title: Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of nigral dopaminergic neurons and a reduction in striatal dopaminergic fibers, which result in tremors, rigidity, bradykinesia and gait disturbance. In addition to motor dysfunction, dementia is a widely recognized symptom of patients with PD. Berberine, an isoquinoline alkaloid isolated from Berberis vulgaris L., is known to exert anxiolytic, analgesic, anti-inflammatory, antipsychotic, antidepressant and anti-amnesic effects. In the present study, we investigated the effects of berberine on short-term memory in relation to dopamine depletion and hippocampal neurogenesis using a mouse model of PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) treatment. Mice in the berberine-treated groups were orally administered berberine once a day for a total of 5 weeks. Our results revealed that the injection of MPTP/P induced dopaminergic neuronal death in the substantia nigra and fiber loss in the striatum. This resulted in impaired motor balance and coordination, as assessed by the beam walking test. We further demonstrated that MPTP/P-induced apoptosis in the hippocampus deteriorated short-term memory, as shown by the step-down avoidance task. By contrast, neurogenesis in the hippocampal dentate gyrus, which is a compensatory adaptive response to excessive apoptosis, was increased upon PD induction. However, treatment with berberine enhanced motor balance and coordination by preventing dopaminergic neuronal damage. Treatment with berberine also improved short-term memory by inhibiting apoptosis in the hippocampus. Berberine demonstrated maximal potency at 50 mg/kg. Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with PD.
authors.affiliation: Department of Cardiovascular and Neurologic Diseases (Stroke Center), College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Mia
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Cardiovascular and Neurologic Diseases (Stroke Center), College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Mal-Soon
authors.initials: MS
authors.lastname: Shin
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Han-Sam
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Food and Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-721, Republic of Korea.
authors.forename: Hyeon Jeong
authors.initials: HJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D001599:Berberine; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3