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Aim: Parkinson's disease (PD) is a progressive neurodegenerative disease that manifests itself clinically after reaching an advanced pathological stage. Besides motor signals, PD patients present cardiovascular and autonomic alterations.Recent data showed that rats induced to Parkinsonism by 6-hydroxydopamine (6-OHDA) administration in the substantia nigra pars compacta (SNpc) showed lower mean arterial pressure (MAP) and heart rate (HR), as reduction in sympathetic modulation. The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic and cardiovascular control, and amino acid neurotransmission has a central role. We evaluate PVN amino acid neurotransmission in cardiovascular and autonomic effects of 6-OHDA Parkinsonism. Methods: Male Wistar rats were submitted to guide cannulas implantation into the PVN. 6-OHDA or sterile saline (sham) was administered bilaterally in the SNpc. After 7 days, cardiovascular recordings in conscious state was performed. Results: Bicuculline promoted an increase in MAP and HR in sham group and exacerbated those effects in 6-OHDA group. NBQX (non-NMDA inhibitor) did not promote changes in sham as in 6-OHDA group. On the other hand, PVN microinjection of LY235959 (NMDA inhibitor) in sham group did not induced cardiovascular alterations, but decreased MAP and HR in 6-OHDA group. Compared to Sham group, 6-OHDA lesion increased the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurons in the PVN and, nNOS inhibition promoted higher increases in MAP and HR. Conclusion: Our data suggest that the decreased baseline blood pressure and heart rate in animals with Parkinsonism may be due to an increased GABAergic tone via nNOS in the PVN. K E Y W O R D Sarterial pressure, baroreflex, bicuculline, heart rate, heart rate variability, nitric oxide

Vasoactive intestinal peptide (VIP) is a neurotransmitter with anorectic effect that acts in the hypothalamus to regulate food intake. Oxytocin is a neuropeptide produced in the hypothalamus that controls energy homeostasis and has an inhibitory role on food intake. Thus, the present study aims at verifying the role of oxytocin as a mediator of VIP on energy homeostasis. For this purpose, intracerebroventricular microinjection of oxytocin receptor antagonist (vasotocin, OVT) or vehicle (NaCl 0.9%) was carried out in male rats, and after 15 min, VIP or saline was microinjected. After 15 min of the second microinjection, food intake was evaluated or euthanasia was undertaken for blood collection. There was a reduction on food intake after VIP microinjection and the pretreatment with OVT partially reversed this effect. Hyperglycemia was observed after VIP microinjection, and pretreatment with OVT partially blocked this effect. Plasma corticosterone concentration was significantly increased after VIP or OVT. Plasma levels of free fatty acids were decreased by VIP, but not when VIP was microinjected after OVT. Thus, OVT partially reversed VIP-induced hypophagia and changes on plasma metabolic parameters, suggesting a role for oxytocin as a mediator of VIP effects on energy homeostasis.

The important involvement of the suprachiasmatic nucleus (SCN) and the activity of vasopressinergic neurons in maintaining the rhythmicity of the female reproductive system depends on the mRNA transcription-translation feedback loops. Therefore, circadian clock function, like most physiological processes, is involved in the events that determine reproductive aging. This study describes the change of mRNA expression of clock genes, Per2, Bmal1, and Rev-erbα, in the hypothalamus-pituitary-gonadal axis (HPG) of female rats with regular cycle (RC) and irregular cycle (IC), and the vasopressinergic neurons activity in the SCN and kisspeptin neurons in the arcuate nucleus (ARC) of these animals. Results for gonadotropins and the cFos/AVP-ir neurons in the SCN of IC were higher, but kisspeptin-ir was minor. Change in the temporal synchrony of the clock system in the HPG axis, during the period prior to the cessation of ovulatory cycles, was identified. The analysis of mRNA for Per2, Bmal1, and Rev-erbα in the reproductive axis of adult female rodents shows that the regularity of the estrous cycle is guaranteed by alternation in the amount of expression of Bmal1 and Per2, and Rev-erbα and Bmal1 between light and dark phases, which ceases to occur and contributes to determining reproductive senescence. These results showed that the desynchronization between the central and peripheral circadian clocks contributes to the irregularity of reproductive events. We suggest that the feedback loops of clock genes on the HPG axis modulate the spontaneous transition from regular to irregular cycle and to acyclicity in female rodents.

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