Choline-deprivation alters crucial brain enzyme activities in a rat model of diabetic encephalopathy

Abstract

Diabetic encephalopathy describes the moderate cognitive deficits, neurophysiological and structural central nervous system changes associated with untreated diabetes. It involves neurotoxic effects such as the generation of oxidative stress, the enhanced formation of advanced glycation end-products, as well as the disturbance of calcium homeostasis. Due to the direct connection of choline (Ch) with acetylcholine availability and signal transduction, a background of Ch-deficiency might be unfavorable for the pathology and subsequently for the treatment of several metabolic brain diseases, including that of diabetic encephalopathy. The aim of this study was to shed more light on the effects of adult-onset streptozotocin (STZ)-induced diabetes and/or Ch-deprivation on the activities of acetylcholinesterase (AChE) and two important adenosine triphosphatases, namely Na(+),K(+)-ATPase and Mg(2+)-ATPase. Male adult Wistar rats were divided into four main groups, as follows: control (C), diabetic (D), Ch-deprived (CD), and Ch-deprived diabetic (D+CD). Deprivation of Ch was provoked through the administration of Ch-deficient diet. Both the induction of diabetes and the beginning of dietary-mediated provoking of Ch-deprivation occurred at the same day, and rats were killed by decapitation after 30 days (1 month; groups C1, D1, CD1 and D1+CD1) and 60 days (2 months; groups C2, D2, CD2 and D2+CD2, respectively). The adult rat brain AChE activity was found to be significantly increased by both diabetes (+10%, p < 0.001 and +11%, p < 0.01) and Ch-deprivation (+19%, p < 0.001 and +14%, p < 0.001) when compared to the control group by the end of the first (C1) and the second month (C2), respectively. However, the Ch-deprived diabetic rats' brain AChE activity was significantly altered only after a 60-day period of exposure, resulting in a +27% increase (D2+CD2 vs. C2, p < 0.001). Although the only significant change recorded in the brain Na(+),K(+)-ATPase activity after the end of the first month is attributed to Ch-deprivation (+21%, p < 0.05, CD1 vs. C1), all groups of the second month exhibited a statistically significant decrease in brain Na(+),K(+)-ATPase activity (-24%, p < 0.01, D2 vs. C2; -21%, p < 0.01, CD2 vs. C2; -22%, p < 0.01, D2+CD2 vs. C2). As concerns Mg(2+)-ATPase, the enzyme's activity demonstrates no significant changes, with the sole exception of the D2+CD2 group (+21%, p < 0.05, D2+CD2 vs. C2). In addition, statistically significant time-dependent changes concerning the brain Mg(2+)-ATPase activity were recorded within the diabetic (p < 0.05, D2 vs. D1) and the Ch-deprived (p < 0.05, CD2 vs. CD1) rat groups. Our data indicate that Ch-deprivation seems to be an undesirable background for the above-mentioned enzymatic activities under untreated diabetes, in a time-evolving way. Further studies on the issue should focus on a region-specific reevaluation of these crucial enzymes' activities as well as on the possible oxidative mechanisms involved.

Methionine-choline deprivation alters liver and brain acetylcholinesterase activity in C57BL6 mice

“…Having in mind that choline administration leads to increase in brain AChE activity, due to enhancement of its precursor concentration (induction of ACh synthesis) or central muscarinic response (Kilbinger and Kruel 1981), it is expected that choline deprivation would induce decrease in AChE activity. However, similar to our findings, published data indicate an increase in AChE activity, especially during prolonged utilization of choline deficient diet (Bianchi et al 2000;Liapi et al 2008Liapi et al , 2010. Possible explanation for the increase in AChE activity may be related to methionine effect.…”

Brain metabolites in cholinergic and glutamatergic pathways are altered by pancreatic cancer cachexia

“…The relative depletion of choline and choline compounds from cachectic brains indicates compromised brain function, as choline is necessary in several metabolic pathways. [18][19][20] Choline is an essential nutrient 21 utilized for the synthesis of the neurotransmitter acetylcholine (cholinergic activity) and membrane lipids, such as phosphatidylcholine and sphingomyelin that are necessary for cellular integrity and maintenance of efficient mitochondrial oxidative phosphorylation. Choline is also needed for one-carbon (methyl-group) metabolism required for the epigenetic modulation of gene expression/genomic stability and several other methyl-group transfer reactions 22 and is an intracellular messenger (agonist), signalling through brain abundant sigma-1 receptors that are involved in cholinergic transmissions.…”

Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

“…A significant alteration in the activity of rat brain enzymes, such as AChE, Na + /K + -ATPase, and MAO can also provide for measurement of the brain oxidative stress levels induced by STZ [46, 47]. Brain tissue shows a considerable difference in AChE activity in diabetic rat.…”

“…Oxidative stress triggers membrane dysfunction, increasing membrane permeability to ions by inactivating membrane bound enzymes like Na + /K + ATPase, which is very susceptible to free radical attack [51]. Na + /K + ATPase plays an important role in maintaining sodium and potassium gradients and the neuronal electrical functions implicated in neuronal metabolic energy production as well as in the uptake and release of catecholamines [46, 52]. Our results strongly suggest that HP may find a role in reducing the complications of neurotoxicity in DM.…”