Progesterone exerts a neuromodulatory effect on turning behavior of hemiparkinsonian male rats: expression of 3α-hydroxysteroid oxidoreductase and allopregnanollone as suggestive of GABAA receptors involvement

YUNES R.; CASAS S.; GAGLIO E.; CABRERA R.

Parkinson´s Disease

Hindawi Publishing Corporation

Año: 2015

There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegerative diseases. By using a model of hemiparkinsonism in male rats we studied progesterone effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to deal with possible explanatory mechanisms, we studied expression and activity of nigrostriatal 3 alpha-hydroxysteroid-oxido-reductase (3α-HOR), the enzyme responsible for catalyzing progesterone toward allopregnanolone. According to that, we tested a possible neuromodulatory effect of the neuroactive metabolite allopregnanolone on the rotational behavior. Since the aforementioned neurosteroid is a known GABAA modulator, we finally examine the action of the GABAA antagonist bicuculine. We found that progesterone, aside of neuroprotecting our subjects, increased the expression and activity of 3α-HOR in left striatum. It was interesting that allopregnanolone administration in left striatum reversed a clear sign of motor neurodegeneration, i.e. contralateral rotational behavior. GABAA involvement, and its modulation by allopregnanolone, was clearly demonstrated by blocking the effect using bicuculine. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote subchronically neuroprotection, which in turn could be mediated, at least in part, by nongenomic actions of allopregnanolone modulating GABAergic transmission.