Vitamin A deficiency produces spatial learning and memory impairment in rats

Cocco, Stefania; Diaz, Giacomo; Stancampiano, Roberto; Diana, Andrea; Carta, Manolo; Curreli, Rita; Sarais, L; Fadda, F

doi:10.1016/s0306-4522(02)00423-2

Cited by 188 publications

(129 citation statements)

References 41 publications

(43 reference statements)

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“…That vitamin A, and presumably RA, influence LTP and LTD is implied, however, from experiments in which vitamin A deficiency in rats results in loss of long-term synaptic plasticity (Misner et al 2001). Such vitamin A deficiency experiments also lead to defective performance in spatial learning and memory tasks (Cocco et al 2002). Further, in aged mice, where RA signaling in the brain may be reduced, supplemental RA can help reverse an age-related decrease in hippocampal LTP (Etchamendy et al 2001).…”

Section: Retinoic Acid Signaling In the Hippocampusmentioning

confidence: 99%

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

142

149

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Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to the pathophysiology of depression.

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Section: Retinoic Acid Signaling In the Hippocampusmentioning

confidence: 99%

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

142

149

View full text Add to dashboard Cite

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“…Alternatively, the changes in SS-LI content observed here might be, to a certain extent, secondary to the cholinergic dysfunction described by Cocco et al (2002) in VAD. It should be kept in mind that there is a close neuronal interaction between the somatostatinergic and cholinergic systems in the mammalian hippocampus and cortex, as indicated by a number of electrophysiological (Mancillas et al, 1986;Matsuoka et al, 1991), neurochemical (Araujo et al, 1990;Barrios et al, 1990;Gaykema et al, 1991;Zee et al, 1991;Álvaro and Arilla, 1992) and behavioral studies (Haroutunian et al, 1989;Ohno et al, 1993).…”

Section: Discussionmentioning

confidence: 76%

“…Following this period, the rats showed clear signs of VAD such as damaged conjunctival epithelium, loss of body fat and a reduction in body weight gain with respect to control rats, as described by Cocco et al (2002).…”

Section: Discussionmentioning

confidence: 87%

“…The experimental design of VAD was the same as that described by Cocco et al (2002). Briefly, one group of five rats received the diet lacking vitamin A (VAD), whereas a second group (five rats) was fed with standard laboratory chow (controls).…”

Section: Experimental Animalsmentioning

confidence: 99%

“…Mice deprived postnatally of vitamin A (VA), at the age of 12 weeks, showed a reduction of hippocampal CA1 LTP and LTD (Misner et al, 2001). In these VA-deprived mice, the synaptic LTP and LTD activity was restored when animals were returned to a diet containing VA. More recently, it has been found that VA deficiency produces spatial learning and memory impairment in rats (Cocco et al, 2002) and mice (Etchamendy et al,. E-mail address: lilian.puebla@uah.es (E. A. Ferreiro).…”

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confidence: 99%

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A vitamin A-free diet results in impairment of the rat hippocampal somatostatinergic system

2006

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Abstract-Previous studies have revealed the presence of retinoid specific receptors in the hippocampus and have demonstrated that vitamin A deficiency produces a severe deficit in spatial learning and memory which are linked to a proper hippocampal functioning. It is also well known that the tetradecapeptide somatostatin binds to specific receptors in the hippocampus and, when injected into this brain area, facilitates the acquisition of spatial tasks. In addition, depletion of somatostatin by cysteamine impairs acquisition of these tasks. Taken together, these studies support the idea that the hippocampal somatostatinergic system might be regulated by vitamin A. Hence, we evaluated the effects of vitamin A deprivation and subsequent administration of vitamin A on the rat hippocampal somatostatinergic system. Rats fed a vitamin A-free diet exhibited a significant reduction of somatostatin-like immunoreactivity content in the hippocampus whereas the somatostatin mRNA levels were unaltered. Vitamin A deficiency increased the somatostatin receptor density and its dissociation constant. Functional Gi activity as well as the capacity of somatostatin to inhibit basal and forskolin-stimulated adenylyl cyclase activity was decreased in vitamin A deficiency rats as compared with the control animals. All these parameters were fully restored when vitamin A was replaced in the diet. Furthermore, we found that the Gi␣ 1 , Gi␣ 2 and Gi␣ 3 protein levels were unaltered in hippocampal membranes from rats fed a vitamin A-free diet whereas subsequent vitamin A administration to these rats caused a significant increase in the levels of Gi␣1 and Gi␣2. Altogether, the present findings suggest that dietary vitamin A levels modulate the somatostatinergic system in the rat hippocampus.

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Functional Implication of the Vitamin A Signaling Pathway in the Brain

Tafti¹,

Ghyselinck²

2007

Arch Neurol

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Vitamin A is necessary for normal embryonic development, but its role in the adult brain is poorly understood. Vitamin A derivatives, retinoids, are involved in a complex signaling pathway that regulates gene expression and, in the central nervous system, controls neuronal differentiation and neural tube patterning. Although a major functional implication of retinoic signaling has been repeatedly suggested in synaptic plasticity, learning and memory, sleep, schizophrenia, depression, Parkinson disease, and Alzheimer disease, the targets and the underlying mechanisms in the adult brain remain elusive.

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Vitamin A deficiency produces spatial learning and memory impairment in rats

Cited by 188 publications

References 41 publications

The neurobiology of retinoic acid in affective disorders

The neurobiology of retinoic acid in affective disorders

A vitamin A-free diet results in impairment of the rat hippocampal somatostatinergic system

Functional Implication of the Vitamin A Signaling Pathway in the Brain

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