Effects of dietary choline on memory and brain chemistry in aged mice

doi:10.1016/0197-4580(85)90072-7

Neurobiology of Aging

Volume 6, Issue 1, Spring 1985, Pages 51-56

https://doi.org/10.1016/0197-4580(85)90072-7 Get rights and content

Abstract

The purpose of this study was to investigate in more detail the characteristics of the age-related extension of the retrograde amnesia gradient previously demonstrated in a passive avoidance task [6]. In Experiment 1, it was found that while 2–3 month old mice were susceptible to the amnesic effects of anisomycin (ANI) only when given prior to 15 min post-training, memory of 14–16 month old mice was susceptible to disruption when ANI was given as late as 20 min post-training, and retention of 17–20 month old mice was impaired when ANI was injected even as late as 30 min after training. Experiment 2 examined whether the age-related change in susceptibility to the effects of ANI could be ameliorated by chronic pretreatment with a choline-enriched diet. Results showed that ANI injected 20 min after training did not induce amnesia in choline treated mice (14.5 month old), but did induce amnesia when injected 15 min post training. Subsequent assay of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) activity showed that choline treatment significantly reduced ChAT activity but did not affect TH activity. It appears that dietary choline treatment can render new long-term memories less susceptible to disruption following training.

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Cited by (16)

