Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Central Nervous System (CNS)
Neurodegeneration
Sensory system
Motor control
Mood Disorders
Other disorders
Muscular system
Joints
Metabolism
Cross-disciplinary subjects
Preclinical studies and opioids: role in crisis management in the United States Authors
S. Coyral-Castel, L. Tosca, G. Ferreira, E. Jeanpierre, C. Rame et al.
Lab
INRA, UMR6175, Unité de Physiologie de la Reproduction et des Comportements, Nouzilly, France.
Journal
Journal of Neuroendocrinology
Abstract
Hypothalamic AMP-activated kinase (AMPK) is a key regulator of food intake in mammals. Its role in reproduction at the central level and more precisely in GnRH release has never been investigated. We showed that each subunit of AMPK is present in immortalised GnRH neurones (GT1-7 cells). Treatment with 5-aminoimidazole-4-carboxamide-1-_-D-ribonucleoside (AICAR) and metformin, two activators of AMPK, increased dose-dependent and time-dependent phosphorylation of AMPK_ atThr172 in GT1-7 cells. Phosphorylation of acetyl-coenzyme A carboxylase at ser79 also increased. Treatment with AICAR (5 mM) or metformin (5 mM) for 4h inhibited GnRH release in the presence or absence of GnRH (10-8M). Specific AMPK inhibitor compound C completely eliminated the effects of AICAR or metformin on GnRH release. Finally, we determined the central effects of AICAR in vivo on food intake and oestrous cyclicity. Ten-week-old female rats received a 50 _g AICAR or a saline intracerebroventricular (i.c.v.) injection. We detected increased AMPK and ACC phosphorylation, specifically in the hypothalamus, thirty minutes after the AICAR injection. Food intake was significantly higher (p<0.05) in animals treated with AICAR than in animals injected with saline, 24h after injection. This effect was abolished after one week. Moreover, during the four weeks following injection, the interval between two oestrous stages was significantly lower in the AICAR group than in the saline group. Our findings suggest that AMPK activation may act directly at the hypothalamic level to affect fertility by modulating GnRH release and oestrous cyclicity.