科研之友
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摘要
Brain nicotinic acetylcholine receptors are involved in several neuropsychiatric disorders, e.g. Alzheimer's and Parkinson's diseases, Tourette's syndrome, schizophrenia, depression, autism, attention deficit hyperactivity disorder, and anxiety. Currently, approaches selectively targeting the activation of specific nicotinic acetylcholine receptors are in clinical development for treatment of memory impairment of Alzheimer's disease patients. These are alpha 4 beta 2 and alpha 7 nicotinic acetylcholine receptor agonists which are believed to enhance cholinergic and glutamatergic neurotransmission, respectively. In order to gain a better insight into the mechanistic role of these two nicotinic acetylcholine receptors in learning and memory, we investigated the effects of the alpha 4 beta 2 nicotinic acetylcholine receptor agonist TC-1827 and the alpha 7 nicotinic acetylcholine receptor partial agonist SSR180711 on hippocampal long-term potentiation (LIP), a widely accepted cellular experimental model of memory formation. Generally, LTP is distinguished in an early and a late form, the former being protein-synthesis independent and the latter being protein-synthesis dependent. TC-1827 was found to increase early LTP in a bell-shaped dose dependent manner, but did not affect late LP. In contrast, the alpha 7 nicotinic acetylcholine receptor partial agonist SSR180711 showed enhancing effects on both early and late LTP in a bell-shaped manner. Furthermore, SSR180711 not only increased early LW, but also transformed it into late LTP, which was not observed with the alpha 4 beta 2 nicotinic acetylcholine receptor agonist Therefore, based on these findings alpha 7 nicotinic acetylcholine receptor (partial) agonists appear to exhibit stronger efficacy on memory improvement than alpha 4 beta 2 nicotinic acetylcholine receptor agonists.
- 出版日期2011-12-5
