Then, rats were injected in dorsal hippocampus with allopregnanolone or vehicle. Animals were tested in inhibitory avoidance task (IA task). After behavioural test hippocampal mRNA expression and enzymatic activity of 3-HOR, the enzyme responsible of allopregnanolone synthesis, were analysed. In IA task OVX-EP rats spent less time on platform, compared to those OVX or OVX-E. Regression analyses revealed that there was a significant negative relationship between E-P infusion and performance in this task. Pre-training allopregnanolone administration to OVX-EP rats increased the time spent on the platform. Interestingly, when enzymatic activity of 3-HOR was tested, OVX-EP rats showed a significant decrease in the enzymatic activity, compared with OVX and OVX-E rats. In addition, OVX-EP group showed a significant increase in the enzymatic activity after intrahippocampal infusion of allopregnanolone. On the other hand, when mRNA expression of 3-HOR was analysed no differences were observed when the hippocampal allopregnanolone injection was done. These results suggest that E and P have amnesic effects on female rats, being reversed by allopregnanolone through its modulation on hippocampal 3-HOR activity.

Author affiliation: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Author affiliation: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Author affiliation: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Author affiliation: Bazzocchini, Vanesa Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Author affiliation: García, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Yunes, Roberto Miguel Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Abstract:

In previous studies we have found that blockade of NMDA (N-Methyl-d-Aspartic-Acid)-type glutamatergic receptor with intracerebroventricular (ICV) selective drugs induces an inhibition of lordosis in ovariectomized (OVX) estrogen primed rats receiving progesterone or luteinizing hormone releasing hormone (LHRH). By the opposite way, stimulation with NMDA in OVX estrogen primed rats induced a significant increase of lordosis. In the present study the action of an α1-noradrenergic antagonist, HEAT (BE 2254/2-beta-4-Hydroxyphenyl-Ethyl-Aminomethyl-1-Tetralone), and Metoprolol, a β-noradrenergic antagonist, were studied injecting them ICV previously to NMDA administration in treated OVX estrogen primed rats. In experiment 1, the enhancing effect on lordosis induced by NMDA at high dose (1 μg) was abolished by HEAT administration (P < 0.001 for 3 and 6 μg), and the LH plasma levels were decreased only with the higher dose (P < 0.05), suggesting that behavioral effects are quite more sensitive to the α-blockade than hormonal effects. In experiment 2, enhancing effects on lordosis behavior were not observed with neither the NMDA at low dose (0.5 μg) nor the metoprolol alone (5.71 μg), but a synergism was observed when both were simultaneously administered (P < 0.001). The LH plasma levels were increased by Metoprolol alone (P < 0.05), and powered by the combination with NMDA at low dose (P < 0.01 vs. SAL and NMDA alone); no differences were observed with Metoprolol. LH increase was observed with Metoprolol even without behavioural modifications. These findings strongly suggest that facilitatory and inhibitory effects of NMDA in this model are mediated by α- and β-adrenergic transmission in both, behavioral and hormonal effects.

Author affiliation: Landa, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Gargiulo, Ángel José Martín. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Gargiulo, Mercedes María Lucrecia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina

Author affiliation: Lafuente Sánchez, José Vicente. Universidad del País Vasco; España

Author affiliation: Gargiulo, Pascual Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Abstract:

The reagent MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole) is reduced to formazan in living cells, giving a purple colored product. The product absorbance issusceptible to be measured at a certain wavelength by a spectrophotometer. We report in this paper the use of MTT as a suitable method for checking both the viability of neural tissues as well as the correct location of stereotaxically placed cerebral cannulae. Evidence is given that this method can be useful not only because it is a new way of utilizing a vital staining to evaluate cannulae location, but also because MTT is a simple, effective and cheaper way of assessing the arousal level of neural tissues under study. In doing so, we can effectively test the stimulatory and/or inhibitory actions of several reagents in what we finally named as MTT-micro assay on living tissues: the MTT-malt.

