Effects on the Depressive-like Behavior of MPTP-Exposed Female Rats: Apoptosis and α-Synuclein Modulation

Overview

Journal Brain Sci

Publisher MDPI

Date 2025 Jan 24

PMID 39851409

Authors

Anne Suely Pinto Savall

Jhuly Dorneles De Mello

Eduarda Monteiro Fidelis

Vandreza Cardoso Bortolotto

Mustafa Munir Mustafa Dahleh

Gustavo Petri Guerra

Marina Prigol

Robson Puntel

Jean Ramos Boldori

Cristiane Casagrande Denardin

Tuane Bazanella Sampaio

Simone Pinton

Affiliations

Soon will be listed here.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder marked by motor deficits and non-motor symptoms, such as depression, which are associated with dopaminergic loss and α-synuclein aggregation in the brain. This study investigated the neuroprotective effects of a hydroalcoholic extract of the purple fruit of (PFEU) on motor ability and depressive-like behaviors in a PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in female Wistar rats. Rats received intranasal administration of MPTP or vehicle, followed by 14 days of oral administration of PFEU (300 or 2000 mg/kg, administered once daily) or vehicle. Depressive-like behavior was assessed using the splash and forced swimming tests, while motor ability was evaluated using the rotarod and open field tests. On day 15, hippocampal tissue was collected for immunoreactivity analysis. MPTP treatment induced depressive-like behavior, which was significantly reversed by PFEU, as evidenced by increased grooming and decreased immobility. No motor coordination or locomotion deficits were observed. Furthermore, PFEU treatment prevented the MPTP-induced increase in hippocampal α-synuclein, p-p53, and Bax while restoring Bcl-2 levels, suggesting neuroprotective effects through the modulation of apoptotic pathways and α-synuclein. These findings support PFEU's potential as a neuroprotective agent for MPTP-induced depressive-like behavior in female rats, highlighting its molecular mechanisms.

References

Crispino P, Gino M, Barbagelata E, Ciarambino T, Politi C, Ambrosino I . Gender Differences and Quality of Life in Parkinson's Disease. Int J Environ Res Public Health. 2021; 18(1). PMC: 7795924. DOI: 10.3390/ijerph18010198. View

Baba Y, Putzke J, Whaley N, Wszolek Z, Uitti R . Gender and the Parkinson's disease phenotype. J Neurol. 2005; 252(10):1201-5. DOI: 10.1007/s00415-005-0835-7. View

Prediger R, Batista L, Medeiros R, Pandolfo P, Florio J, Takahashi R . The risk is in the air: Intranasal administration of MPTP to rats reproducing clinical features of Parkinson's disease. Exp Neurol. 2006; 202(2):391-403. DOI: 10.1016/j.expneurol.2006.07.001. View

Varadi C . Clinical Features of Parkinson's Disease: The Evolution of Critical Symptoms. Biology (Basel). 2020; 9(5). PMC: 7285080. DOI: 10.3390/biology9050103. View

Porsolt R, Le Pichon M, JALFRE M . Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977; 266(5604):730-2. DOI: 10.1038/266730a0. View

Kwon K, Park S, Kim R, Lee E, Lee M . Associations of cognitive dysfunction with motor and non-motor symptoms in patients with de novo Parkinson's disease. Sci Rep. 2022; 12(1):11461. PMC: 9259652. DOI: 10.1038/s41598-022-15630-8. View

Rozas G, Guerra M, Labandeira-Garcia J . An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. Brain Res Brain Res Protoc. 1998; 2(1):75-84. DOI: 10.1016/s1385-299x(97)00034-2. View

Savall A, Fidelis E, de Mello J, Quines C, Denardin C, Marques L . Neuroprotective effect of Eugenia uniflora against intranasal MPTP-induced memory impairments in rats: The involvement of pro-BDNF/p75 pathway. Life Sci. 2023; 324:121711. DOI: 10.1016/j.lfs.2023.121711. View

Deng M, Liu F, Wang K, Zhang M, Feng Q, Liu J . Association between dietary flavonoid intake and depressive symptoms: A cross-sectional research. Gen Hosp Psychiatry. 2023; 86:75-84. DOI: 10.1016/j.genhosppsych.2023.12.005. View

10.

Ando K, Inoue T, Hikishima K, Komaki Y, Kawai K, Inoue R . Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious.... Behav Pharmacol. 2019; 31(1):45-60. PMC: 6964884. DOI: 10.1097/FBP.0000000000000509. View

11.

Phan J, Stokholm K, Zareba-Paslawska J, Jakobsen S, Vang K, Gjedde A . Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease. Sci Rep. 2017; 7(1):6363. PMC: 5526979. DOI: 10.1038/s41598-017-06724-9. View

12.

McCormack A, Mak S, Shenasa M, Langston W, Forno L, Di Monte D . Pathologic modifications of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated squirrel monkeys. J Neuropathol Exp Neurol. 2008; 67(8):793-802. PMC: 2745435. DOI: 10.1097/NEN.0b013e318180f0bd. View

13.

Jazvinscak Jembrek M, Orsolic N, Mandic L, Sadzak A, Segota S . Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration. Antioxidants (Basel). 2021; 10(10). PMC: 8533072. DOI: 10.3390/antiox10101628. View

14.

Lee M, Stirling W, Xu Y, Xu X, Qui D, Mandir A . Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc Natl Acad Sci U S A. 2002; 99(13):8968-73. PMC: 124407. DOI: 10.1073/pnas.132197599. View

15.

Flores N, Bona N, Luduvico K, de Souza Cardoso J, Soares M, Gamaro G . Eugenia uniflora fruit extract exerts neuroprotective effect on chronic unpredictable stress-induced behavioral and neurochemical changes. J Food Biochem. 2020; 44(10):e13442. DOI: 10.1111/jfbc.13442. View

16.

Isingrini E, Camus V, Le Guisquet A, Pingaud M, Devers S, Belzung C . Association between repeated unpredictable chronic mild stress (UCMS) procedures with a high fat diet: a model of fluoxetine resistance in mice. PLoS One. 2010; 5(4):e10404. PMC: 2861008. DOI: 10.1371/journal.pone.0010404. View

17.

Maulik M, Mitra S, Hunter S, Hunstiger M, Oliver S, Bult-Ito A . Sir-2.1 mediated attenuation of α-synuclein expression by Alaskan bog blueberry polyphenols in a transgenic model of Caenorhabditis elegans. Sci Rep. 2018; 8(1):10216. PMC: 6033853. DOI: 10.1038/s41598-018-26905-4. View

18.

Lee Y, Cha J, Chung S, Yoo H, Sohn Y, Ye B . Beneficial effect of estrogen on nigrostriatal dopaminergic neurons in drug-naïve postmenopausal Parkinson's disease. Sci Rep. 2019; 9(1):10531. PMC: 6642214. DOI: 10.1038/s41598-019-47026-6. View

19.

Antzoulatos E, Jakowec M, Petzinger G, Wood R . Sex differences in motor behavior in the MPTP mouse model of Parkinson's disease. Pharmacol Biochem Behav. 2010; 95(4):466-72. PMC: 2866026. DOI: 10.1016/j.pbb.2010.03.009. View

20.

Kent K, Charlton K, Roodenrys S, Batterham M, Potter J, Traynor V . Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia. Eur J Nutr. 2015; 56(1):333-341. DOI: 10.1007/s00394-015-1083-y. View