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Distinct α subunit variations of the hypothalamic GABAA receptor triplets (αβγ) are linked to hibernating state in hamsters.

Alò R, Avolio E, Di Vito A, Carelli A, Facciolo RM, Canonaco M - BMC Neurosci (2010)

Bottom Line: At the same time α2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4 expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%).We conclude that different αβγ 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Comparative Neuroanatomy Laboratory, Ecology Department, University of Calabria, Ponte Pietro Bucci, 87030 Arcavacata di Rende, Cosenza, Italy. canonaco@unical.it

ABSTRACT

Background: The structural arrangement of the γ-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 αβγ 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 α subunits considered as shown by a strong (p < 0.01) prevalence of α1 ratio (over total α 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 α2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4 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 (β and γ), elevated β3 and γ3 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 β3 and γ2 during hibernating conditions.

Conclusion: We conclude that different αβγ 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.

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Percentage of α1,2,4,5 mRNA GABAAR expression in hypothalamic areas of NHIB and HIB hamsters. % differences of α1 (a), α2 (b), α4 (c) and α5 (d) expression levels over total α levels in hypothalamic HIB areas were evaluated with respect to their controls and compared to the % differences of NHIB. a,*p < 0.05; b,**p < 0.01; c,***p < 0.001. Arc: arcuate hypothalamic nucleus; MPOA: medial preoptic area; Pe: periventricolar hypothalamic nucleus; Sch: suprachiasmatic nucleus.
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Figure 4: Percentage of α1,2,4,5 mRNA GABAAR expression in hypothalamic areas of NHIB and HIB hamsters. % differences of α1 (a), α2 (b), α4 (c) and α5 (d) expression levels over total α levels in hypothalamic HIB areas were evaluated with respect to their controls and compared to the % differences of NHIB. a,*p < 0.05; b,**p < 0.01; c,***p < 0.001. Arc: arcuate hypothalamic nucleus; MPOA: medial preoptic area; Pe: periventricolar hypothalamic nucleus; Sch: suprachiasmatic nucleus.

Mentions: Surprisingly, however, when the different levels of the single α subunit were reported as a ratio with respect to total α subunit levels considered in the present study, a peculiarly interesting expression pattern was highlighted in these same hypothalamic areas. First of all, the distribution pattern of the different GABAAR subunits (α1,2,4,5) notably differed in the hypothalamic areas of NHIBs as displayed by a very strong (p < 0.001) up-regulation of the α1 subunit (80%) in MPOA during such a physiological state with respect to HIB animals (Figure 4a). Contextually, the other hypothalamic areas of NHIB continued to maintain notably high expression capacities of this specific subunit as shown by very strong and moderately higher (p < 0.05) levels in Arc and Pe, respectively, while very strong levels, instead, characterized Sch of HIBs. On the other hand, elevated α2-expressing neurons seemed to be featured in almost all hypothalamic areas of HIBs as shown by a very strong up-regulated expression pattern in Sch and Arc while only a moderate increase was detected in MPOA (Figure 4b). As far as α4 subunit is concerned, a very strong up-regulation seemed to be mostly featured in Sch of NHIBs whereas a strong increase was reported for Arc of HIBs (Figure 4c). Nonetheless, α5-expressing neurons did not show any evident variations during hibernation with the exception of a somewhat strong up-regulation in MPOA (Figure 4d).


Distinct α subunit variations of the hypothalamic GABAA receptor triplets (αβγ) are linked to hibernating state in hamsters.

Alò R, Avolio E, Di Vito A, Carelli A, Facciolo RM, Canonaco M - BMC Neurosci (2010)

Percentage of α1,2,4,5 mRNA GABAAR expression in hypothalamic areas of NHIB and HIB hamsters. % differences of α1 (a), α2 (b), α4 (c) and α5 (d) expression levels over total α levels in hypothalamic HIB areas were evaluated with respect to their controls and compared to the % differences of NHIB. a,*p < 0.05; b,**p < 0.01; c,***p < 0.001. Arc: arcuate hypothalamic nucleus; MPOA: medial preoptic area; Pe: periventricolar hypothalamic nucleus; Sch: suprachiasmatic nucleus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2944354&req=5

Figure 4: Percentage of α1,2,4,5 mRNA GABAAR expression in hypothalamic areas of NHIB and HIB hamsters. % differences of α1 (a), α2 (b), α4 (c) and α5 (d) expression levels over total α levels in hypothalamic HIB areas were evaluated with respect to their controls and compared to the % differences of NHIB. a,*p < 0.05; b,**p < 0.01; c,***p < 0.001. Arc: arcuate hypothalamic nucleus; MPOA: medial preoptic area; Pe: periventricolar hypothalamic nucleus; Sch: suprachiasmatic nucleus.
Mentions: Surprisingly, however, when the different levels of the single α subunit were reported as a ratio with respect to total α subunit levels considered in the present study, a peculiarly interesting expression pattern was highlighted in these same hypothalamic areas. First of all, the distribution pattern of the different GABAAR subunits (α1,2,4,5) notably differed in the hypothalamic areas of NHIBs as displayed by a very strong (p < 0.001) up-regulation of the α1 subunit (80%) in MPOA during such a physiological state with respect to HIB animals (Figure 4a). Contextually, the other hypothalamic areas of NHIB continued to maintain notably high expression capacities of this specific subunit as shown by very strong and moderately higher (p < 0.05) levels in Arc and Pe, respectively, while very strong levels, instead, characterized Sch of HIBs. On the other hand, elevated α2-expressing neurons seemed to be featured in almost all hypothalamic areas of HIBs as shown by a very strong up-regulated expression pattern in Sch and Arc while only a moderate increase was detected in MPOA (Figure 4b). As far as α4 subunit is concerned, a very strong up-regulation seemed to be mostly featured in Sch of NHIBs whereas a strong increase was reported for Arc of HIBs (Figure 4c). Nonetheless, α5-expressing neurons did not show any evident variations during hibernation with the exception of a somewhat strong up-regulation in MPOA (Figure 4d).

Bottom Line: At the same time α2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4 expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%).We conclude that different αβγ 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Comparative Neuroanatomy Laboratory, Ecology Department, University of Calabria, Ponte Pietro Bucci, 87030 Arcavacata di Rende, Cosenza, Italy. canonaco@unical.it

ABSTRACT

Background: The structural arrangement of the γ-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 αβγ 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 α subunits considered as shown by a strong (p < 0.01) prevalence of α1 ratio (over total α 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 α2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4 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 (β and γ), elevated β3 and γ3 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 β3 and γ2 during hibernating conditions.

Conclusion: We conclude that different αβγ 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.

Show MeSH