RT Journal Article
SR Electronic
T1 Neuropeptide Y Protects against Methamphetamine-Induced Neuronal Apoptosis in the Mouse Striatum
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5273
OP 5279
DO 10.1523/JNEUROSCI.4893-04.2005
VO 25
IS 22
A1 Nathalie Thiriet
A1 Xiaolin Deng
A1 Marcello Solinas
A1 Bruce Ladenheim
A1 Wendy Curtis
A1 Steven R. Goldberg
A1 Richard D. Palmiter
A1 Jean Lud Cadet
YR 2005
UL http://www.jneurosci.org/content/25/22/5273.abstract
AB Methamphetamine (METH) is an illicit drug that causes neuronal apoptosis in the mouse striatum, in a manner similar to the neuronal loss observed in neurodegenerative diseases. In the present study, injections of METH to mice were found to cause the death of enkephalin-positive projection neurons but not the death of neuropeptide Y (NPY)/nitric oxide synthase-positive striatal interneurons. In addition, these METH injections were associated with increased expression of neuropeptide Y mRNA and changes in the expression of the NPY receptors Y1 and Y2. Administration of NPY in the cerebral ventricles blocked METH-induced apoptosis, an effect that was mediated mainly by stimulation of NPY Y2 receptors and, to a lesser extent, of NPY Y1 receptors. Finally, we also found that neuropeptide Y knock-out mice were more sensitive than wild-type mice to METH-induced neuronal apoptosis of both enkephalin- and nitric oxide synthase-containing neurons, suggesting that NPY plays a general neuroprotective role within the striatum. Together, our results demonstrate that neuropeptide Y belongs to the class of factors that maintain neuronal integrity during cellular stresses. Given the similarity between the cell death patterns induced by METH and by disorders such as Huntington's disease, our results suggest that NPY analogs might be useful therapeutic agents against some neurodegenerative processes.