Leptin inhibits 4-aminopyridine– and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents
J. Clin. Invest. Lin Xu, et al. 118:272 doi:10.1172/JCI33009 [
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Figure 1Leptin inhibits in vivo focal neocortical seizures in rats induced by 4AP injections into the left motor cortex. (
A) Top trace: 15-minute EEG segment recorded from the frontal area ipsilateral to the injection site 45 minutes after the injection of 12.5 nmol 4AP. Asterisks indicate 4 individual seizures. Bottom trace: a 1-minute seizure at an expanded time base to illustrate the electrographic details of the seizure (underlined). (
B) Top trace: 15-minute EEG segment recorded 45 minutes after the injection of 12.5 nmol 4AP plus 39 pmol leptin shows 2 shorter, lower-amplitude seizures (asterisks). Bottom trace: a 10-second seizure shown at an expanded time base (underlined). Note the different time calibration compared with
A. (
C) Location of the burr hole, injection site, and EEG electrodes relative to standard landmarks. (
D) Leptin reduced the frequency and duration of 4AP-induced seizures. Seizure frequency (left) and duration (right) in rats injected with 12.5 nmol 4AP alone (white bars;
n = 5) or 12.5 nmol plus 39 pmol leptin (black bars;
n = 5). Seizure frequency and duration for each rat were determined from the 60 minutes of EEG recordings collected between 30 and 90 minutes after 4AP injection. *
P < 0.02 for frequency vs. 4AP alone and *
P < 0.001 for duration vs. 4AP alone (unpaired
t test).