Acetyl-L-carnitine protects striatal neurons against in vitro ischemia: the role of endogenous acetylcholine
| Autor: | Antonio Pisani, Ilaria Barone, Giorgio Bernardi, Paolo Calabresi, Raffaella Nicolai, Barbara Picconi, Menotti Calvani, Paola Benatti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Scopolamine
Ischemia Cholinergic Agents Wistar Muscarinic Antagonists Biology Pharmacology In Vitro Techniques Diamines Neuroprotection Dose-Response Relationship Cellular and Molecular Neuroscience chemistry.chemical_compound Visual Cortex Parasympatholytics Animals Nootropic Agents Drug Interactions Dose-Response Relationship Drug Rats Hemicholinium 3 Scopolamine Hydrobromide Evoked Potentials Neurons Rats Wistar Acetylcholine Pirenzepine Acetylcarnitine Muscarinic acetylcholine receptor medicine Methoctramine Muscarinic antagonist medicine.disease Choline transporter Mitochondrial respiratory chain Biochemistry chemistry Settore MED/26 - Neurologia Drug medicine.drug |
| Popis: | The neuronal death after ischemia is closely linked to the essential role of mitochondrial metabolism. Inhibition of mitochondrial respiratory chain reduces ATP generation leading to a dysregulation of ion metabolism. Acetyl-L-carnitine (ALC) influences the maintenance of key mitochondrial proteins for maximum energy production and it may play a neuroprotective role in some pathological conditions. In this study we have analyzed ALC-mediated neuroprotection on an in vitro model of brain ischemia. Field potential recordings were obtained from a rat corticostriatal slice preparation. In vitro ischemia (oxygen and glucose deprivation) was delivered by switching to a solution in which glucose was omitted and oxygen was replaced with N2. Ten minutes of in vitro ischemia caused an irreversible loss of the field potential amplitude. Pretreatment with ALC produced a progressive and dose-dependent recovery of the field potential amplitude following in vitro ischemia. The neuroprotective effect of ALC was stereospecific since the pretreatment with two different carnitine-related compounds did not cause neuroprotection. The choline transporter inhibitor hemicholinium-3 blocked the neuroprotective effect of ALC. ALC-mediated neuroprotection was also prevented either by the non-selective muscarinic antagonist scopolamine, or by the putative M2-like receptor antagonist methoctramine. Conversely, the effect of ALC was not altered by the M1-like receptor antagonist pirenzepine. These findings show that ALC exert a neuroprotective action against in vitro ischemia. This neuroprotective effect requires the activity of choline uptake system and the activation of M2 muscarinic receptors. |
| Databáze: | OpenAIRE |
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