Systematic review of the literature on vitamin A and memory

Fragoso, Yara Dadalti; Campos, Niklas Söderberg; Tenrreiro, Breno Faria; Guillen, Fernanda Jussio

doi:10.1590/S1980-57642012DN06040005

ABSTRACT

Background:

Over the last 30 years, a variety of studies reporting the effects of vitamin A on memory have been published.

Objective:

To perform a rigorous systematic review of the literature on vitamin A and memory in order to organize evidence-based data on the subject.

Methods:

Four authors carried out the systematic review in accordance with strict guidelines. The terms "vitamin A" OR "retinol" OR "retinoic acid" AND "memory" OR "cognition" OR "Alzheimer" were searched in virtually all medical research databases.

Results:

From 236 studies containing the key words, 44 were selected for this review, numbering 10 reviews and 34 original articles. Most studies used animal models for studying vitamin A and cognition. Birds, mice and rats were more frequently employed whereas human studies accounted for only two reports on brain tissue from autopsies and one on the role of isotretinoin in cognition among individuals taking this medication to treat acne.

Conclusion:

Vitamin A may be an important and viable complement in the treatment and prevention of Alzheimer's disease. Clinical trials are imperative and, at present, there is no evidence-based data to recommend vitamin A supplementation for the prevention or treatment of Alzheimer's disease.

Key words:
vitamin A; retinol; retinoic acid; memory; cognition; Alzheimer

RESUMO

Introdução:

Uma variedade de artigos relatando efeitos da vitamina A na memória foram publicados nos últimos 30 anos.

Objetivo:

Realizar uma revisão sistemática rigorosa da literatura sobre vitamina A e memória, visando organizar os dados com base em evidência.

Métodos:

Quatro autores realizaram a revisão sistemática de acordo com recomendações específicas para tal. Os termos "vitamin A" OR "retinol" OR "retinoic acid" AND "memory" OR "cognition" OR "Alzheimer" foram utilizados na pesquisa de praticamente todas as bases de dados de publicações médicas.

Resultados:

Dos 236 artigos contendo as palavras específicas de busca, 44 foram selecionados para esta revisão, sendo10 revisões e 34 artigos originais. A maioria dos estudos utilizou modelos animais para avaliar vitamina A e cognição. Pássaros, camundongos e ratos foram mais frequentemente utilizados, enquanto estudos com humanos foram apenas dois relatando dados de necrópsia de cérebro humano e um sobre o papel da isotretinoína na cognição de indivíduos que estavam usando esta medicação para tratar acne.

Conclusão:

Vitamina A pode ser um complemento importante e viável no tratamento e prevenção da doença de Alzheimer. Estudos clínicos são imperativos e, no momento, não existe evidência científica que recomende suplementação de vitamina A na prevenção ou tratamento da doença de Alzheimer.

Palavras-chave:
vitamina A; retinol; ácido retinóico; memória; cognição; Alzheimer

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Full text available only in PDF format.

