Distribution of membrane progesterone receptor alpha in the male mouse and rat brain and its regulation after traumatic brain injury

MEFFRE, D; LABOMBARDA, F; DELESPIERRE B; CHASTRE,A; DE NICOLA A; STEIN, D; SCHUMACHER M; GUENNOUN, R

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2013 vol. 231 p. 111 - 124

0306-4522

Progesterone has been shown to exert pleiotropic actions in the brain of both male and females. In particular, after traumatic brain injury (TBI), progesterone has important neuroprotective effects. In addition to intracellular progesterone receptors, membrane receptors of the hormone such as membrane progesterone receptor (mPR) may also be involved in neuroprotection. Three mPR subtypes (mPRa, mPRb, and mPRc) have been described and mPRa is best characterized pharmacologically. In the presentstudy we investigated the distribution, cellular localization and the regulation of mPRa in male mouse and rat  brain. We showed by reverse transcription-PCR that mPRais expressed at similar levels in the male and female mouse brain suggesting that its expression may not be influenced by steroid levels. Treatment of males by estradiol or progesterone did not modify the level of expression of mPRa as shown by Western blot analysis. In situ hybridization and immunohistochemistry analysis showed a wide expressionof mPRa in particular in the olfactory bulb, striatum, cortex, thalamus, hypothalamus, septum, hippocampus and cerebellum. Double immunofluorescence and confocal microscopy analysis showed that mPRa is expressed by neurons but not by oligodendrocytes and astrocytes. In the rat brain, the distribution of mPRa was similar to that observed inmouse brain; and after TBI, mPRa expression was induced in oligodendrocytes, astrocytes and reactive microglia. The wide neuroanatomical distribution of mPRa suggeststhat this receptor may play a role beyond neuroendocrine and reproductive functions. However, in the absence of injury its role might be restricted to neurons. The inductionof mPRa after TBI in microglia, astrocytes and oligodendrocytes, points to a potential role in mediating the modulatory effects of progesterone in inflammation, ion and waterhomeostasis and myelin repair in the injured brain.