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Volume 14
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10.3390/biom14040428
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Article

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

by
Ivan J. Esperante
1,
Maria Meyer
1,
Carolina Banzan
1,
Maria Sol Kruse
2,
Analia Lima
1,
Paulina Roig
1,
Rachida Guennoun
3,
Michael Schumacher
3,
Alejandro F. De Nicola
1,4 and
Maria Claudia Gonzalez Deniselle
1,5,*
1
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina
2
Laboratory of Neurobiology, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires 1428, Argentina
3
U1195 INSERM and University Paris Sud: “Neuroprotective, Neuroregenerative and Remyelinating Small Molecules”, 94276 Kremlin-Bicêtre, France
4
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina
5
Departamento de Ciencias Fisiológicas, UA1, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina
*
Author to whom correspondence should be addressed.
Biomolecules 2024, 14(4), 428; https://doi.org/10.3390/biom14040428
Submission received: 6 December 2023 / Revised: 22 March 2024 / Accepted: 25 March 2024 / Published: 1 April 2024
(This article belongs to the Special Issue Role of Neuroactive Steroids in Health and Disease)
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Abstract

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 WRs display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in WRs 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 WRs and WR + T + A, and groups showing the rupture of myelin lamellae. WRs showed increased IBA1+ cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR1 and P2Y12R) 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 WRs 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.
Keywords: myelin; testosterone; androgens; aromatase; anastrozole; ALS; Wobbler mouse myelin; testosterone; androgens; aromatase; anastrozole; ALS; Wobbler mouse

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MDPI and ACS Style

Esperante, I.J.; Meyer, M.; Banzan, C.; Kruse, M.S.; Lima, A.; Roig, P.; Guennoun, R.; Schumacher, M.; De Nicola, A.F.; Gonzalez Deniselle, M.C. Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis. Biomolecules 2024, 14, 428. https://doi.org/10.3390/biom14040428

AMA Style

Esperante IJ, Meyer M, Banzan C, Kruse MS, Lima A, Roig P, Guennoun R, Schumacher M, De Nicola AF, Gonzalez Deniselle MC. Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis. Biomolecules. 2024; 14(4):428. https://doi.org/10.3390/biom14040428

Chicago/Turabian Style

Esperante, Ivan J., Maria Meyer, Carolina Banzan, Maria Sol Kruse, Analia Lima, Paulina Roig, Rachida Guennoun, Michael Schumacher, Alejandro F. De Nicola, and Maria Claudia Gonzalez Deniselle. 2024. "Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis" Biomolecules 14, no. 4: 428. https://doi.org/10.3390/biom14040428

APA Style

Esperante, I. J., Meyer, M., Banzan, C., Kruse, M. S., Lima, A., Roig, P., Guennoun, R., Schumacher, M., De Nicola, A. F., & Gonzalez Deniselle, M. C. (2024). Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis. Biomolecules, 14(4), 428. https://doi.org/10.3390/biom14040428

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