REFERENCES

Bendich A, Olson JA. Biological actions of carotenoids. FASEB J 1989; 3:1927-1932.
Napoli JL. Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta 1999;1440:139-162.
Mic FA, Haselbeck RJ, Cuenca AE, Duester G. Novel retinoic acid generating activities in the neural tube and heart identified by conditional rescue of Raldh2 null mutant mice. Development 2002;129:2271-2282.
Arlappa N. Vitamin A deficiency is still a public health problem in India. Indian Pediatr 2011;48:853-854.
Jiang J, Toschke AM, von Kries R, Koletzko B, Lin L. Vitamin A status among children in China. Public Health Nutr 2006;9:955-960.
Olson CR, Mello CV. Significance of vitamin A to brain function, behavior and learning. Mol Nutr Food Res 2010;54:489-495.
Imdad A, Yakoob MY, Sudfeld C, Haider BA, Black RE, Bhutta ZA. Impact of vitamin A supplementation on infant and childhood mortality. BMC Public Health 2011;11(Suppl 3):S20.
Barbosa Chagas C, Ramalho A, de Carvalho Padilha P, Delia Libera B, Saunders C. Reduction of vitamin A deficiency and anemia in pregnancy after implementing proposed prenatal nutritional assistance. Nutr Hosp 2011;26:843-850.
Lam HS, Chow CM, Poon WT, et al. Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children. Pediatrics 2006;118:820-824.
Duerbeck NB, Dowling DD. Vitamin A: too much of a good thing? Obstet Gynecol Surv 2012;67:122-128.
Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, CAyley AC. Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease. Age ageing 1992;21:91-94.
Obulesu M, Dowlathabad MR, Bramhachari PV. Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models. Neurochem Int 2011; 59:535-541.
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group - Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Open Med 2009;3:123-30.
Schardt C, Adams MB, Owens T, Keitz S, Fontelo P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med Inform Decis Mak 2007;7:16.
Enderlin V, Pallet V, Alfos S, Dargelos E, Jaffard R, Garcin H, Higueret P. Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment. Neurosci Lett 1997;229:125-129.
Connor MJ, Sidell N. Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural cells. Mol Chem Neuropathol 1997;30:239-252.
Chiang MY, Misner D, Kempermann G, et al. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron 1998;21:1353-1361.
Denisenko-Nehrbass NI, Jarvis E, Scharff C, Nottebohm F, Mello CV. Site-specific retinoic acid production in the brain of adult songbirds. Neuron 2000;27:359-370.
Alfos S, Boucheron C, Pallet V, et al. A retinoic acid receptor antagonist suppresses brain retinoic acid receptor overexpression and reverses a working memory deficit induced by chronic ethanol consumption in mice. Alcohol Clin Exp Res 2001;25:1506-1514.
Etchamendy N, Enderlin V, Marighetto A, et al. Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling. J Neurosci 2001;21:6423-6429.
Misner DL, Jacobs S, Shimizu Y, et al. Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proc Natl Acad Sci USA 2001;98:11714-11719.
Cocco S, Diaz G, Stancampiano R, Diana A, et al. Vitamin A deficiency produces spatial learning and memory impairment in rats. Neuroscience 2002;115:475-482.
Etchamendy N, Enderlin V, Marighetto A, Pallet V, Higueret P, Jaffard R. Vitamin A deficiency and relational memory deficit in adult mice: relationships with changes in brain retinoid signalling. Behav Brain Res 2003;145:37-49.
Goodman AB, Pardee AB. Evidence for defective retinoid transport and function in late onset Alzheimer's disease. Proc Natl Acad Sci USA 2003;100:2901-2905.
Corcoran JP, So PL, Maden M. Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain. Eur J Neurosci 2004;20:896-902.
Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M. Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro. Exp Neurol 2004;189:380-392.
Craft NE, Haitema TB, Garnett KM, Fitch KA, Dorey CK. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging 2004;8:156-162.
Wietrzych M, Meziane H, Sutter A, et al. . Working memory deficits in retinoid X receptor gamma-deficient mice. Learn Mem 2005;12:318-326.
Lane MA, Bailey SJ. Role of retinoid signalling in the adult brain. Prog Neurobiol 2005;75:275-293.
Goodman AB. Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. J Cell Physiol 2006;209:598-603.
