Donepezil improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus.
نویسندگان
چکیده
Insulin-like growth factor-I (IGF-I) exerts beneficial effects on cognitive function. The selective acetylcholinesterase inhibitor donepezil increases serum IGF-I levels in elderly subjects. Because stimulation of sensory neurons induces IGF-I production by releasing calcitonin gene-related peptide (CGRP) in the mouse brain, we hypothesized that donepezil increases IGF-I production by sensory neuron stimulation to improve the cognitive function in mice. Donepezil, but not tacrine, increased the CGRP release from dorsal root ganglion neurons isolated from wild-type (WT) mice. Pretreatment with the protein kinase A inhibitor KT5720 [(9S,10S,12R)-2,3,9,10,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg: 3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzo-diazocine-10-carboxylic acid hexyl ester] reversed the effects induced by donepezil. Increase in tissue levels of CGRP, IGF-I, and IGF-I mRNA in the hippocampus was observed at 4 weeks after oral administration of donepezil in WT mice. In these animals, c-fos expression in spinal dorsal horns, parabrachial nuclei, the solitary tract nucleus, and the hippocampus was increased. Enhancement in angiogenesis and neurogenesis was observed in the dentate gyrus of the hippocampus of WT mice after donepezil administration. Improvement of spatial learning was observed in WT mice after donepezil administration. Oral administration of tacrine for 4 weeks produced none of the aforementioned effects induced by donepezil in WT mice. However, none of the effects observed in WT mice was seen after donepezil administration in CGRP-knockout mice and WT mice subjected to functional denervation. These observations suggest that donepezil may improve cognitive function in mice by increasing the hippocampal production of IGF-I through sensory neuron stimulation. These effects of donepezil may not be dependent on its acetylcholinesterase inhibitory activity.
منابع مشابه
Effects of harmalol on scopolamine-induced memory disorders, anxiety and depression like behaviors in male mice: A behavioral and molecular study
Introduction: Harmalol is a dihydrocarboline compound found naturally in several alcoholic beverages and medicinal plants. This study was designed to investigate the effect of harmalol on memory function and its possible mechanisms in a scopolamine-induced memory disorder model. Materials and Methods: Thirty five male mice were randomly divided into five (n=7) group: Control group )normal sali...
متن کاملBrain-derived neurotrophic factor, insulin-like growth factor-I and its binding protein responses to a session of endurance exercise in healthy elderly men
Purpose: This study investigated the effect of endurance activity on brain-derived neurotrophic factor(BDNF), insulin-like growth factor 1(IGF-1) and its binding protein 3(IGFBP-3) in elderly healthy individuals. Materials and Methods: Eleven healthy old males (mean age of 68 ± 2.31 years old, height of 177 ± 3.1 cm and weight of 79 ± 1.5 kg) were studied. Seventy two hours after maxi...
متن کاملEnhanced Production of Insulin-Like Growth Factor I Protein in Escherichia coli by optimization of five key factors
Abstract Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. The major objective of this study is over- production of recombinant human insulin-like growth factor I( rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. Up to now E. coli expression system has been widely us...
متن کاملEnhanced Production of Insulin-Like Growth Factor I Protein in Escherichia coli by optimization of five key factors
Abstract Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. The major objective of this study is over- production of recombinant human insulin-like growth factor I( rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. Up to now E. coli expression system has been widely us...
متن کاملP84: Effect of Insulin-Like Growth Factor 2 (IGF2) as a Microglia-Derived Anti-Iinflammatory Ccytokine on Improving Memory Impairment Following Hippocampal Intracerebral Hemorrhage in Rat
Insulin-like growth factor 2 (IGF2) as a microglia-derived anti-inflammatory cytokine has a pivotal activity in memory consolidation. However, there is limited evidence on brain cell-originated IGF2 expression, regulation and function in pathological condition and neuro-inflammation. Hence, the present study was conducted to investigate the effect of IGF2 on improving the memory impairment in a...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 330 1 شماره
صفحات -
تاریخ انتشار 2009