Distinct alpha subunit variations of the hypothalamic GABAA receptor triplets (alpha, beta, gamma) are linked to hibernating state in hamsters

Background: The structural arrangement of the gamma-aminobutyric acid type A receptor (GABAAR) is known to be crucial for the maintenance of cerebral-dependent homeostatic mechanisms during the promotion of highly adaptive neurophysiological events of the permissive hibernating rodent, i.e the Syrian golden hamster. In this study, in vitro quantitative autoradiography and in situ hybridization were assessed in major hypothalamic nuclei. Reverse Transcription Reaction-Polymerase chain reaction (RT-PCR) tests were performed for specific GABAAR receptor subunit gene primers synthases of non-hibernating (NHIB) and hibernating (HIB) hamsters. Attempts were made to identify the type of alpha,beta,gamma subunit combinations operating during the switching ON/OFF of neuronal activities in some hypothalamic nuclei of hibernators.Results: Both autoradiography and molecular analysis supplied distinct expression patterns of all alpha subunits considered as shown by a strong (p < 0.01) prevalence of a1 ratio (over total alpha subunits considered in the present study) in the medial preoptic area (MPOA) and arcuate nucleus (Arc) of NHIBs with respect to HIBs. At the same time alpha2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong alpha4 expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%). Regarding the other two subunits (beta and gamma), elevated beta3 and gamma3 mRNAs levels mostly characterized MPOA of HIBs, while prevalently elevated expression concentrations of the same subunits were also typical of Sch, even though this time during the awakening state. In the case of Arc, notably elevated levels were obtained for beta3 and gamma2 during hibernating conditions.Conclusion: We conclude that different alpha,beta,gamma subunits are operating as major elements either at the onset of torpor or during induction of the arousal state in the Syrian golden hamster. The identification of a brain regional distribution pattern of distinct GABAAR subunit combinations may prove to be very useful for highlighting GABAergic mechanisms functioning at least during the different physiological states of hibernators and this may have interesting therapeutic bearings on neurological sleeping disorders.

Background: The structural arrangement of the g-aminobutyric acid type A receptor (GABAAR) is known to becrucial for the maintenance of cerebral-dependent homeostatic mechanisms during the promotion of highlyadaptive neurophysiological events of the permissive hibernating rodent, i.e the Syrian golden hamster. In thisstudy, in vitro quantitative autoradiography and in situ hybridization were assessed in major hypothalamic nuclei.Reverse Transcription Reaction-Polymerase chain reaction (RT-PCR) tests were performed for specific GABAARreceptor subunit gene primers synthases of non-hibernating (NHIB) and hibernating (HIB) hamsters. Attempts weremade to identify the type of abg subunit combinations operating during the switching ON/OFF of neuronalactivities in some hypothalamic nuclei of hibernators.Results: Both autoradiography and molecular analysis supplied distinct expression patterns of all a subunitsconsidered as shown by a strong (p < 0.01) prevalence of a1 ratio (over total a subunits considered in the presentstudy) in the medial preoptic area (MPOA) and arcuate nucleus (Arc) of NHIBs with respect to HIBs. At the sametime a2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong a4expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. thesuprachiasmatic nucleus (Sch; 60%). Regarding the other two subunits (b and g), elevated b3 and g3 mRNAs levelsmostly characterized MPOA of HIBs, while prevalently elevated expression concentrations of the same subunitswere also typical of Sch, even though this time during the awakening state. In the case of Arc, notably elevatedlevels were obtained for b3 and g2 during hibernating conditions.Conclusion: We conclude that different abg subunits are operating as major elements either at the onset oftorpor or during induction of the arousal state in the Syrian golden hamster. The identification of a brain regionaldistribution pattern of distinct GABAAR subunit combinations may prove to be very useful for highlightingGABAergic mechanisms functioning at least during the different physiological states of hibernators and this mayhave interesting therapeutic bearings on neurological sleeping disorders.