Steroid profiling in male Wobbler mouse, a model of amyotrophic lateral sclerosis.

GONZÁLEZ DENISELLE, M.C.; LIERE P; PIANOS P; MEYER M; APRAHAMIAN F; CAMBOURG A; DI GIORGIO N; SCHUMACHER M; DE NICOLA AF; GUENNOUN R.

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2016 p. 1 - 16

0013-7227

The Wobbler mouse is used as an animal model for human motoneuron diseases, especially amyotrophic lateral sclerosis (ALS), in the investigation of both pathology and therapeutic treatment. ALS is a fatal neurodegenerative disease, characterized by the selective and progressive death of both upper and lower motoneurons, leading to progressive paralysis. Previous limited experimental and clinical 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. Steroids have indeed been shown to have neuroprotective effects and in some cases neurotoxic effects at sustained high levels. This study was designed to establish a steroid profiling in brain, spinal cord regions, plasma, adrenal glands and testes in two months-old male Wobbler mice and their littermates by means of precise and sensitive gas chromatography coupled to mass spectrometry technology.Here, we demonstrate steroidal changes in male Wobbler mice. The main results are; i) a marked upregulation of corticosterone levels in adrenal glands, plasma, spinal cord regions (cervical, thoracic, lumbar) and brain, ii) a strong decrease in testosterone levels in testis, plasma, spinal cord and brain, and iii) increased levels of progesterone and especially of its reduced metabolites 5-dihydroprogesterone, allopregnanolone and 20-dihydroprogesterone in brain, spinal cord and adrenal glands. Furthermore, Wobbler mice showed a hypothalamic-pituitary-gonadal hypoactivity. Interestingly, plasma concentrations of corticosterone and testosterone correlate well with their respective levels in cervical spinal cord in both control and Wobbler mice.Testosterone downregulation is probably the consequence of adrenal hyperactivity and the upregulation of progesterone and its reduced metabolites may correspond to an endogenous protective mechanism in response to motoneuron degeneration in Wobbler mice. Our findings suggest that increased levels of corticosterone and decreased levels of testosterone in plasma could be a signature of motoneuron degeneration. Thus, plasmatic steroid profiling could be used as a potential disease biomarker and may help in developing therapeutic strategies for motoneuron diseases.