Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 4; p. 428
• Main Authors: Esperante, Ivan J, Meyer, Maria, Banzan, Carolina, Kruse, Maria Sol, Lima, Analia, Roig, Paulina, Guennoun, Rachida, Schumacher, Michael, De Nicola, Alejandro F, Gonzalez Deniselle, Maria Claudia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: ALS; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Anastrozole; Androgens; Animals; Aromatase; CD11b antigen; Demyelination; Disease; Disease Models, Animal; Electron microscopy; Estrogens; Excitatory Amino Acid Transporter 2 - genetics; Excitatory Amino Acid Transporter 2 - metabolism; Gene expression; Gliosis; Glutamate-ammonia ligase; Glutamatergic transmission; Health aspects; Immunoreactivity; Inflammation; Laboratory animals; Lamellae; Male; Males; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Microscopy; Myelin; Myelin proteolipid protein; Myelin Sheath - drug effects; Myelin Sheath - metabolism; Myelination; Nervous system; Neuropathology; Oxidative stress; Physiological aspects; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Testosterone; Testosterone - pharmacology; TLR4 protein; Toll-like receptors; Argentina; United States > US; myelin; Wobbler mouse; androgens; aromatase; testosterone; ALS; anastrozole
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14040428

Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The ( ) mouse exhibits motoneuron degeneration, gliosis and myelin deterioration in the cervical spinal cord. Since male s display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in 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 + T showed higher LFB, MBP and PLP staining, lower g-ratios and compact myelin than s and + T + A, and groups showing the rupture of myelin lamellae. s showed increased IBA1 cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR and P Y R) vs. controls or + T. IBA1 cells, and CD11b were not reduced in + T + A, but inflammatory factors' mRNA remained low. A reduction of GS cells and GLT-1 immunoreactivity was observed in s and + T + A vs. controls and + T. Clinically, + T but not + T + A showed enhanced muscle mass, grip strength and reduced paw abnormalities. Therefore, T effects involve myelin protection, a finding of potential clinical translation.