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P2‐427: Combined nutrient incubation improves receptor function stimulation over single nutrient incubation in pheochromocytoma cells
Author(s) -
Wilde Martijn C.,
Leenders Inge,
Kuipers Almar A.M.,
Wijk Nick,
Kamphuis Patrick J.,
Broersen Laus M.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1506
Subject(s) - receptor , agonist , cholinergic , muscarinic acetylcholine receptor , nutrient , endocrinology , acetylcholine , incubation , medicine , stimulation , chemistry , biology , biochemistry , organic chemistry
Background: Alzheimer’s disease (AD) is characterized by memory loss as a consequence of reduced neurotransmission. Functional deterioration of neuronal components, especially membrane linked components like receptors, is thought to play a significant role. Indeed, deterioration of the cholinergic system is found already early in AD pathogenesis and involves reduction of acetylcholine levels but also reductions in acetylcholine receptors, in particular muscarinic M1 receptors. Former study has shown that membrane-targeted multi-nutrient intervention could increase agonist binding to muscarinic M1 receptors in rats, indicative for enhanced cholinergic neurotransmission. Methods: The current study set out to detect effects of single nutrient and nutrient combinations on receptor agonist binding in neuronal cells. To this end pheochromocytoma cells were incubated with individual nutrients from specific nutrient classes (PUFA’s, nucleotides, phospholipids, B-vitamins and antioxidants) or combinations of nutrients from different classes for 24 hours. Thereafter, a flex-station was used to measure agonist induced changes in membrane potential. In untreated cells it was shown that agonists induced dose-dependent changes in membrane potential. Sub-optimal doses of agonists were then applied to the supplemented cells. Results: The results show that cells incubated with single nutrients or combinations of 2 showed a minor change in membrane potential (approx. 2% increase compared to control). Cells incubated with combinations of nutrients from 3 classes showed an increase of approximately 20% while combining 4 classes resulted in a roughly 40% increase in membrane potential change. The combination of nutrients from all classes into one supplementation resulted in a 60% increase compared to untreated cells. Conclusions: Together, these results show that incubation with nutrients resulted in greater agonist-induced changes in membrane potential, suggesting stronger receptor stimulation. Moreover, agonistinduced changes in membrane potential were especially enhanced in cells incubated with specific combinations of nutrient classes. These results demonstrate that specific combinations of nutrients can effectively enhance receptor functioning and might offer an effective means to improve neurotransmission.