[Gly(14)]-humanin rescues long-term potentiation from amyloid beta protein-induced impairment in the rat hippocampal CA1 region in vivo.
The novel neuroprotective action of Humanin (HN), especially its derivative [Gly(14)]-humanin (HNG), against Alzheimer's disease (AD)-related insults has been reported. However, it is still short of electrophysiological evidence for the protection of HN on synaptic plasticity, and the molecular mechanisms that underlie the neuroprotective function of HN remain largely unknown. The present study examined the effects of intracerebroventricular (i.c.v.) injection of HNG on amyloid beta (Abeta), a main constituent of senile plaques in the AD brain, induced suppression of long-term potentiation (LTP) in the rat hippocampal CA1 region in vivo and investigated the possible mechanism of HNG in LTP protection. We found that application of Abeta fragments 25-35 (Abeta25-35) and 31-35 (Abeta31-35) significantly inhibited high frequency stimulation-induced LTP, while HNG effectively prevented the suppression of LTP induced by Abeta fragments in a dose-dependent manner. After pretreatment with Genistein, a tyrosine kinase inhibitor, the protective action of HNG on LTP was nearly completely abolished. Therefore, the present study demonstrated for the first time that HNG could protect against the neurotoxic Abeta-induced hippocampal LTP impairment and the tyrosine kinase pathway was involved in the neuroprotective action of HNG, suggesting that HNG might be one of the promising candidates for the treatment of AD in the future.
Guo
Fen
F
Department of Neurobiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
Jing
Wei
W
Ma
Cun-Gen
CG
Wu
Mei-Na
MN
Zhang
Jun-Fang
JF
Li
Xin-Yi
XY
Qi
Jin-Shun
JS
D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; C427211:humanin