While evidence has pointed to β-amyloid precursor proteins (APP) as a factor involved in the pathogenesis of Alzheimer's disease (AD), recent studies have demonstrated that APP is neuroprotective in function. Our observations have also indicated an increase of APP in retinal neurons and Müller glia following axotomy, ischemia and excitatory insults. In this study, we investigate further the effect of 1-methyl-4-phenyl-pyridinium (MPP+), a neurotoxic metabolite that selectively damages dopaminergic neurons and is considered to be a parkinsonism inducer, on the expression of APP- and AD-associated proteins in relation to neuronal death and glial response. One hour to 2 months after unilateral injection of MPP+ (100 nmol) to the striatum in the rat, a significant increase in APP expression was observed in damaged regions and remote areas including the ipsilateral cortex, whereas no detectable changes were observed in the contralateral side of the brain. The immunoreactive pattern and time-dependent increase of AD associated proteins, i.e., tau, apolipoprotein E and presenilins, was similar to that of APP in the severely injured striatum and cortex. A colocalization of these proteins and OX-42-positive cells, a marker of microglia and macrophages, was observed as well. Although the number of dopaminergic neurons decreased significantly in the substantia nigra, presumably by retrograde degeneration, the immunoreactivities of AD-related gene products were not altered obviously in this area. Other AD-related gene products such as β-amyloid showed no detectable changes in the nigrostriatal pathway at any time after MPP+ intoxication. These observations suggest that APP and several gene products are molecular markers of injured neurons and are capable of providing certain signals to neuronal survival or/and death, and that glial cells take part in producing abnormal amount of AD-associated proteins which may have pathological implications, and indirectly correlate with a parkinsonian condition.
All Science Journal Classification (ASJC) codes
- 生物化學、遺傳與分子生物學 (全部)