en بیولوژی سلولی- مولکولی Cellular and Molecular Biology پژوهشي Original Research <strong>Background</strong>: Parkinson&rsquo;s disease (PD) is a neurodegenerative disorder marked by dopaminergic neuron loss, oxidative stress, and neuroinflammation, leading to progressive motor dysfunction. Current treatments provide symptomatic relief but do not halt disease progression. Caffeine, a widely consumed neurostimulant, has been linked to a reduced risk of PD and possesses antioxidant and anti-inflammatory properties.&nbsp;<br> <strong>Objectives</strong>: We investigated the effects of caffeine on motor performance, biochemical markers, and immunohistochemical changes in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced model of PD in female Swiss mice.&nbsp;<br> <strong>Methods</strong>: Twenty-five female mice were used, with 20 injected intraperitoneally (ip) with MPTP to induce PD. The mice were divided into five groups (n=5): Healthy controls, MPTP-induced PD, L-Dopa, 10 mg/kg caffeine, and 5 mg/kg caffeine for three weeks. Behavioral tests, including the pole test, beam test, and open field maze assessed motor activity and anxiety. Brain, liver, and heart tissues were analyzed for antioxidant, inflammatory, and oxidative stress markers. Brain tissues were also examined for immunohistochemistry, assessing microglial activation, TH, and &alpha;-synuclein to measure dopamine loss.&nbsp;<br> <strong>Results</strong>: Caffeine administration significantly (P<0.05) improved motor performance and decreased anxiety compared to MPTP-induced mice. Biochemical analyses of brain tissue showed that caffeine enhanced antioxidant activity by increasing the levels of catalase and glutathione while decreasing malondialdehyde (MDA), a marker of oxidative stress. Caffeine also significantly reduced the levels of pro-inflammatory cytokines, TNF-&alpha;, and IL-1&alpha; in the brain tissue, indicating an anti-inflammatory effect. Serum biochemical analyses indicated increased superoxide dismutase (SOD) levels, elevated catalase activity, and reduced MDA levels in caffeine-treated groups. Immunohistochemical analysis revealed a significant reduction in the expression of &alpha;-synuclein and microglial activation and preservation of TH-positive dopaminergic neurons in the substantia nigra following caffeine treatment.&nbsp;<br> <strong>Conclusion</strong>: Caffeine exerts protective effects against motor dysfunction, oxidative stress, and neuroinflammation in an MPTP-induced model of PD, highlighting its potential as a therapeutic agent for managing PD.&nbsp; Caffeine, Parkinson’s disease (PD), Neuroprotection, Oxidative stress, Neuroinflammation 125 138 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-1251-1&slc_lang=en&sid=1 Aminat Omolola Imam-Fulani imamfulani.ao@unilorin.edu.ng 100319475328460011407 100319475328460011407 Yes Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Abdulrahman Olanrewaju Shuaib aoshuaib@alhikmah.edu.ng 100319475328460011408 0009-0008-3221-8385 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Lateefah Omotoyosi Olajide latolajide@gmail.com 100319475328460011409 100319475328460011409 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Halimat Oluwakemi Afolabi afolabihalimat27@gmail.com 100319475328460011410 0009-0002-5871-7744 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Jerry Inyang jerprog0@gmail.com 100319475328460011411 0009-0006-7815-1337 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Oluwadamilola Onoshi Onoshi damilolaonoshi06@gmail.com 100319475328460011412 0009-0002-9107-9457 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Taofeekat Temitope Ogunsesan temitopetaofeekat@gmail.com 100319475328460011413 0009-0003-4904-4514 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Oyindamola Bisola Adekunle adeoyin97@gmail.com 100319475328460011414 0009-0007-8352-0261 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Taiwo Elijah Eso teezy577@gmail.com 100319475328460011415 0009-0008-4363-4579 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Oluwaseyi Deborah Babatunde oluwafunmilayodebbie24@gmail.com 100319475328460011416 0009-0000-0904-2328 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Edwin Ayolola Makanjuola Edwinmakanjuola@gmail.com 100319475328460011417 100319475328460011417 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Olamilekan Abdulfatai Alimi olamilekanola18@gmail.com 100319475328460011418 0009-0005-1580-8752 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Hafeez Ajibola Olorunoje hafeezolorunoje@gmail.com 100319475328460011419 0009-0008-4116-9087 No Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Kamaldeen Olalekan Sanusi sanusikamaldeen@yahoo.com 100319475328460011420 100319475328460011420 No Department of Human Physiology, Faculty of Basic Medical Sciences, Al-Hikmah University, Ilorin, Nigeria.