Involvement of the dorsal hippocampus muscarinic receptors in the modulation of co...
| Grant number: | 11/19494-8 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | January 01, 2012 |
| Effective date (End): | March 31, 2015 |
| Field of knowledge: | Biological Sciences - Pharmacology |
| Principal Investigator: | Leonardo Resstel Barbosa Moraes |
| Grantee: | Nilson Carlos Ferreira Junior |
| Home Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract The hippocampus is part of limbic system, which can be subdivided in dorsal hippocampus (DH) and ventral hippocampus (VH). The limbic system is involved in the integration of autonomic and emotional responses. It may modulate cardiovascular responses associated with stressful situations. During aversive situation there is blood pressure (BP) increases together with rise of heart rate (HR). This is due, at least in part, to a reduction of baroreflex sensitivity. This reduction is characterized by a reset in the reflex response of HR to higher BP values. The baroreflex is a reflex neural mechanism responsible for maintaining the BP in homeostatic levels. This BP control occurs beat-to-beat through modulation of variables such as HR, systolic volume and peripheral vascular resistance. The neurocircuitry involved with baroreflex modulation include areas of the brain stem such as the nucleus of the solitary tract (NTS), the dorsal and ambiguous vague nucleus, rostral and caudal ventrolateral medulla. However, studies show that forebrain areas such as the bed nucleus of the stria terminalis, the medial prefrontal cortex and DH are also involved with baroreflex activity modulation. The DH neurotransmission inhibition increases the tachycardic and bradycardic reflex responses evoked by intravenous infusion of vasoactive drugs, showing a DH inhibitory influence on baroreflex response. The glutamate (Glu) is a DH neurotransmitter involved with modulation of both autonomic and cardiovascular activity. Glutamatergic terminals and ionotropic receptors were identified within the mice DH. Moreover, administration of Glu into DH was able to evoke cardiovascular responses, suggesting that the glutamatergic system within the DH could modulate the cardiovascular activity. Moreover, the increase in BP and HR evoked by administration of Glu into DH is dependent of the activation of the neuronal isoform of the enzyme that synthesizes nitric oxide (NO), suggesting the existence of an interaction between NMDA receptors and NO within the DH, modulating the cardiovascular system. Finally, it has been shown that Glu release within the DH can be reduced by endocannabinoids through pre-synaptic CB1 receptors activation. However, the role of the DH Glu in the baroreflex modulation has not been studied, as well as the pathway NMDA/NO, and also a possible interaction of the endocannabinoid system with this pathway on baroreflex response. Thus, the proposal this study is to verify the involvement of the glutamatergic neurotransmission, nitrergic and endocannabinoid within the DH on the baroreflex activity modulation. | |