Effects of insulin-like growth factor 1 on synaptic excitability in cultured rat hippocampal neurons.
Insulin-like growth factor 1 (IGF-1) has important functions in the brain, including metabolic, neurotrophic, neuromodulatory and neuroendocrine actions, and it also prevents beta amyloid-induced death of hippocampal neurons. However, its functions in the synaptic excitability remain uncertain. Here we investigated the effects of IGF-1 on synaptic excitability in cultured rat hippocampal neurons using whole-cell patch clamp recordings. Incubation the hippocampal neurons with different concentrations of IGF-1 for 24 h or 30 min significantly increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), but had no effect on the frequency of miniature EPSCs (mEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs). The mean amplitudes, rise, and decay kinetics of sEPSCs, mEPSCs, and sIPSCs were not significantly affected by IGF-1, indicating that IGF-1 increased the probability of neurotransmitter release but did not modulate postsynaptic receptors. The effects of IGF-1 were mediated by mitogen-activated protein kinase (MAPK). IGF-1 activated the ERK1/2 signaling pathway in cultured hippocampal neurons, and the inhibitor PD98059 blocked the enhancement of sEPSCs induced by IGF-1. These results demonstrated the regulatory function of IGF-1 on synaptic excitability in hippocampal neurons and its underlying signaling mechanism.
Xing
Changhong
C
Institute of Cerebrovascular Diseases, Xuan Wu Hospital, Capital Medical University, Beijing, China. xch02@sina.com <xch02@sina.com>
Yin
Yanling
Y
Chang
Rui
R
Gong
Xiaoming
X
He
Xiangping
X
Xie
Zuoping
Z
D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects* / Q000502:physiology*
D005419:Flavonoids; D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one