Cerebral chromogranin A and α GABAAR mRNA expression differences are linked to distinct altered hemodynamic functions of two hypertensive rodent models

Encephalic macro- and microcirculation alterations induced by hypertensive conditions are beginning to associated to "organ damages" which, at the cerebral level appears to account for serious neurodegenerative events. In this work, the application of two different hypertensive experimental models, and namely the spontaneous hypertensive rat (SHR) and the hibernating golden hamster, prove to be a valuable comparative tool for monitoring mRNA expression pattern of gamma aminobutyric acidA receptor (GABAAR) alpha subunits and chromogranin A (CGA), two major cerebral modulators of cardiovascular activities. For this purpose hibernation, which displays hypertensive activities during arousal state and a hypotensive state during torpor prove to be an appropriate natural experimental indicator of circadian-dependent altered hemodynamic conditions. Indeed, qPCR analyses demonstrated consistent mRNA expression patterns of some major GABAAR alpha subunits along with distinct CGA transcript variations in some limbic areas such as hypothalamus (HTH), hippocampus (HIP) and amygdala (AMY) plus in brain stem nuclei such as the solitary tract nucleus (SOL) and pons (Ps). Surprisingly these distinct and overlapping variations appeared to prevalently occur during hypertensive states. In a first case, a very great (p<0.001) up-regulation of alpha 2 subunits and CGA was detected in HTH, Ps and medulla oblongata of SHR and hamsters during torpor state along with greatly (p<0.01) reductions of alpha4 in HTH, cerebellum (Cb) and SOL under these same experimental conditions. As far as the other GABAAR alpha subunit and precisely alpha5 is concerned, this subunit turned out to be greatly and moderately (p<0.05) reduced in HIP and in AMY plus Ps, respectively, in both SHR and hamster during arousal state. Interestingly, even in this case CGA mRNA expression resulted to be also greatly and moderately down-regulated in AMY and HIP, respectively, of SHR while during the arousal of the hamster, aside the reduction of AMY and HIP, the brainstem such as SOL, Cb and medulla oblongata plus HTH supplied consistent increases of transcripts of this neuropeptide. Moreover, the evaluation of such GABAARergic alpha subunits and CGA transcriptional levels seem to be tightly related to neurodegenerative events as shown by amino cupric silver ACS reactions being typical of HIP, AMY and medulla oblongata of both SHR and hamster torpor states. Overall, these results tend to provide new insights regarding GABA-CGA cross-talking mechanisms operating during critical hemodynamic disorders and these may constitute crucial factors responsible for the control of baroreceptor reflexes as well as for the promotion of neuroplastic processes during either the recovery or regenerative state following such cardiovascular disorders. Furthermore, these first results may provide encouraging inputs regarding the probable role of GABAergic-CGA interactions in brain dysfunction deriving from sleeping alterations associated to hemodynamic-cerebral disorders , which may have valuable clinical therapeutic bearings.