Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson's disease.
Emerging evidence suggests beneficial effects of estrogen and estrogen-like chemicals on neurodegenerative diseases, especially Parkinson's disease (PD). Genistein, an isoflavone naturally found in soy products, displays estrogenic properties. The present study aims to investigate the neuroprotective effects of genistein on dopaminergic neurons in ovariectomized (OVX), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. MPTP significantly decreased the levels of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, which could be restored by genistein or estrogen pretreatment. MPTP-challenge with genistein or estrogen pretreatment demonstrated reduced neurotoxicity, with tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra pars compacta (SNpc) affected to a significantly lesser extent as compared to the MPTP treated control. The reverse transcription-PCR results also confirmed that the MPTP-induced downregulation of TH, dopamine transporter (DAT) and Bcl-2 mRNA expression in the midbrain could be restored by genistein or estrogen pretreatment. These findings provide the first evidence that genistein has neuroprotective effects on dopaminergic neurons in the MPTP-induced PD mice and this effect may be attributed to enhancing Bcl-2 gene expression.
Liu
Li-Xing
LX
Department of Physiology, Medical College of Qingdao University, PR China.
Chen
Wen-Fang
WF
Xie
Jun-Xia
JX
Wong
Man-Sau
MS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000737:chemistry / Q000627:therapeutic use*; D006719:Homovanillic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D010052:Ovariectomy; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013378:Substantia Nigra / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D015102:3,4-Dihydroxyphenylacetic Acid; D004958:Estradiol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019833:Genistein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid