Progesterone attenuates several hippocampal abnormalities of the wobbler mouse

MEYER M; GONZALEZ DENISELLE M.C; GARGIULO MONACHELLI GM; LIMA A; ROIG P; GENNOUN R; SCHUMACHER M; AF. DE NICOLA

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012

0953-8194

It is now recognized that progesterone plays a protective role for diseases of the central nervous system. In the Wobbler mouse, a model of motoneuron degeneration, progesterone treatment prevents spinal cord neuropathology and clinical progression of the disease. However, neuropathological and functional abnormalities have also been discovered in the brain of Wobbler mice and patients with amyotrophic lateral sclerosis. The present study examined the hippocampus of control and afflicted Wobbler mice and changes in response to progesterone treatment. Mice received either a single progesterone implant (20 mg for 18 days). We found that hippocampal pathology of the untreated Wobblers involved a decreased expression of brain derived neurotrophic factor (BDNF) mRNA, astrogliosis in the stratum lucidum, stratum radiatum and stratum lacunosum-moleculare, decreased doublecortin+ neuroblasts in the subgranular zone of the dentate gyrus and decreased density of GABA immunoreactive hippocampal interneurons and granule cells of the dentate gyrus. Whereas progesterone did not change the normal parameters of control mice, it attenuated several hippocampal abnormalities in the Wobblers. Thus, progesterone increased hippocampal BDNF mRNA expression, decreased GFAP+ astrogliosis and increased the number of GABAergic interneurons and granule cells. Instead, the number of doublecorting expressing neuroblasts and immature neurons remained impaired in both progesterone-treated and untreated Wobblers. In conclusion, progesterone treatment exerted beneficial effects on some aspects of hippocampal neuropathology, suggesting its neuroprotective role in the brain, in agreement with previous data obtained in the spinal cord of Wobbler mice.