Axonoprotection by Progesterone in the spinal cord of Experimental Autoimmune Encephalomyelitis (EAE) mice

GARAY LI, GONZÁLEZ DENISELLE MC., LIMA A. ROIG P., DE NICOLA AF

Buenos Aires

Congreso; III Iberoamerican Congress on Neuroimmunomodulation; 2009

EAE and Multiple Sclerosis share neuropathological abnormalities. We have previously shown improved clinical outcome, decreased immune cell infiltration and demyelination of the spinal cord in EAE mice treated with progesterone. Considering the role of axonal degeneration in neurological disabilities, and the neuroprotective effects of progesterone in neurodegeneration and injured spinal cord, this study was intended to elucidate progesterone actions on the EAE axonal pathology. Two groups of animals were studied: progesterone implanted (EAE+PROG) and steroid free mice (EAE). Measures included: a-density of ventral funiculus axons in semithin sections. b-number of amyloid precursor protein (APP)+ spheroids. c-GAP-43 mRNA and protein expression as an indicator of aberrant axonal growth. Progesterone significantly increased axonal density: control: 191.84±4.0, EAE: 108,9±5,4 and EAE+PROG: 152,9±5,9; (p<0.01 vs. EAE). In addition, damaged APP+ axons/mm2 in EAE was 40,84±6,31 and significantly decreased in EAE+PROG: 18,81±2,29 (p<0.004). Finally, the hyperexpression of GAP-43 mRNA in EAE motoneurons vs. control mice was significant attenuated with steroid treatment (Nºgrains/mm2 EAE: 0,0837±0,012 vs. CTRL 0,025±0,003, p<0.05; EAE+PROG: 0,043±0,009; p<0.05 vs. EAE). Conclusion: progesterone contributed to the preservation of axonal density and integrity that, together with its promyelinating effect, could counteract neurotransmission abnormalities developing in EAE.