Does MPTP Cause Apoptosis and/or Necrosis?
Not only are many of the theories on the mechanism of action of MPTP highly reflective of current theories on PD, but also, so are many of the controversies. Nowhere has this been more evident than when it comes to determining the role of apoptosis in cell death. This possibility was raised by Mochizuki and colleagues (244) when they reported morphologic and histochemical evidence of apoptotic cell death in mesencephalic-striatal co-cultures exposed to MPTP. However, a year later, using an acute dose in vivo paradigm in mice, Jackson-Lewis and colleagues (245) failed to find any evidence of apoptosis (although, interestingly, they did note that MPTP can induce a loss of TH immunoreactivity without causing neuronal degeneration, an important caveat for anyone working in the field). Subsequent studies, however, have found evidence of apoptosis, including experiments involving the exposure of PC12 cells in tissue culture to the 2′-ethylphenyl analog of MPTP (246), SH-SY5Y human neuroblast