Hernández-Pinto AM, Puebla-Jiménez L, Arilla-Ferreiro E. A vitamin A-free diet results in impairment of the rat hippocampal somatostatinergic system. Neuroscience 2006;141:851-861.
McCaffery P, Zhang J, Crandall JE. Retinoic acid signaling and function in the adult hippocampus. J Neurobiol 2006;66:780-791.
Mao CT, Li TY, Qu P, Zhao Y, Wang R, Liu YX. Effects of early intervention on learning and memory in young rats of marginal vitamin A deficiency and its mechanism. Zhonghua Er Ke Za Zhi 2006;44:15-20.
Dräger UC. Retinoic acid signaling in the functioning brain. Sci STKE 2006;324:10.
Kheirvari S, Uezu K, Sakai T, et al. Increased nerve growth factor by zinc supplementation with concurrent vitamin A deficiency does not improve memory performance in mice. J Nutr Sci Vitaminol (Tokyo) 2006;52:421-427.
Stancampiano R, Carta M, Fadda F. Vitamin A deficiency affects neither frontocortical acetylcholine nor working memory. Neuroreport 2007; 18:241-243.
Tafti M, Ghyselinck NB. Functional implication of the vitamin A signaling pathway in the brain. Arch Neurol 2007;64:1706-1711.
Ono K, Yamada M. Vitamin A potently destabilizes preformed alpha-synuclein fibrils in vitro: implications for Lewy body diseases. Neurobiol Dis 2007;25:446-454.
Ding Y, Qiao A, Wang Z, et al. Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci 2008;28:11622-11634.
Bonnet E, Touyarot K, Alfos S, Pallet V, Higueret P, Abrous DN. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats. PLoS One 2008;3:3487.
Mingaud F, Mormede C, Etchamendy N, et al. Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice. J Neurosci 2008;28:279-291.
Fonzo LS, Golini RS, Delgado SM, et al. . Temporal patterns of lipoperoxidation and antioxidant enzymes are modified in the hippocampus of vitamin A-deficient rats. Hippocampus 2009;19:869-880.
Yang Z, Xi J, Li J, Qu W. Biphasic effect of citral, a flavoring and scenting agent, on spatial learning and memory in rats. Pharmacol Biochem Behav 2009;93:391-396.
Munetsuna E, Hojo Y, Hattori M, et al. Retinoic acid stimulates 17beta-estradiol and testosterone synthesis in rat hippocampal slice cultures. Endocrinology 2009;150:4260-4269.
Lee HP, Casadesus G, Zhu X, et al. All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease. Expert Rev Neurother 2009;9:1615-1621.
Luo T, Wagner E, Dräger UC. Integrating retinoic acid signaling with brain function. Dev Psychol 2009;45:139-150.
Olson CR, Mello CV. Significance of vitamin A to brain function, behavior and learning. Mol Nutr Food Res 2010;54:489-495.
Zhang X, Chen K, Chen J, Liu YX, Qu P, Li TY. Effect of marginal vitamin A deficiency during pregnancy on retinoic acid receptors and N-methyl-D-aspartate receptor expression in the offspring of rats. J Nutr Biochem 2011;22:1112-1120.
Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, et al. Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol Psychiatry 2011;69:788-794.
Ormerod AD, Thind CK, Rice SA, Reid IC, Williams JH, McCaffery PJ. Influence of isotretinoin on hippocampal-based learning in human subjects. Psychopharmacology (Berl). 2012;221: 667-674.
Ono K, Yamada M. Vitamin A and Alzheimer's disease. Geriatr Gerontol Int 2012;12:180-188.
Jiang W, Yu Q, Gong M, et al. Vitamin A deficiency impairs postnatal cognitive function via inhibition of neuronal calcium excitability in hippocampus. J Neurochem 2012;121:932-943.
Golini RS, Delgado SM, Navigatore Fonzo LS, Ponce IT, Lacoste MG, Anzulovich AC. Daily patterns of clock and cognition-related factors are modified in the hippocampus of vitamin A-deficient rats. Hippocampus 2012 Mar 21. [Epub ahead of print]
Fragoso YD, Shearer KD, Sementilli A, de Carvalho LV, McCaffery PJ. High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus. Brain Struct Funct. 2012;217:473-483.
Guo M, Bryant J, Sultana S, Jones O, Royal W. Effects of Vitamin A Deficiency and Opioids on Parvalbumin+ Interneurons in the Hippocampus of the HIV-1 Transgenic Rat. Curr HIV Res 2012;10:463-468.
Nomoto M, Takeda Y, Uchida S, et al. . Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity. Mol Brain 2012 ;5:8.
Goodman T, Crandall JE, Nanescu SE, et al. Patterning of retinoic acid signaling and cell proliferation in the hippocampus. Hippocampus 2012; 22:2171-2183.

