ABSTRACT
AIM: This study was designed to investigate the anti-inflammatory effects of bee venom (BV) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). METHOD: MPTP was administered by intraperitoneal (IP) injection at 2-hr intervals over an 8-hr period. Mice were then subjected to BV subcutaneous injection and sacrificed on days 1 and 3 following the final MPTP injection. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) was assessed by tyrosine hydroxylase (TH) immunohistochemistry. Microglial activation was measured by immunohistochemistry for macrophage antigen complex-1 (MAC-1) and inducible nitric oxide synthase (iNOS). The staining intensities of MAC-1 and iNOS were quantified with respect to optical density. RESULT: In animals treated with MPTP, the survival percentages of TH+ cells in the SNpc were 32% on day 1 and 46% on day 3 compared with normal mice. In BV-treated mice, the survival percentages of TH+ cells improved to 70% on day 1 and 78% on day 3 compared with normal mice. BV treatment also resulted in reduced expression of the inflammation markers MAC-1 and iNOS in the SNpc. CONCLUSION: These data suggest that BV injection may have a neuroprotective effect that attenuates the activation of the microglial response, which has implications for the treatment of PD.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Bee Venoms/therapeutic use , Inflammation Mediators/antagonists & inhibitors , Neurons/pathology , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/pathology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/antagonists & inhibitors , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Bee Venoms/administration & dosage , Cell Death/drug effects , Cell Death/physiology , Disease Models, Animal , Dopamine Antagonists/administration & dosage , Dopamine Antagonists/therapeutic use , Inflammation Mediators/adverse effects , Male , Mice , Mice, Inbred C57BL , Neurons/drug effects , Neurons/enzymology , Neuroprotective Agents/therapeutic use , Random Allocation , Substantia Nigra/drug effects , Substantia Nigra/enzymology , Substantia Nigra/pathology , Tyrosine 3-Monooxygenase/biosynthesis , Tyrosine 3-Monooxygenase/physiologyABSTRACT
Apoptosis has been implicated in the pathogenesis of neurodegenerative diseases such as stroke and Alzheimer's disease. Apo-1/Fas gene is one of the mediators of apoptosis in stroke. Mval polymorphism is the first polymorphic marker identified in the Apo-1/Fas gene promoter, which was typed by PCR and followed by Mval digestion and gel electrophoresis. DNA isolated from peripheral blood collected from 91 stroke patients and 103 healthy blood donors was used for genotypes of GG, GA and AA by sequence specific primer PCR. Mval polymorphism was examined based on Fas gene promotor region by restriction fragment length polymorphism (RFLP). The Fas-GG genotype was the least frequent in patients with stroke and healthy controls (P = 0.57). In normal Korean controls the Mval polymorphism GA, AA and GG were 48.6%, 34.9% and 16.5%. In stroke patients were 56.2%, 29.6% and 14.2% respectively. And the allelic frequencies of Mval*2 (G) allele were less frequent than Mval*1 (A) allele in patients with stroke and healthy controls (P = 0.76). In normal Korean controls Mval*1 (A) and Mval*2 (G) alleles were 59.2% and 40.8%. In stroke patients were 57.6% and 42.4%, respectively. Our results, pending confirmation in a larger study, indicate that the Fas genotype may not appear to be a risk factor for stroke in Korean stroke patients.