Author affiliation: García, S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Nanfaro, F.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Abstract:

Reproduction is an event that requires the coordination of peripheral organs with the nervous system to ensure that the internal and external environments are optimal for successful procreation of the species. This is accomplished by the hypothalamic-pituitary-gonadal axis that coordinates reproductive behavior with ovulation. The primary signal from the central nervous system is gonadotropin-releasing hormone (GnRH), which modulates the activity of anterior pituitary gonadotropes regulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) release. As ovarian follicles develop they release estradiol, which negatively regulates further release of GnRH and FSH. As estradiol concentrations peak they trigger the surge release of GnRH, which leads to LH release inducing ovulation. Release of GnRH within the central nervous system helps modulate reproductive behaviors providing a node at which control of reproduction is regulated. To address these issues, this review focuses on several critical questions. How is the HPG axis regulated in species with different reproductive strategies? What internal and external conditions modulate the synthesis and release of GnRH? How does GnRH modulate reproductive behavior within the hypothalamus? How does disease shift the activity of the HPG axis.

Author affiliation: Christensen, A.. University of California at Los Angeles; Estados Unidos

Author affiliation: Bentley, G. E.. University of California at Berkeley; Estados Unidos

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Litoral; Argentina

Author affiliation: Perfito, N.. University of California at Berkeley; Estados Unidos

Author affiliation: Wu, T. J.. Uniformed Services University Of The Health Sciences; Estados Unidos

Author affiliation: Micevych, P.. University of California at Los Angeles; Estados Unidos

Abstract:

El núcleo septal lateral forma parte de estructuras subcorticales del cerebro.  La destrucción de dicho núcleo  genera lo que se conoce como síndrome de furia septal. En este trabajo demostramos que el agonista GABAérgico muscimol, en dosis no sedativas, indujo una inhibición del miedo en ratas macho de la cepa Sprague-Dawley, asociada a un aumento de respuestas agresivas a objetos habitualmente neutros. Estos resultados, sumados al hecho de que el núcleo septal lateral participa en diversas entidades psiquiátricas, hace que sea interesante aportar al conocimiento de su función apelando a moduladores que se sabe están presentes en el en dicha estructura del sistema nervioso central.

Destruction of lateral septum –a nucleus located in subcortical regions of the anterior brain– has been related to an entity known as rage septal syndrome. In the present paper we demonstrate that the direct GABAergic agonist muscimol produces “fear inhibition” when tested at non-sedative doses in Sprague-Dawley male rats. This phenomenon is also supported by an increase of aggressive behaviors directed to otherwise neutral objects. Since the septal lateral has been involved in several psychiatric diseases, it appears as potentially interesting to contribute to the knowledge of its function by taking advantage of eventual modulators known to be present in the nucleus.

Author affiliation: Nanfaro, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Bazzocchini, Vanesa Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Universidad de Mendoza; Argentina

Author affiliation: Vega, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Casas, Sebastián Marcelo. Universidad de Mendoza; Argentina

Author affiliation: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Author affiliation: Yunes, Roberto Miguel Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Abstract:

When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side-chain cleavage, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase, cytochrome P450arom, steroid 5α-reductase and 3α-hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.

Author affiliation: Rossetti, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina

Author affiliation: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina

Author affiliation: Holschbach, A.. State University of Colorado - Fort Collins; Estados Unidos

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Abstract:

We have previously observed that intracerebroventricular allopregnanolone (ALLO) injection produced an anxiolytic effect and inhibited sexual receptivity when the test was performed in a separate manner. Also, ALLO reverts learning deficit in female rats in the hippocampi. To study the behavioral effects of an acute treatment with ALLO in the right lateral ventricle we used two approaches: a- A battery test to analyze the anxiety and mating behavior. And b- The avoidance test and novel object recognition test to evaluate its effect on memory and learning. Ovariectomized rats were injected with estrogen and progesterone. After it ALLO or vehicle were administered into the right lateral ventricle. To reach the objective (a) rats were put in a sequential battery test in the next order: 1-Open field. 2- Plus maze task. 3- Mating behavior. For the aim (b) it was performed a Novel Object Recognition Test and Step-down Inhibitory Avoidance Task. ALLO did not affect locomotors-exploratory behavior. Animals treated with ALLO, spent more time and had more entries into the open arm in a plus maze task and lordosis quotient was lower than in the control group. ALLO increased the latency in step down test and had no effects on discrimination index test in NORT. Here we demonstrated that one pharmacological dose of ALLO in ovariectomized primed rats is enough to generate all changes observed in the battery test. Moreover, the acute treatment with ALLO in lateral ventricle enhanced the memory acquisition in an avoidance task.

Author affiliation: Pelegrina, Laura Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: García Menéndez, Sebastián Marcelo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Abstract:

Hemiparkinsonisminduced by 6-hydroxydopamine (6-OHDA) injected in left corpus striatum is a recognized model of motor deficits in rats. Some reports concerning motor deficits indicate a favorable response to steroid administration in hemiparkinsonian animals. However, there is no much information regarding progesterone administration in relation to cognitive and affective dysfunctions. Here we could confirm earlier reports regarding a mild deficit of memory and a noticeable depressive-like behavior 4 weeks after injecting 6-OHDA. We also present some evidence that progesterone could be ? when administered 7 days after the injection of 6-OHDA ? a possible neuroprotector concerning both motor deficits as well as cognitive ? memory- and depression-like behaviors. The affective deficit was reverted by administering the tricyclic antidepressant imipramine. Since Parkinson´s disease is a conspicuous cause of psycho-organic decline in human beings, it would be important to be able of dealing early with non-motor indicators in order to use prospective neuroprotectors to prevent the progression of the disease

Author affiliation: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina

Author affiliation: García Menéndez, Sebastián Marcelo Manuel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Nanfaro, Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

Author affiliation: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Author affiliation: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina

Abstract:

The hypothalamic release of glutamate and GABA regulates neurosecretory functions that may control the onset of puberty. This release may be influenced by neurosteroids such as allopregnanolone. Using superfusion experiments we examined the role of allopregnanolone on the K+-evoked and basal [3H]-glutamate and [3H]-GABA release from mediobasal hypothalamus and anterior preoptic area in prepubertal, vaginal opening and pubertal (P) rats and evaluated its modulatory effect on GABAA and NMDA (N-methyl-D-aspartic acid) receptors. Also, we examined the hypothalamic activity and mRNA expression of 3ahydroxysteroid oxidoreductase (3a-HSOR) – enzyme that synthesizes allopregnanolone – using a spectrophotometric method and RT-PCR, respectively. Allopregnanolone increased both the K+-evoked [3H]-glutamate and [3H]-GABA release in P rats, being the former effect mediated by the modulation of NMDA receptors – as was reverted by Mg2+ and by the NMDA receptor antagonist AP-7 and the latter by the modulation of NMDA and GABAA receptors – as was reverted by Mg2+ and the GABAA receptor antagonist bicuculline. The neurosteroid also increased the basal release of [3H]-glutamate in VO rats in an effect that was dependent on the modulation of NMDA receptors as was reverted by Mg2+. On the other hand we show that allopregnanolone reduced the basal release of [3H]-GABA in P rats although we cannot elucidate the precise mechanism bywhich the neurosteroid exerted this latter effect. The enzymatic activity and the mRNA expression of 3a-HSOR were both increased in P rats regarding the other two studied stages of sexual development. These results suggest an important physiological function of allopregnanolone in the hypothalamus of the P rat where it might be involved in the ‘fine tuning’ of neurosecretory functions related to the biology of reproduction of the female rats.

Author affiliation: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Author affiliation: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Author affiliation: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Author affiliation: Bazzocchini, Vanesa Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Author affiliation: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina; Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Área de Farmacología; Argentina;

Author affiliation: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Author affiliation: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;