Evidence indicates that agonists of neuronal nicotinic receptors (nAChRs), including nicotine, can induce neuroprotective and anti-apoptotic effects in the CNS. To study these mechanisms, the present study focused on nicotine-mediated modulation of the extracellular regulated kinase 1 and 2 (ERK1/2) pathway in cultured spinal cord neurons. Exposure to nicotine (0.1-10 microM) for as short as 1 min markedly upregulated levels of phosphorylated ERK1/2 (pERK1/2) and increased total ERK1/2 activity. Inhibition studies with mecamylamine and alpha-bungarotoxin revealed that these effects were mediated by the alpha7 nicotinic receptor. In addition, pre-exposure to U0126, a specific inhibitor of the ERK1/2 signaling, prevented nicotine-mediated anti-apoptotic effects. To indicate if treatment with nicotine also can activate ERK1/2 in vivo, a moderate spinal cord injury (SCI) was induced in rats using a weight-drop device and nicotine was injected 2 h post-trauma. Consistent with in vitro data, nicotine increased levels of pERK1/2 in this animal model of spinal cord trauma. Results of the present study indicate that the ERK1/2 pathway is involved in anti-apoptotic effects of nicotine in spinal cord neurons and may be involved in therapeutic effects of nicotine in spinal cord trauma.

Imipramine and fluoxetine, by modulating glia activation, may exert anti-inflammatory effects in the CNS. It also seems that microglia cells are important target particularly for imipramine.

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