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Anticonvulsant effects of leptin in epilepsy
Sabrina Diano, Tamas L. Horvath
Sabrina Diano, Tamas L. Horvath
Published December 20, 2007
Citation Information: J Clin Invest. 2008;118(1):26-28. https://doi.org/10.1172/JCI34511.
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Commentary

Anticonvulsant effects of leptin in epilepsy

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Abstract

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.

Authors

Sabrina Diano , Tamas L. Horvath

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Figure 1

Schematic illustration of the anticonvulsant effect of blood-borne leptin on hippocampal principal cells.

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Schematic illustration of the anticonvulsant effect of blood-borne lepti...
(A) Leptin derived from the circulation targets pyramidal cells of the hippocampal formation that are innervated by excitatory (red) and inhibitory (green) synapses. Excitatory synapses are frequently established on dendritic spines of pyramidal cells. (B) The report by Xu et al. (8) in this issue of the JCI shows that intranasal leptin administration in two rodent seizure models has an anticonvulsant effect. The effect of leptin on synaptic transmission in the hippocampus involves leptin binding to its receptor, followed by activation of JAK2/PI3K signaling pathways induced by the long form of the leptic receptor (ObR), which alters both pre- and postsynaptic mechanisms and leads to suppression of glutamate-induced excitatory postsynaptic events mediated by AMPA–type glutamate receptors (AMPAR). This suppressed excitatory neurotransmission explains leptin’s anticonvulsant effects.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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