Long-term treatment with nicotine suppresses neurotoxicity of, and microglial activation by, thrombin in cortico-striatal slice cultures
| Autor: | Mikako Takagi, Toshiaki Kume, Hiroshi Katsuki, Akinori Akaike, Masatoshi Ohnishi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Nicotine Time Factors alpha7 Nicotinic Acetylcholine Receptor Neurotoxins Stimulation In Vitro Techniques Receptors Nicotinic Neuroprotection chemistry.chemical_compound Internal medicine Parietal Lobe Mecamylamine medicine Animals Rats Wistar Pharmacology Methyllycaconitine business.industry Neurotoxicity Thrombin medicine.disease Rats Neostriatum Endocrinology Nicotinic agonist medicine.anatomical_structure Neuroprotective Agents nervous system chemistry Neuroglia Microglia business medicine.drug |
| Zdroj: | European journal of pharmacology. 602(2-3) |
| ISSN: | 1879-0712 |
| Popis: | The mechanisms of tissue injury associated with intracerebral hemorrhage involve multiple actions of thrombin, a blood-derived coagulation factor, on cells within the brain parenchyma, including activation of microglia as well as direct cytotoxicity on neurons. Based on emerging evidence that stimulation of nicotinic acetylcholine receptors provides neuroprotective effects and also suppresses cytotoxic properties of activated microglia, we investigated the effect of nicotine on thrombin-induced pathological changes in cortico-striatal slice cultures. Long-term (15 days), but not short-term (up to 144 h), treatment with nicotine (3-30 microM) partially prevented thrombin-induced neuron loss in the cortical region and tissue shrinkage in the striatal region. In addition, long-term treatment with nicotine suppressed thrombin-induced increase in microglia in a concentration-dependent manner, which was accompanied by suppression of morphological changes of microglia into their activated form. Methyllycaconitine (an alpha7-selective antagonist) and dihydro-beta-erythroidine (an antagonist specific for beta2-containing receptors), as well as mecamylamine (a non subtype-selective nicotinic receptor antagonist), abrogated the protective effect of nicotine against thrombin-induced striatal shrinkage and the inhibitory effect of nicotine against thrombin-induced increase in activated microglia. Besides adding further evidence that nicotinic receptor stimulation exerts neuroprotective functions, these results reveal a novel mode of action of nicotine on neural tissues that appears after long-term treatment. |
| Databáze: | OpenAIRE |
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