Anticonvulsant effects of leptin in epilepsy
J. Clin. Invest. Sabrina Diano , et al. 118:26 doi:10.1172/JCI34511 [Go to this article.]

Figure 1
Schematic illustration of the anticonvulsant effect of blood-borne leptin on hippocampal principal cells. (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.