Induction of neuritogenesis in PC12 cells by a pulsed electromagnetic field via MEK-ERK1/2 signaling.

We examined the regulation of neuritogenesis by a pulsed electromagnetic field (PEMF) in rat PC12 pheochromocytoma cells, which can be induced to differentiate into neuron-like cells with elongated neurites by inducers such as nerve growth factor (NGF). Plated PC12 cells were exposed to a single PEMF (central magnetic flux density, 700 mT; frequency, 0.172 Hz) for up to 12 h per day and were then evaluated for extent of neuritogenesis or acetylcholine esterase (AChE) activity. To analyze the mechanism underlying the effect of the PEMF on the cells, its effects on intracellular signaling were examined using the ERK kinase (MEK) inhibitors PD098059 and U0126 (U0124 was used as a negative control for U0126). The number of neurite-bearing PC12 cells and AChE activity increased after PEMF exposure without the addition of other inducers of neuritogenesis. Additionally, PEMF exposure induced sustained activation of ERK1/2 in PC12 cells, but not in NR8383 rat alveolar macrophages. Furthermore, U0126 strongly inhibited PEMF-dependent ERK1/2 activation and neuritogenesis. The PEMF-dependent neuritogenesis was also suppressed by PD098059, but not U0124. These results suggest that PEMF stimulation independently induced neuritogenesis and that activation of MEK-ERK1/2 signaling was induced by a cell-type-dependent mechanism required for PEMF-dependent neuritogenesis in PC12 cells.

Modulation of ultraviolet-induced hyperalgesia and cytokine upregulation by interleukins 10 and 13.

1. Exposure to midrange ultraviolet radiation (UVB) is known to produce skin inflammation similar to sunburn. The aim of this study was to characterize the hyperalgesia and cytokine upregulation induced by UVB and their modulation by antiinflammatory cytokines. 2. Acute exposure of the dorsal skin of mice to UVB (200, 250 and 300 mJ cm(2)) resulted in a dose-dependent decrease in the latencies of the hot plate and tail flick tests, without evident signs of skin lesions. 3. The observed hyperalgesia displayed a biphasic temporal evolution with an acute phase (3 - 6 h) and a late (48 - 96 h) phase. 4. Exposure to UVB (300 mJ cm(2)) elicited significant upregulation of interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha and nerve growth factor (NGF), determined by ELISA in the exposed skin. This upregulation was more important during the acute phase of hyperalgesia. 5. Daily treatment of mice, with i.p. injections of either IL-10 or IL-13 (1.5, 7.5 and 15 ng in 100 microl saline) produced a dose-dependent attenuation of the UVB-induced hyperalgesia. 6. Treatment with the highest doses of either IL-10 or IL-13, produced significant attenuation of the levels of the cytokines and NGF by UVB, with relatively more pronounced effects by IL-13. 7. Acute exposure to moderate amounts of UVB results in a systemic hyperalgesia related to the upregulation of cytokine and NGF levels, since both were prevented by treatment with antiinflammatory cytokines.

Neurotrophic factors and CNS disorders: findings in rodent models of depression and schizophrenia.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are proteins involved in neuronal survival and plasticity of dopaminergic, cholinergic and serotonergic neurons in the central nervous system (CNS). Loss of neurons in specific brain regions has been found in depression and schizophrenia, and this chapter summarizes the findings of altered neurotrophins in animal models of those two disorders under baseline condition and following antidepressive and antipsychotic treatments. In a model of depression (Flinders sensitive line/Flinders resistant line; FSL/FRL rats), increased NGF and BDNF concentrations were found in frontal cortex of female, and in occipital cortex of male 'depressed' FSL compared to FRL control rats. Using the same model, the effects of electroconvulsive stimuli (ECS) and chronic lithium treatment on brain NGF, BDNF and glial cell line-derived neurotrophic factors were investigated. ECS and lithium altered the brain concentrations of neurotrophic factors in the hippocampus, frontal cortex, occipital cortex and striatum. ECS mimic the effects of electroconvulsive therapy (ECT) that is an effective treatment for depression and also schizophrenia. Since NGF and BDNF may also be changed in the CNS of animal models of schizophrenia, we investigated whether treatment with antipsychotic drugs (haloperidol, risperidone, and olanzapine) affects the constitutive levels of NGF and BDNF in the CNS. Both typical and atypical antipsychotic drugs altered the regional brain levels of NGF and BDNF. Other studies also demonstrated that these drugs differentially altered neurotrophin mRNAs. Overall, these studies indicate that alteration of brain level of NGF and BDNF could constitute part of the biochemical alterations induced by antipsychotic drugs.