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Artículo

Steroid profiling in male wobbler mouse, a model of Amyotrophic Lateral Sclerosis

Gonzalez Deniselle, Maria ClaudiaIcon ; Liere, Philippe; Pianos, Antoine; Meyer, Maria; Aprahamian, Fanny; Cambourg, Annie; Di Giorgio, Noelia PaulaIcon ; Schumacher, Michael; de Nicola, Alejandro FedericoIcon ; Guennoun, Rachida
Fecha de publicación: 01/11/2016
Editorial: Endocrine Society
Revista: Endocrinology
ISSN: 0013-7227
e-ISSN: 1945-7170
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular; Neurociencias

Resumen

The Wobbler mouse is an animal model for human motoneuron diseases, especially amyotrophic lateral sclerosis (ALS), used in the investigation of both pathology and therapeutic treatment. ALS is a fatal neurodegenerative disease, characterized by the selective and progressive death of motoneurons, leading to progressive paralysis. Previous limited studies have reported steroidal hormone dysregulation in Wobbler mouse and in ALS patients, suggesting endocrine dysfunctions which may be involved in the pathogenesis of the disease. In this study, we established a steroid profiling in brain, spinal cord, plasma, adrenal glands, and testes in 2-month-old male Wobbler mice and their littermates by gas chromatography coupled to mass spectrometry. Our results show in Wobbler mice the following: 1) a marked up-regulation of corticosterone levels in adrenal glands, plasma, spinal cord regions (cervical, thoracic, lumbar) and brain; 2) a strong decrease in T levels in the testis, plasma, spinal cord, and brain; and 3) increased levels of progesterone and especially of its reduced metabolites 5α-dihydroprogesterone, allopregnanolone, and 20α-dihydroprogesterone in the brain, spinal cord, and adrenal glands. Furthermore, Wobbler mice showed a hypothalamic-pituitary-gonadal hypoactivity. Interestingly, plasma concentrations of corticosterone and T correlate well with their respective levels in cervical spinal cord in both control and Wobbler mice. T down-regulation is probably the consequence of adrenal hyperactivity, and the up-regulation of progesterone and its reduced metabolites may correspond to an endogenous protective mechanism in response to motoneuron degeneration. Our findings suggest that increased levels of corticosterone and decreased levels of T in plasma could be a signature of motoneuron degeneration.
Palabras clave: Steroids , Mice , Amytrophic Lateral Sclerosis , Brain , Corticosterone , Progesterone
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info:eu-repo/semantics/embargoedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/24577
URL: https://academic.oup.com/endo/article-abstract/157/11/4446/2758423/Steroid-Profi
DOI: http://dx.doi.org/10.1210/en.2016-1244
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Gonzalez Deniselle, Maria Claudia; Liere, Philippe; Pianos, Antoine; Meyer, Maria; Aprahamian, Fanny; et al.; Steroid profiling in male wobbler mouse, a model of Amyotrophic Lateral Sclerosis; Endocrine Society; Endocrinology; 157; 11; 1-11-2016; 4446-4460
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