Publication Dates

Publication in this collection
Oct-Dec 2012

History

Received
18 Aug 2012
Accepted
02 Nov 2012

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Bendich A, Olson JA. Biological actions of carotenoids. FASEB J 1989; 3:1927-1932.

[2] Napoli JL. Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta 1999;1440:139-162.

[3] Mic FA, Haselbeck RJ, Cuenca AE, Duester G. Novel retinoic acid generating activities in the neural tube and heart identified by conditional rescue of Raldh2 null mutant mice. Development 2002;129:2271-2282.

[4] Arlappa N. Vitamin A deficiency is still a public health problem in India. Indian Pediatr 2011;48:853-854.

[5] Jiang J, Toschke AM, von Kries R, Koletzko B, Lin L. Vitamin A status among children in China. Public Health Nutr 2006;9:955-960.

[6] Olson CR, Mello CV. Significance of vitamin A to brain function, behavior and learning. Mol Nutr Food Res 2010;54:489-495.

[7] Imdad A, Yakoob MY, Sudfeld C, Haider BA, Black RE, Bhutta ZA. Impact of vitamin A supplementation on infant and childhood mortality. BMC Public Health 2011;11(Suppl 3):S20.

[8] Barbosa Chagas C, Ramalho A, de Carvalho Padilha P, Delia Libera B, Saunders C. Reduction of vitamin A deficiency and anemia in pregnancy after implementing proposed prenatal nutritional assistance. Nutr Hosp 2011;26:843-850.

[9] Lam HS, Chow CM, Poon WT, et al. Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children. Pediatrics 2006;118:820-824.

[10] Duerbeck NB, Dowling DD. Vitamin A: too much of a good thing? Obstet Gynecol Surv 2012;67:122-128.

[11] Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, CAyley AC. Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease. Age ageing 1992;21:91-94.

[12] Obulesu M, Dowlathabad MR, Bramhachari PV. Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models. Neurochem Int 2011; 59:535-541.

[13] Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group - Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Open Med 2009;3:123-30.

[14] Schardt C, Adams MB, Owens T, Keitz S, Fontelo P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med Inform Decis Mak 2007;7:16.

[15] Enderlin V, Pallet V, Alfos S, Dargelos E, Jaffard R, Garcin H, Higueret P. Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment. Neurosci Lett 1997;229:125-129.

[16] Connor MJ, Sidell N. Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural cells. Mol Chem Neuropathol 1997;30:239-252.

[17] Chiang MY, Misner D, Kempermann G, et al. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron 1998;21:1353-1361.

[18] Denisenko-Nehrbass NI, Jarvis E, Scharff C, Nottebohm F, Mello CV. Site-specific retinoic acid production in the brain of adult songbirds. Neuron 2000;27:359-370.

[19] Alfos S, Boucheron C, Pallet V, et al. A retinoic acid receptor antagonist suppresses brain retinoic acid receptor overexpression and reverses a working memory deficit induced by chronic ethanol consumption in mice. Alcohol Clin Exp Res 2001;25:1506-1514.

[20] Etchamendy N, Enderlin V, Marighetto A, et al. Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling. J Neurosci 2001;21:6423-6429.

[21] Misner DL, Jacobs S, Shimizu Y, et al. Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proc Natl Acad Sci USA 2001;98:11714-11719.

[22] Cocco S, Diaz G, Stancampiano R, Diana A, et al. Vitamin A deficiency produces spatial learning and memory impairment in rats. Neuroscience 2002;115:475-482.

[23] Etchamendy N, Enderlin V, Marighetto A, Pallet V, Higueret P, Jaffard R. Vitamin A deficiency and relational memory deficit in adult mice: relationships with changes in brain retinoid signalling. Behav Brain Res 2003;145:37-49.

[24] Goodman AB, Pardee AB. Evidence for defective retinoid transport and function in late onset Alzheimer's disease. Proc Natl Acad Sci USA 2003;100:2901-2905.

[25] Corcoran JP, So PL, Maden M. Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain. Eur J Neurosci 2004;20:896-902.

[26] Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M. Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro. Exp Neurol 2004;189:380-392.

[27] Craft NE, Haitema TB, Garnett KM, Fitch KA, Dorey CK. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging 2004;8:156-162.

[28] Wietrzych M, Meziane H, Sutter A, et al. . Working memory deficits in retinoid X receptor gamma-deficient mice. Learn Mem 2005;12:318-326.

[29] Lane MA, Bailey SJ. Role of retinoid signalling in the adult brain. Prog Neurobiol 2005;75:275-293.

[30] Goodman AB. Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. J Cell Physiol 2006;209:598-603.

[31] Hernández-Pinto AM, Puebla-Jiménez L, Arilla-Ferreiro E. A vitamin A-free diet results in impairment of the rat hippocampal somatostatinergic system. Neuroscience 2006;141:851-861.

[32] McCaffery P, Zhang J, Crandall JE. Retinoic acid signaling and function in the adult hippocampus. J Neurobiol 2006;66:780-791.

[33] Mao CT, Li TY, Qu P, Zhao Y, Wang R, Liu YX. Effects of early intervention on learning and memory in young rats of marginal vitamin A deficiency and its mechanism. Zhonghua Er Ke Za Zhi 2006;44:15-20.

