| Autor: |
Esperante IJ; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina., Meyer M; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina., Banzan C; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina., Kruse MS; Laboratory of Neurobiology, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina., Lima A; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina., Roig P; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina., Guennoun R; U1195 INSERM and University Paris Sud: 'Neuroprotective, Neuroregenerative and Remyelinating Small Molecules', 94276 Kremlin-Bicêtre, France., Schumacher M; U1195 INSERM and University Paris Sud: 'Neuroprotective, Neuroregenerative and Remyelinating Small Molecules', 94276 Kremlin-Bicêtre, France., De Nicola AF; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina.; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina., Gonzalez Deniselle MC; Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina.; Departamento de Ciencias Fisiológicas, UA1, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina. |
| Abstrakt: |
Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The Wobbler ( WR ) mouse exhibits motoneuron degeneration, gliosis and myelin deterioration in the cervical spinal cord. Since male WR s display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in WR s in the absence or presence of the aromatase inhibitor, anastrozole (A). We studied myelin by using luxol-fast-blue (LFB) staining, semithin sections, electron microscopy and myelin protein expression, density of IBA1 + microglia and mRNA expression of inflammatory factors, and the glutamatergic parameters glutamine synthetase (GS) and the transporter GLT1. Controls and WR + T showed higher LFB, MBP and PLP staining, lower g-ratios and compact myelin than WR s and WR + T + A, and groups showing the rupture of myelin lamellae. WR s showed increased IBA1 + cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR 1 and P 2 Y 12 R) vs. controls or WR + T. IBA1 + cells, and CD11b were not reduced in WR + T + A, but inflammatory factors' mRNA remained low. A reduction of GS + cells and GLT-1 immunoreactivity was observed in WR s and WR + T + A vs. controls and WR + T. Clinically, WR + T but not WR + T + A showed enhanced muscle mass, grip strength and reduced paw abnormalities. Therefore, T effects involve myelin protection, a finding of potential clinical translation. |
