Glucose and age-related changes in memory
Introduction
Cognitive changes accompany aging in humans and other animals, often taking the form of rapid forgetting [1], [6], [9]. We and other laboratories have examined the role of glucose as a cognitive enhancer in both humans and rats [9], [13], [20], [21]. Particularly germane to this brief review, injections of glucose in aged rodents near the time of training reverse age-related impairments in memory, suggesting that changes in blood and brain glucose responses to training may contribute to age-related impairments in memory.
In young rats, extensive evidence indicates that circulating levels of epinephrine, released from the adrenal medulla, enhance memory and act, at least in part, by increasing blood glucose levels. Resting blood and brain extracellular glucose levels are about the same in old and young adult rats. Compared to young rats, aged rats exhibit an exaggerated increase in epinephrine release from the adrenal medulla during training and/or stress. However, the release of epinephrine during training results in only a minimal increase in blood glucose levels in aged rats. These findings are consistent with the view that the excessive rise in epinephrine in the swim task or after a training footshock may be a futile physiological attempt to increase blood glucose levels in response to stress. Of related importance, injections of epinephrine in aged rats result in severely attenuated release of glucose into blood as compared to young rats. Thus, although aged rats have basal blood glucose levels comparable to those of young rats, blood glucose levels in aged rats are not responsive to training or to epinephrine injection.
In addition to changes in blood glucose levels, glucose levels in the extracellular fluid of the brain vary with training and with age. Aged rats show substantially larger decreases in hippocampus extracellular glucose levels during training which accompany age-related cognitive impairments. In addition, systemic injections of glucose at the time of training blunt the depletion in extracellular brain glucose levels and also reverse the impairment in memory in old rats.
Section snippets
Systemic and direct brain administration of glucose enhance learning and memory
Peripheral injections of epinephrine enhance memory in rodents [10], [16] and in humans [3]. Our investigations of glucose as a modulator of memory processes were prompted by the hypothesis that increases in blood glucose levels acted as an intermediary step between peripheral epinephrine release and central modulation of memory processes. In laboratory animals, peripherally administered glucose enhances memory on a wide variety of tasks [9], [13], [21]. Systemic administration of glucose also
Circulating epinephrine and glucose responses to stress and arousal are uncoupled in aged rats
If age-related changes in modulation of memory contribute to impairments in memory, perhaps epinephrine release, and subsequent increases in blood glucose levels, would be impaired in aged rats. The results of several studies indicate that this was only partially correct: circulating epinephrine responses to training and to training-related stress are markedly increased, not decreased, in aged rats. However, blood glucose responses to training and to training-related stress are severely
Brain extracellular glucose levels in the hippocampus decrease during spontaneous alternation tests, an effect reversed by systemic glucose administration, together with enhanced memory on this task
We measured ECF glucose in the hippocampus and striatum of rats during performance of a hippocampus-dependent spontaneous alternation task [17]. Importantly, this task was chosen as one that involved neither aversive nor appetitive rewards or stimuli, in order to minimize any alteration in ECF glucose subsequent to changes in blood glucose after, for example, stress or food reward. The findings indicate that, in young adult rats, hippocampal ECF glucose levels decrease by as much as 30–40%
Conclusions
Glucose appears to make important contributions to age-related changes in memory. In young rats, increases in blood glucose levels appear to mediate the enhancement of memory by epinephrine. Administration of glucose enhances memory and blunts the depletion of brain glucose seen during memory processing. In contrast, aged F-344 rats do not show increases in blood glucose levels after administration of epinephrine, training or stress. Furthermore, the depletion of brain extracellular glucose
Acknowledgements
Research from the author's laboratory described here was supported by research grants from NIA (AG 07648), NINDS (NS 32914), USDA (00-35200-9059), NIDA (DA 16951) and the Alzheimer's Association.
References (33)
Memory changes with age: neurobiological correlates
- et al.
Blood glucose influences memory and attention in young adults
Neuropsychology
(1994) - et al.
Epinephrine enhancement of human memory consolidation: interaction with arousal at encoding
Neurobiol Learn Mem
(2003) - et al.
Cognitive performance is associated with glucose regulation in healthy elderly persons and can be enhanced with glucose and dietary carbohydrates
Am J Clin Nutr
(2000) - et al.
Age-related changes in plasma catecholamine responses to acute swim stress
Neurobiol Learn Mem
(1995) - et al.
Age-related changes in plasma catecholamine and glucose responses of F-344 rats to footshock as in inhibitory avoidance training
Neurobiol Learn Mem
(1995) - et al.
Role of adrenal stress hormones in forming lasting memories in the brain
Curr Opin Neurobiol
(2002) Glucose improvement of memory: a review
Eur J Pharmacol
(2004)- et al.
Dose-dependent action of glucose on memory processes in women: effect on serial position and recall priority
Cogn Brain Res
(1998) - et al.
Intra-septal infusions of glucose potentiate inhibitory avoidance deficits when co-infused with the GABA agonist muscimol
Brain Res
(1997)
Cognitive effects of insulin in the central nervous system
Neurosci Biobehav Rev
Glucose regulation of memory for reward reduction in young and aged rats
Neurobiol Aging
Intra-septal injections of glucose and glibenclamide attenuate galanin-induced spontaneous alternation performance deficits in the rat
Brain Res
Vagotomy attenuates effects of l-glucose but not d-glucose on spontaneous alternation performance
Physiol Behav
Glucose treatment attenuates spatial learning and memory deficits of aged rats on tests of hippocampal function
Neurobiol Aging
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2016, Ageing Research ReviewsCitation Excerpt :Measures of prefrontal cortex function increase transiently in response to glucose consumption (Kumar et al., 2015). Similarly, in aged rodent models complex cognitive behavioral tasks are rapidly improved post-glucose injection (Gold, 2005). On the other hand, it has been suggested that a chronic excess of glucose consumption can contribute to reduced synaptic plasticity and high levels of inflammation, which may contribute to cognitive deficits (Stefanidis and Watt, 2012).