Progesterone protective effects in neurodegeneration and neuroinflamation

Abstract

Progesterone is a neuroprotective, promyelinating and antiinflammatory factor for the nervous system. Here we discuss progesterone effects in models of motoneuron degeneration and neuroinflammation. In neurodegeneration of the Wobbler mouse, a subset of spinal cord motoneurons showed increased activity of nitric oxide synthase (NOS), increased intramitochondrial NOS, decreased activity of respiratory chain complexes and decreased activity and protein expression of Mnsuperoxide dismutase type 2 (MnSOD2). Clinically, Wobblers suffered several degrees of motor impairment. Progesterone treatment restored the expression of neuronal markers, decreased the activity of NOS and enhanced complex I respiratory activity and MnSOD2. Long-term treatment with progesterone increased muscle strength, biceps weight and survival. Collectively, these data supported that progesterone prevented neurodegeneration. To study progesterone effects in neuroinflammation, we employed mice with experimental autoimmune encephalomyelitis (EAE). EAE mice spinal cord showed increased mRNA levels of the inflammatory mediators tumour necrosis factor α (TNFα) and its receptor TNFR1, the microglial marker CD11b, iNOS and the toll-like receptor 4 (TLR4). Progesterone pretreatment of EAE mice blocked the proinflammatory mediators, decreased Iba1+ microglial cells and attenuated clinical signs of EAE. Therefore, reactive glial cells became targets of progesterone anti-inflammatory effects. These results open the ground for testing the usefulness of neuroactive steroids for neurological disorders.