RbAp48 expression and neuronal damage in the gerbil hippocampus following 5 min of transient ischemia

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta.In the present study, we investigated whether ␤-lapachone (␤-LAP), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model.␤-LAP reduced the tyrosine hydroxylase (TH)immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test.In addition, ␤-LAP protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra.Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ␤-LAP induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains.Western blot and immunohistochemical analyses indicated that ␤-LAP increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes.Moreover, ␤-LAP increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK).␤-LAP also increased the localization of p-AMPK and Nrf2 in astrocytes.Collectively, our data suggest that ␤-LAP exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.