‘Tagging’ along memories in aging: Synaptic tagging and capture mechanisms in the aged hippocampus
2017, Ageing Research Reviews
Citation Excerpt :
MAPK-mediated signaling shows age-dependent alterations (Zhen et al., 1999) which has been shown for nerve growth factor (NGF) signaling in the septo-hippocampal pathway (Williams et al., 2007; Williams et al., 2006). Some authors have also suggested that the time for transition from short-term to long-term memory is extended in aging, probably due to slowdown in the protein synthesis or transcriptional mechanisms (Essman, 1982; Mizumori et al., 1985). Another protein, that is a mechanistic target of rapamycin complex 2 (mTORC2), controls the actin polymerization required for consolidation of long-term memory (Huang et al., 2013) and the activity of mTORC2 declines with age as demonstrated in fruit flies and rodents (Reviewed by Johnson et al. (2015)).
Aging is accompanied by a general decline in the physiological functions of the body with the deteriorating organ systems. Brain is no exception to this and deficits in cognitive functions are quite common in advanced aging. Though a variety of age-related alterations are observed in the structure and function throughout the brain, certain regions show selective vulnerability. Medial temporal lobe, especially the hippocampus, is one such preferentially vulnerable region and is a crucial structure involved in the learning and long-term memory functions. Hippocampal synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD), are candidate cellular correlates of learning and memory and alterations in these properties have been well documented in aging. A related phenomenon called synaptic tagging and capture (STC) has been proposed as a mechanism for cellular memory consolidation and to account for temporal association of memories. Mounting evidences from behavioral settings suggest that STC could be a physiological phenomenon. In this article, we review the recent data concerning STC and provide a framework for how alterations in STC-related mechanisms could contribute to the age-associated memory impairments. The enormity of impairment in learning and memory functions demands an understanding of age-associated memory deficits at the fundamental level given its impact in the everyday tasks, thereby in the quality of life. Such an understanding is also crucial for designing interventions and preventive measures for successful brain aging.
Metabolic imprinting of choline by its availability during gestation: Implications for memory and attentional processing across the lifespan
2003, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Because Ch neurons are important for both short- and long-term memory processes in a variety of species [8,11], the findings that choline availability modified Ch transmission stimulated research on the behavioral effects of modifying choline intake during adulthood and old age. Although increasing the amount of choline or lecithin can improve performance on certain behavioral tasks in mature subjects [8,9,72,83], attempts to improve memory performance in aged humans or animals have not generally succeeded—for review see Ref. [8,11]. It has been suggested that one reason for this failure in geriatric subjects may be that the aged brain is unable to incorporate extra amounts of choline into acetylcholine, as reportedly occurs in younger brain tissue [9].
A growing body of research supports the view that choline is an essential nutrient during early development that has long-lasting effects on memory and attentional processes throughout the lifespan. This review describes the known effects of alterations in dietary choline availability both in adulthood and during early development. Although modest effects of choline on cognitive processes have been reported when choline is administered to adult animals, we have found that the perinatal period is a critical time for cholinergic organization of brain function. Choline supplementation during this period increases memory capacity and precision of the young adult and appears to prevent age-related memory and attentional decline. Deprivation of choline during early development leads to compromised cognitive function and increased decline with age. We propose that this organizational effect of choline availability may be due to relatively permanent alterations in the functioning of the cholinergic synapse, which we have called ‘metabolic imprinting’.
Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats
2000, Neurotoxicology and Teratology
Prenatal alcohol exposure can disrupt brain development and lead to a myriad of behavioral alterations, including motor coordination deficits, hyperactivity, and learning deficits. There remains a need, however, to identify treatments and interventions for reducing the severity of alcohol-related neurodevelopmental disorders. Some of the alcohol-induced deficits in learning may be related to alterations in cholinergic functioning. Interestingly, there is a growing literature demonstrating that pre- and/or early postnatal choline supplementation can lead to long-term enhancement in learning and memory and cholinergic activity in rats. The present study examined whether such early choline supplementation might counter the effects of prenatal alcohol treatment on a visuospatial discrimination task. Pregnant Sprague–Dawley rats were randomly assigned to one of three prenatal treatment groups. One group received a liquid diet containing 35% ethanol-derived calories (EDC) from gestational day (GD) 6–20. A second group served as a pair-fed (PF) control group and the third group served as an ad lib lab chow (LC) control. On postnatal day (PD) 2, pups were assigned within-litter to one of three postnatal treatments: choline, saline vehicle, or no treatment. Choline and vehicle pups were intubated with a choline chloride solution or vehicle daily from PD 2 to 21, whereas the non-treated pups were handled daily but not intubated. On PD 45, subjects were tested on a visuospatial discrimination task. Ethanol-exposed subjects who were not treated neonatally with choline committed a significantly greater number of errors both during acquisition and during delayed discrimination training compared to both PF and LC controls. Neonatal choline treatment significantly improved performance on the discrimination task in all groups; however, the beneficial effects of choline were significantly larger in ethanol-exposed subjects. Indeed, the performance of ethanol-exposed pups treated with neonatal choline did not differ from any of the PF or LC groups on any measure. Thus, early postnatal choline supplementation significantly attenuated the effects of prenatal alcohol on this learning task. Importantly, these effects were not due to the acute effects of choline, but rather to long-term changes in brain and behavioral development. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects.
Choline supplementation during prenatal development reduces proactive interference in spatial memory
1999, Developmental Brain Research
Previous research has demonstrated that increasing dietary choline during early development can have long-lasting effects on cholinergic (Ch) function that are correlated with improvement of spatial memory ability in rats. The present study is designed to further our understanding of these organizational changes in brain and behavior by examining the effects of spaced vs. massed trials. A third of the rats (n=10) were supplemented with choline chloride prenatally by adding it to the drinking water of their dams. Another third were made deficient of choline during early development by removing choline from the dams diet. The remaining rats served as untreated controls. Postnatally, the offspring were maintained on a choline-sufficient diet and at 120 days of age they began 12-arm radial maze training. The maze data revealed two major effects of early choline availability: (1) Both choline-supplemented and choline-deficient rats performed more accurately than control littermates when trials were spaced. These differences in spatial ability did not appear to be a function of differential response or cue-use strategies. (2) Choline-supplemented rats showed little proactive interference when trials were massed; whereas control rats demonstrated moderate levels and choline-deficient rats exhibited high levels of proactive interference as a function of massed trials. These data suggest that the behavioral consequences of early dietary availability of choline may involve the modification of the discriminative abilities used to attend to stimuli that demarcate the end of one trial and the start of another as well as the capacity for remembering the locations that have been visited during a trial.
The influences of rearing environment and neonatal choline dietary supplementation on spatial learning and memory in adult rats
1999, Behavioural Brain Research
The facilitative effects of early environmental enrichment and perinatal choline chloride dietary supplementation on adult rat spatial learning and memory were examined using delayed match-to-place (DMTP) and delayed spatial win-shift (DSWSh) discrimination tasks. Animals were either maintained in a standard lighted colony (LR) or were given supplementary exposure to a complex environment (CR) for 2-h daily from 20 to 90 days of age. In each case, half the animals were exposed to the choline supplementation both prenatally (through the diet of pregnant rats) and postnatally (subcutaneous injection) for 24 days. In the first experiment, all 90-day-old rats were given trials in which they first found a hidden platform in a Morris water maze (MWM) in a particular location (acquisition trial), and then were required to remember that position 10 min later (test trial). Both environmental enrichment and early diet had significant impacts on performance. CR animals, given neonatal choline pretreatment, found the platform on test trials significantly faster than any of the other groups. CR animals exposed to the control saline diet showed better retention than did the LR animals given the early choline diet, which in turn, were superior to animals given neither environmental enrichment nor choline. All animals were subsequently tested in the same paradigm immediately following atropine sulfate injections. The atropine eliminated the difference between the four groups of animals on test trials. In a second experiment, both CR, and neonatal choline treatment facilitated performance on a DSWSh radial arm maze (RAM) task previously found to be sensitive to hippocampal and/or medial prefrontal lesions. Performance differences between groups were facilitated by the anticholinesterase drug, tacrine and attenuated by the cholinergic antagonist, Atropine. The present study extends the descriptions of long-term functional enhancements produced by perinatal choline supplementation and environmental enrichment and to relate these effects to common modifications to targets of cholinergic basal forebrain systems.
Dietary choline manipulations and behavioural modifications in rats in the early stages of aging
1991, Progress in Neuropsychopharmacology and Biological Psychiatry
Fundaro, Anna and Alessandro Paschero: Dietary Choline Manipulations and Behavioural Modifications in Rats in the Early Stages of Aging. Prog. Neuro-Psychopharmacol.& Biol. Psychiat. 1991, $15$ (5): 677–688. o
1. 1.
  1. Behavioural effects of chronic manipulations of dietary choline in rats in the early stages of aging are reported. Rats were maintained on choline-deficient, low-choline and high-choline enriched diets. Two schedules of operant conditioning, representing “learning” situations, plus an open field session were studied.
2. 2.
  2. In the “temporal discrimination” test, the low-choline enriched group performed significantly better than controls while the deficient—choline group worse. The high—choline enriched group performed better than controls only in the second part of the test (where there was a stabilisation in behaviour).
3. 3.
  3. In the “extinction” trials the high-choline enriched group retarded, while deficient—choline accelerated the extinction. In the open field sessions only the deficient-choline group, for the number of squares crossed, significantly differed from controls.
4. 4.
  4. These observations lead us to suggest a general depressive effect in the rats on a choline—deficient diet, whereas with dietary choline supplements the effects on “learning” situations can be variable depending, on a large measure, on the test chosen.

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Brief communicationEffects of dietary choline on memory and brain chemistry in aged mice

Abstract

Mech Ageing Dev

Physiol Behav

Neurobiol Aging

Prog Brain Res

Life Sci

J Biol Chem

Anal Biochem

Anal Biochem

Mech Ageing Dev

The cholinergic hypothesis of geriatric memory dysfunction

Science

Brief communication
Effects of dietary choline on memory and brain chemistry in aged mice