Abstract
The present study explored the efficacy of leptin in protecting against in vivo induction of excitotoxic lesions by the glutamatergic analogue ibotenate injected into the developing mouse brain and against in vitro NMDA-induced cell death in primary neuronal cultures. Ibotenate injected intracerebrally (i.c.) to mice on postnatal day 5 produced transcortical necrosis and white matter cysts. Co-treatment with leptin administered i.c. or i.p. reduced ibotenate-induced cortical lesions and white matter cysts by 50%. In vitro, leptin afforded significant neuroprotection of mouse cortical neurons against NMDA cytotoxicity. The neuroprotective effect of leptin was antagonized both in vivo and in vitro by the Jak2 inhibitor AG490, indicating that it was mediated via the leptin receptor and Jak2 activation. These findings are the first evidence for a role of leptin in neuroprotection.
Original language | English |
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Pages (from-to) | 3947-3951 |
Number of pages | 5 |
Journal | NeuroReport |
Volume | 12 |
Issue number | 18 |
DOIs | |
Publication status | Published - Dec 21 2001 |
Externally published | Yes |
Keywords
- Brain lesion
- Ibotenate
- Leptin
- NMDA
- Neuronal cultures
- Newborn mouse
ASJC Scopus subject areas
- General Neuroscience