Anticonvulsant effects of leptin in epilepsy.
Secreted from adipose tissue at levels proportional to fat stores, the hormone leptin is a critical regulator of the hypothalamic machinery that controls feeding and energy metabolism. Despite the critical role of leptin in the maintenance of energy homeostasis, no leptin-based therapeutic approaches have emerged to combat metabolic disorders such as obesity or diabetes. In this issue of the JCI, Xu et al. report a robust influence of leptin, beyond its role in metabolism, on hippocampal neuronal processes implicated in the etiology of epileptic seizures, learning, and memory (see the related article beginning on page 272). They show, in two rodent seizure models, that leptin administered directly to the brain or nasal epithelium suppresses seizures via direct effects on glutamate neurotransmission in the hippocampus. These observations suggest that leptin may have therapeutic potential in the treatment of epilepsy and strengthen the notion that peripheral metabolic hormones such as leptin play important roles in the regulation of higher brain functions.
Diano
Sabrina
S
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510-8016, USA.
Horvath
Tamas L
TL
D015761:4-Aminopyridine / Q000633:toxicity; D000281:Administration, Intranasal; D000818:Animals; D003292:Convulsants / Q000633:toxicity; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010433:Pentylenetetrazole / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D026902:Potassium Channel Blockers / Q000633:toxicity; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
D015761:4-Aminopyridine; D003292:Convulsants; D053614:Janus Kinase 2; D020738:Leptin; D010433:Pentylenetetrazole; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D018091:Receptors, AMPA; D054411:Receptors, Leptin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat