Effects of quercetin on spatial memory, hippocampal antioxidant defense and BDNF concentration in a rat model of Parkinson’s disease: An electrophysiological study

Document Type : Original Research Article


1 Department of Food Sciences and Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

2 Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

3 Deputy of Research and Technology, Zahedan University of Medical Sciences, Zahedan, Iran


Objective: Quercetin is one of the most popular flavonoid with protective effects against neural damages in Parkinson's disease (PD). We assessed the effect of quercetin administration on memory and motor function, hippocampal ‎ oxidative stress and brain-derived neurotrophic factor (BDNF) level in a 6-OHDA-induced Parkinson's rat model.
Material and Methods: The animals were divided into the following five groups (n=8): control, sham-surgery (sham), lesion (PD), and lesion animals treated with quercetin at doses of 10 (Q10) and 25 (Q25) mg/kg. For induction of a model of PD, 6-OHDA was injected into the striatum of rats. The effects of quercetin were investigated on spatial memory, hippocampal BDNF and malondialdehyde (MDA) levels, and total antioxidant capacity (TAC). Spatial memory was assessed by Morris water maze test, and the neuronal firing frequency in hippocampal dentate gyrus (HDG) was evaluated by single-unit recordings.
Results: Mean path length and latency time, rotational behavior and hippocampal MDA concentration were significantly increased, while time spent in the goal quadrant, swimming speed, spike rate, and hippocampal levels of TAC and BDNF were significantly decreased in the PD group compared to the sham group (p<0.01 to p<0.001). Quercetin treatment significantly enhanced time spent in goal quadrant (p<0.05), swimming speed (p<0.001) and spike rate (p<0.01), improved hippocampal TAC (p<0.05 to p<0.001) and BDNF (p<0.01 to p<0.001) level, and decreased mean path length (p<0.001), latency time (p<0.05 to p<0.001), rotational behavior and hippocampal MDA concentration (p<0.05).
Conclusion: The cognitive-enhancing effect of quercetin might be due to its antioxidant effects in the hippocampus.


Amália PM, Possa MN, Augusto MC,
Francisca LSJDd, sciences. 2007. Quercetin
prevents oxidative stress in cirrhotic rats.
Dig Dis Sci, 52: 2616-2621.
Arbabi E, Hamidi G, Talaei SA, Salami
MJIjobms. 2016. Estrogen agonist genistein
differentially influences the cognitive and
motor disorders in an ovariectomized animal
model of Parkinsonism. Iran J Basic Med
Sci, 19: 1285.
Ay M, Luo J, Langley M, Jin H, Anantharam V,
Kanthasamy A, Kanthasamy AG. 2017.
Molecular mechanisms underlying
protective effects of quercetin against
mitochondrial dysfunction and progressive
dopaminergic neurodegeneration in cell
culture and MitoPark transgenic mouse
models of Parkinson's Disease. J
Neurochem, 141: 766-782.
Barichella M, Cereda E, Pezzoli GJMd. 2009.
Major nutritional issues in the management
of Parkinson's disease. Mov Disord, 24:
Cattaneo E, Zuccato C, Tartari M. 2005.
Normal huntingtin function: an alternative
approach to Huntington's disease. Nat Rev
Neurosci, 6: 919-930.
Chang K-H, Chen C-M. 2020. The Role of
Oxidative Stress in Parkinson’s Disease.
Antioxidants, 9: 597.
Creese I, Burt DR, Snyder SH. 1977. Dopamine
receptor binding enhancement accompanies
lesion-induced behavioral supersensitivity.
Science, 197: 596-598.
De Leonibus E, Pascucci T, Lopez S, Oliverio
A, Amalric M, Mele AJP. 2007. Spatial
deficits in a mouse model of Parkinson
disease. Psychopharmacology, 194: 517-
Guo JD, Zhao X, Li Y, Li GR, Liu XL. 2018.
Damage to dopaminergic neurons by
oxidative stress in Parkinson's disease. Int J
Mol Med, 41: 1817-1825.
Haleagrahara N, Siew CJ, Mitra NK, Kumari
MJNl. 2011. Neuroprotective effect of
bioflavonoid quercetin in 6-
hydroxydopamine-induced oxidative stress
biomarkers in the rat striatum. Neurosci
Lett, 500: 139-143.
Hu LF, Lu M, Tiong CX, Dawe GS, Hu G, Bian
JSJAc. 2010. Neuroprotective effects of
hydrogen sulfide on Parkinson’s disease rat
models. Aging cell, 9: 135-146.
Naghizadeh et al.
AJP, Vol. 11, No. 6, Nov-Dec 2021 608
Huang J, Zhu M, Tao Y, Wang S, Chen J, Sun
W, Li SJJoP, Pharmacology. 2012.
Therapeutic properties of quercetin on
monosodium urate crystal‐induced
inflammation in rat. J Pharm Pharmacol, 64:
Karuppagounder S, Madathil S, Pandey M,
Haobam R, Rajamma U, Mohanakumar K.
2013. Quercetin up-regulates mitochondrial
complex-I activity to protect against
programmed cell death in rotenone model of
Parkinson’s disease in rats. Neuroscience,
236: 136-148.
Kim JJ, Clark RE, Thompson RF. 1995.
Hippocampectomy impairs the memory of
recently, but not remotely, acquired trace
eyeblink conditioned responses. Behavioral
neuroscience, 109: 195.
Kumar R, Agarwal AK, Seth PKJJon. 1995.
Free radical‐generated neurotoxicity of 6‐
hydroxydopamine. J Neurochem, 64: 1703-
Lev N, Barhum Y, Ben-Zur T, Melamed E,
Steiner I, Offen D. 2013. Knocking out DJ1 attenuates astrocytes neuroprotection
against 6-hydroxydopamine toxicity. J Mol
Neurosci, 50: 542-550.
Miranda M, Morici JF, Zanoni MB,
Bekinschtein P. 2019. Brain-derived
neurotrophic factor: a key molecule for
memory in the healthy and the pathological
brain. Frontiers in cellular neuroscience, 13:
Mirshekar MA, Sarkaki A, Farbood Y, Naseri
MKG, Badavi M, Mansouri MT,
Haghparast A. 2018. Neuroprotective
effects of gallic acid in a rat model of
traumatic brain injury: behavioral,
electrophysiological, and molecular studies.
Iran J Basic Med Sci, 21: 1056.
Narayanan NS, Rodnitzky RL, Uc EY. 2013.
Prefrontal dopamine signaling and cognitive
symptoms of Parkinson’s disease. Rev
Neurosci, 24: 267-278.
Nokia MS, Gureviciene I, Waselius T, Tanila
H, Penttonen M. 2017. Hippocampal
electrical stimulation disrupts associative
learning when targeted at dentate spikes. J
Physiol, 595: 4961-4971.
O’Neill M, Brown VJJNol, memory. 2007. The
effect of striatal dopamine depletion and the
adenosine A2A antagonist KW-6002 on
reversal learning in rats. Neurobiol Learn
Mem, 88: 75-81.
Ola MS, Ahmed MM, Shams S, Al-Rejaie SS.
2017. Neuroprotective effects of quercetin
in diabetic rat retina. Saudi J Biol Sci, 24:
Paxinos G, Watson C 2006. The rat brain in
stereotaxic coordinates: hard cover edition,
Academic press.
Prasad J, Baitharu I, Sharma AK, Dutta R,
Prasad D, Singh S. 2013. Quercetin reverses
hypobaric hypoxia-induced hippocampal
neurodegeneration and improves memory
function in the rat. High Alt Med Biol, 14:
Pu F, Mishima K, Irie K, Motohashi K, Tanaka
Y, Orito K, Egawa T, Kitamura Y, Egashira
N, Iwasaki K. 2007. Neuroprotective effects
of quercetin and rutin on spatial memory
impairment in an 8-arm radial maze task and
neuronal death induced by repeated cerebral
ischemia in rats. J Pharmacol Sci, 4: 329-
Rahmani F, Saghazadeh A, Rahmani M,
Teixeira AL, Rezaei N, Aghamollaii V,
Ardebili HE. 2019. Plasma levels of brainderived neurotrophic factor in patients with
Parkinson disease: A systematic review and
meta-analysis. Brain Res, 1704: 127-136.
Rahvar M, Owji AA, Mashayekhi FJ. 2018.
Effect of quercetin on the brain-derived
neurotrophic factor gene expression in the
rat brain. Bratisl Lek Listy, 119: 28-31.
Russo-Neustadt AA, Chen MJ. 2005. Brainderived neurotrophic factor and
antidepressant activity. Curr Pharm Des, 11:
Schober A. 2004. Classic toxin-induced animal
models of Parkinson's disease: 6-OHDA and
MPTP. Cell Tissue Res, 318: 215-224.
Schwarting R, Huston J. 1996. The unilateral 6-
hydroxydopamine lesion model in
behavioral brain research. Analysis of
functional deficits, recovery and treatments.
Prog Neurobiol, 50: 275-331.
Selvakumar K, Bavithra S, Krishnamoorthy G,
Arunakaran J. 2018. Impact of quercetin on
tight junctional proteins and BDNF
signaling molecules in hippocampus of
PCBs-exposed rats. Interdiscip Toxicol, 11:
Shim JS, Kim HG, Ju MS, Choi JG, Jeong SY,
Oh MS. 2009. Effects of the hook of Uncaria
rhynchophylla on neurotoxicity in the 6-
hydroxydopamine model of Parkinson's
disease. J Ethnopharmacol, 126: 361-365.
Sriraksa N, Wattanathorn J, Muchimapura S,
Tiamkao S, Brown K, Chaisiwamongkol
Effect of quercetin on cognition in a rat model of Parkinson’s disease
AJP, Vol. 11, No. 6, Nov-Dec 2021 609
KJE-BC, Medicine A. 2012. Cognitiveenhancing effect of quercetin in a rat model
of Parkinson's disease induced by 6-
hydroxydopamine. BMC Complement
Altern Med, 2012.
Wang Q, Liu J, Guo Y, Dong G, Zou W, Chen
Z. 2019. Association between BDNF
G196A (Val66Met) polymorphism and
cognitive impairment in patients with
Parkinson's disease: a meta-analysis. Braz J
Med Biol Res, 52: e8443.