Brain Excitatory/Inhibitory Circuits Cross-Talking with Chromogranin A During Hypertensive and Hibernating States

G.      Giusi; R.      Alo; E.      Avolio; M.      Zizza; R.      M. Facciolo; G.      Talani; G.      Biggio; E.      Sanna; M.      Canonaco

Abstract

To date, many scientific attempts have been directed towards the development of experimental models for the identification of neuronal mechanisms evoking cardiovascular and hemodynamic dysfunctions. The spontaneously hypertensive rat (SHR), a genetic model of essential hypertension, has become a valuable rodent for the characterization of molecular markers in hypertensive-related diseases. Recently, growing interests have also been directed to a new experimental paradigm i.e. hibernation, a physiological state consenting the hamster (Mesocricetus auratus) to activate protective mechanisms against ischemic-like complications during the arousal phase. With this intention, the present review will focus attention on specific neurosignaling systems involved with the preservation of hemodynamic conditions in those brain areas that play a pivotal role on such a feature. It is widely known that healthy neurons conserve their structural and responsiveness properties in presence of a constant blood supply, which is assured by their coupling to microvessels and perivascular astrocytes as well as by secretory proteins such as chromogranin A (CgA). So, it will be interesting to establish if this protein alone or with the participation of excitatory/inhibitory neurosignals is capable of influencing some brain areas controlling cardiovascular conditions in both SHRs and hibernating hamsters. In this context, the present work will deliver the most important findings regarding neuronal CgA and its cross-talking ability with major inhibitory (GABA/adenosine) and/or excitatory (glutamate) neuroreceptor systems in relation to hypertensive/hypotensive states of both animal models. Indications deriving from such approaches may provide clinically useful insights regarding their role as protective factors of hemodynamic and neurological disorders.

Keywords: Spontaneously hypertensive rats, brain stem, GABA, glutamate, adenosine, hibernation, neuroprotection, synaptic plasticity, granins, neuroinflammation, hypothalamus, cardiovascular functions, hamster.