Vitamin A deficiency produces spatial learning and memory impairment in rats

doi:10.1016/S0306-4522(02)00423-2

Neuroscience

Volume 115, Issue 2, 2 December 2002, Pages 475-482

https://doi.org/10.1016/S0306-4522(02)00423-2 Get rights and content

Abstract

Vitamin A and its derivatives (retinoids) play important roles in many physiological processes. The recent finding of high levels of cellular retinol-binding protein type 1 immunoreactivity, cellular retinoic acid-binding protein type 1 immunoreactivity and the presence of nuclear retinoid receptors in the central nervous system of adult rodents suggests that retinoids may carry out important roles in the adult brain. In consideration of the role of the hippocampus in spatial learning and memory we evaluated the effect of vitamin A deprivation in adult rats on these functions. Following 12 weeks of vitamin A-free diet, rats were trained to acquire a radial-arm maze task. Results show that this diet induced a severe deficit in the spatial learning and memory task. The cognitive impairment was fully restored when vitamin A was replaced in the diet. We also found a significant decrease in hippocampal acetylcholine release induced by scopolamine, assessed using microdialysis technique, and a reduction in the size of hippocampal nuclei of CA1 region in vitamin-deficient rats, compared to rats fed with a vitamin A-sufficient diet. These results demonstrate that vitamin A has a critical role in the learning and memory processes linked to a proper hippocampal functioning.

Section snippets

Animal preparation

Male Sprague–Dawley rats (Harlan, Italy) weighing 85–100 g were used. Animals were housed at a constant temperature of 22±2°C and 60% relative humidity, on a 12-h light/dark cycle (lights on at 7:00 a.m.), food and water available ad libitum. All experimental protocols were applied in strict accordance with international guidelines regulating the use of animals for scientific purposes.

One group of 20 rats received the diet lacking vitamin A (VAD), a second group (10 rats) was fed with standard

Growth curve

Figure 1 shows the effect of 12 weeks of food consumption in VAD and control rats. VAD rats showed a significant reduction in body weight growth with respect to control rats (P<0.0001, by ANOVA). The average difference between body weights of the two groups, calculated from the vertical shift of the log–linearized growth curves, was 43.42±8.52 g (mean±S.D.).

Radial-arm maze performance

Figure 2 shows the number of errors made in the radial maze in VAD, controls, and VAD-replenished rats. Performance improved in all three

Discussion

Results obtained in the present study show that after 12 weeks rats fed with a diet lacking in vitamin A showed clear signs of VAD, such as damaged conjunctival epithelium, loss of body fats and a reduction in body weight growth with respect to control rats. Furthermore, VAD rats displayed impairment in spatial learning. Controls and VAD rats restored to a vitamin A-containing diet learned to choose the correct arm in the radial-arm maze within the 15-day training period, whereas VAD rats

Our results demonstrate an important role of vitamin A in spatial learning and memory function and suggest that the deficit in learning and memory observed in VAD rats may be due both to an impaired cholinergic transmission and to a damaged structure of CA1 neurons. In addition, since VAD rats might have other cognitive dysfunctions, we cannot exclude an impairment in non-spatial learning performance. Further examination of discrete brain areas in conjunction with additional functional tests is

Acknowledgements

The authors would like to thank Dr. L. Carbini and Dr. A.M. Carcassi for their precious collaboration.

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Vitamin A deficiency produces spatial learning and memory impairment in rats

Abstract

Section snippets

Animal preparation

Growth curve

Radial-arm maze performance

Discussion

Acknowledgements

Neurotoxicol. Teratol.

Trends Neurosci.

J. Biol. Chem.

Neuron

Neuroscience

J. Auton. Nerv. Syst.

Eur. J. Pharmacol.

Trend Neurosci.

Neuroscience

Neuroscience

Exp. Neurol.

Brain Res.

Neurosci. Lett.

Life Sci.

Neuroscience

Am. J. Clin. Nutr.

Behav. Brain Res.

Neurobiol. Learn. Mem.

Neuroscience

M2 muscarinic autoreceptors modulate acetylcholine release in the medial pontine reticular formation

J. Pharmacol. Exp. Ther.

The cholinergic hypothesis of geriatric memory disfunction

Science

A synaptic model of memory: long-term potentiation in the hippocampus

Nature

The retinoid signalling pathway: molecular and genetic analyses

Sem. Cell Biol.