Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer’s disease patients

Patients with Alzheimer’s disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion ‘Quergold’) powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion (‘Mashiro’ white onion) powder. These results indicate that quercetin might influence memory recall.

[1]  T. Inuzuka,et al.  Quercetin reduces eIF2α phosphorylation by GADD34 induction , 2015, Neurobiology of Aging.

[2]  J. R. Ramírez-Pineda,et al.  The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice , 2015, Neuropharmacology.

[3]  P. Fischer,et al.  Mutations in a translation initiation factor identify the target of a memory-enhancing compound , 2015, Science.

[4]  Yong-hui Shi,et al.  Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress , 2015, Physiology & Behavior.

[5]  O. Arancio,et al.  Synaptic Therapy in Alzheimer’s Disease: A CREB-centric Approach , 2015, Neurotherapeutics.

[6]  I. Goudarzi,et al.  Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats , 2014, Behavioural Brain Research.

[7]  Dong-mei Wang,et al.  Effects of Long-Term Treatment with Quercetin on Cognition and Mitochondrial Function in a Mouse Model of Alzheimer’s Disease , 2014, Neurochemical Research.

[8]  S. Josselyn,et al.  Memory recall and modifications by activating neurons with elevated CREB , 2013, Nature Neuroscience.

[9]  K. Nader,et al.  Pharmacological brake-release of mRNA translation enhances cognitive memory , 2013, eLife.

[10]  K. Rosenblum,et al.  ApoE ε4 is associated with eIF2α phosphorylation and impaired learning in young mice , 2013, Neurobiology of Aging.

[11]  W. Canu,et al.  The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial , 2012, Therapeutic advances in psychopharmacology.

[12]  S. Tonegawa,et al.  Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion , 2012, Cell.

[13]  T. Inuzuka,et al.  Endoplasmic reticulum stress enhances γ-secretase activity. , 2011, Biochemical and biophysical research communications.

[14]  M. Kobori,et al.  Autophagy impairment stimulates PS1 expression and γ-secretase activity , 2010, Autophagy.

[15]  Michael S. Fanselow,et al.  From contextual fear to a dynamic view of memory systems , 2010, Trends in Cognitive Sciences.

[16]  B. Ossola,et al.  The multiple faces of quercetin in neuroprotection , 2009, Expert opinion on drug safety.

[17]  W. Scheper,et al.  The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. , 2009, The American journal of pathology.

[18]  Bruno Bontempi,et al.  Selective Erasure of a Fear Memory , 2009, Science.

[19]  D. Bennett,et al.  Phosphorylation of the Translation Initiation Factor eIF2α Increases BACE1 Levels and Promotes Amyloidogenesis , 2008, Neuron.

[20]  M. Wilson,et al.  Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network , 2007, Science.

[21]  T. Nakagawa,et al.  ATF4 regulates γ-secretase activity during amino acid imbalance , 2007 .

[22]  Ki Woong Kim,et al.  Diagnostic Accuracy of Mini-Mental Status Examination and Revised Hasegawa Dementia Scale for Alzheimer’s Disease , 2005, Dementia and Geriatric Cognitive Disorders.

[23]  E. Kandel,et al.  Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins , 2003, Neuron.

[24]  D. Ron,et al.  Feedback Inhibition of the Unfolded Protein Response by GADD34-Mediated Dephosphorylation of eIF2α , 2001, The Journal of cell biology.

[25]  Mary Chen,et al.  Aplysia CREB2 represses long-term facilitation: Relief of repression converts transient facilitation into long-term functional and structural change , 1995, Cell.

[26]  G. Russo,et al.  The flavonoid quercetin in disease prevention and therapy: facts and fancies. , 2012, Biochemical pharmacology.