[34] Dräger UC. Retinoic acid signaling in the functioning brain. Sci STKE 2006;324:10.

[35] Kheirvari S, Uezu K, Sakai T, et al. Increased nerve growth factor by zinc supplementation with concurrent vitamin A deficiency does not improve memory performance in mice. J Nutr Sci Vitaminol (Tokyo) 2006;52:421-427.

[36] Stancampiano R, Carta M, Fadda F. Vitamin A deficiency affects neither frontocortical acetylcholine nor working memory. Neuroreport 2007; 18:241-243.

[37] Tafti M, Ghyselinck NB. Functional implication of the vitamin A signaling pathway in the brain. Arch Neurol 2007;64:1706-1711.

[38] Ono K, Yamada M. Vitamin A potently destabilizes preformed alpha-synuclein fibrils in vitro: implications for Lewy body diseases. Neurobiol Dis 2007;25:446-454.

[39] Ding Y, Qiao A, Wang Z, et al. Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci 2008;28:11622-11634.

[40] Bonnet E, Touyarot K, Alfos S, Pallet V, Higueret P, Abrous DN. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats. PLoS One 2008;3:3487.

[41] Mingaud F, Mormede C, Etchamendy N, et al. Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice. J Neurosci 2008;28:279-291.

[42] Fonzo LS, Golini RS, Delgado SM, et al. . Temporal patterns of lipoperoxidation and antioxidant enzymes are modified in the hippocampus of vitamin A-deficient rats. Hippocampus 2009;19:869-880.

[43] Yang Z, Xi J, Li J, Qu W. Biphasic effect of citral, a flavoring and scenting agent, on spatial learning and memory in rats. Pharmacol Biochem Behav 2009;93:391-396.

[44] Munetsuna E, Hojo Y, Hattori M, et al. Retinoic acid stimulates 17beta-estradiol and testosterone synthesis in rat hippocampal slice cultures. Endocrinology 2009;150:4260-4269.

[45] Lee HP, Casadesus G, Zhu X, et al. All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease. Expert Rev Neurother 2009;9:1615-1621.

[46] Luo T, Wagner E, Dräger UC. Integrating retinoic acid signaling with brain function. Dev Psychol 2009;45:139-150.

[47] Olson CR, Mello CV. Significance of vitamin A to brain function, behavior and learning. Mol Nutr Food Res 2010;54:489-495.

[48] Zhang X, Chen K, Chen J, Liu YX, Qu P, Li TY. Effect of marginal vitamin A deficiency during pregnancy on retinoic acid receptors and N-methyl-D-aspartate receptor expression in the offspring of rats. J Nutr Biochem 2011;22:1112-1120.

[49] Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, et al. Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol Psychiatry 2011;69:788-794.

[50] Ormerod AD, Thind CK, Rice SA, Reid IC, Williams JH, McCaffery PJ. Influence of isotretinoin on hippocampal-based learning in human subjects. Psychopharmacology (Berl). 2012;221: 667-674.

[51] Ono K, Yamada M. Vitamin A and Alzheimer's disease. Geriatr Gerontol Int 2012;12:180-188.

[52] Jiang W, Yu Q, Gong M, et al. Vitamin A deficiency impairs postnatal cognitive function via inhibition of neuronal calcium excitability in hippocampus. J Neurochem 2012;121:932-943.

[53] Golini RS, Delgado SM, Navigatore Fonzo LS, Ponce IT, Lacoste MG, Anzulovich AC. Daily patterns of clock and cognition-related factors are modified in the hippocampus of vitamin A-deficient rats. Hippocampus 2012 Mar 21. [Epub ahead of print]

[54] Fragoso YD, Shearer KD, Sementilli A, de Carvalho LV, McCaffery PJ. High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus. Brain Struct Funct. 2012;217:473-483.

[55] Guo M, Bryant J, Sultana S, Jones O, Royal W. Effects of Vitamin A Deficiency and Opioids on Parvalbumin+ Interneurons in the Hippocampus of the HIV-1 Transgenic Rat. Curr HIV Res 2012;10:463-468.

[56] Nomoto M, Takeda Y, Uchida S, et al. . Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity. Mol Brain 2012 ;5:8.

[57] Goodman T, Crandall JE, Nanescu SE, et al. Patterning of retinoic acid signaling and cell proliferation in the hippocampus. Hippocampus 2012; 22:2171-2183.

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