Glucose enhancement of scopolamine-induced increase of hippocampal high-affinity choline uptake in mice: relation to plasma glucose levels

doi:10.1016/0006-8993(95)00415-M

Brain Research

Volume 685, Issues 1–2, 10 July 1995, Pages 99-104

https://doi.org/10.1016/0006-8993(95)00415-M Get rights and content

Abstract

The administration of glucose has been shown to improve memory for various learning tasks in rodents. In humans, glucose also increases declarative memory performance in elderly people and in some patients with mild Alzheimer's disease. One of the possible physiological bases for the effect of glucose on memory processes is a facilitation of cholinergic function through increased synthesis. In support of this hypothesis, glucose was shown to attenuate the amnesia induced by scopolamine and, in similar conditions, glucose increased extracellular levels of acetylcholine following a scopolamine injection. To further examine the interaction between glucose and cholinergic function, the present experiment measured the effects of combined injections of glucose and scopolamine on hippocampal sodium-dependent high-affinity choline uptake, an indirect index of cholinergic activity. Results showed that the injection of 3 g/kg glucose enhanced the increase in high affinity choline uptake in hippocampal synaptosomes produced by scopolamine. A regression analysis revealed the existence of a positive correlation between plasma blood glucose level and hippocampal choline uptake particularly in the animals receiving a combined injection of scopolamine and glucose. These data further support the hypothesis that glucose administration can facilitate acetylcholine synthesis under certain conditions and that this action could explain how glucose attenuates scopolamine-induced amnesia.

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Glucose may modulate the activity of α7 receptors by regulating local extracellular choline levels. Previous studies indicate that glucose regulates high-affinity choline uptake and can act synergistically to improve memory when administered together with choline (Kopf et al., 2001; Micheau et al., 1995; Messier et al., 1990). However, the effects of glucose on extracellular choline levels, in the context of memory enhancement, have not been directly investigated.
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Central administration of angiotensin IV (Ang IV) analogues attenuates scopolamine-induced amnesia. Ang IV mediates its effects by binding to a high affinity, binding site, AT₄ receptor, that has recently been identified as insulin regulated aminopeptidase (IRAP). The purpose of this study was to examine the effect of the distinct AT₄ ligand, LVV-hemorphin-7 (LVV-H7), on scopolamine-induced learning deficits, one which involves fear-conditioning and the other spatial learning. Rats were pretreated with an intracerebroventricular (ICV) dose of scopolamine hydrobromide followed by treatment with 1 nmol LVV-H7 or artificial cerebrospinal fluid (aCSF). During the acquisition phase of the water maze task, daily ICV infusions of 1 nmol of LVV-H7 25 min after scopolamine treatment produced marked improvement in both the latency and distance swum in order to locate the submerged platform using visual cues compared to animals treated with scopolamine only. In addition, the same dose of LVV-H7 attenuated the learning deficit observed for scopolamine-treated animals in the passive avoidance task. These studies clearly demonstrate that LVV-H7, like Ang IV, is a pharmacologically active AT₄ ligand that attenuates the deleterious effects of scopolamine on learning performance in two different behavioral paradigms.
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Metabolism under changing fuel supply is controlled by the glucose-fatty acid cycle. Its evolutionary prototypes were programmed to provide optimal resilience in the feast and famine lifestyle of microorganisms. The counterregulatory processes, activated during nutrient deprivation, include hypometabolism and oxidative stress and aim to preserve glucose for anabolic needs and promote the oxidative utilization of fatty acids and ketone bodies. Conserved from bacteria to man, the program ensures the survival of a deprived organism and controls divergent processes—such as sporulation, hibernation, and starvation. The cycle is controlled by the antagonistic insulin/glucocorticoid couple. The pattern of hormone/neurotransmitter changes in a variety of central nervous system (CNS) ontogenetic and accidental/degenerative events is surprisingly uniform: the desensitization/degeneration of proglucolytic agents and activation of prolipolytic hormones/neurotransmitters paralleled by hypometabolism and downregulation of glucose utilization. Thus, probing various brain pathologies (e.g., stroke, traumatic injury, epilepsy, Alzheimer disease) and ontogenetic events (maturation, aging) for metabolic stress signatures reveals their shared heritage as metabolic deprivation syndromes. Neurotransmitters are the dual conveyors of intercellular communication (enabling affective and cognitive processes) and energy homeostasis, establishing a psychosomatic continuum. In this holistic approach, psychosocial stress, depression, and psychosis can be understood as heterogeneous phenotypes of psychosocial/ metabolic stress pathologies.
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Research reportGlucose enhancement of scopolamine-induced increase of hippocampal high-affinity choline uptake in mice: relation to plasma glucose levels

Abstract

Life Sci.

Pharmacol. Biochem. Behav.

Brain Res.

Behav. Brain Res.

Brain Res.

Biochem. Pharmacol.

Neurobiol. Aging.

Neuropharmacology

Neurobiol. Aging

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Behav. Neur. Biol.

Neurobiol. Aging

Behav. Brain Res.

Behav. Brain Res.

Behav. Neural Biol.

Neurobiol. Aging

Behav. Neural Biol.

Brain Res.

Neurobiol. Aging

Neuropharmacology

Pharmacol. Biochem. Behav.

Brain Res. Bull.

Behav. Neural. Biol.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Brain Res.

Japan. J. Pharmacol.

Brain Res.

Neurosci. Lett.

Glucose attenuates cold-induced impairment of delayed matching-to-sample performance in rats

Psychobiology

Effect of oxotremorine, physostigmine, and scopolamine on brain acetylcholine synthesis -a study using HPLC

Neurochem. Res.

Research report
Glucose enhancement of scopolamine-induced increase of hippocampal high-affinity choline uptake in mice: relation to plasma glucose levels