Neuropeptide Y protects against methamphetamine-induced neuronal apoptosis in the mouse striatum.
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.
Thiriet
Nathalie
N
Centre National de la Recherche Scientifique 6187, University of Poitiers, 86000 Poitiers, France.
Deng
Xiaolin
X
Solinas
Marcello
M
Ladenheim
Bruce
B
Curtis
Wendy
W
Goldberg
Steven R
SR
Palmiter
Richard D
RD
Cadet
Jean Lud
JL
D000818:Animals; D017209:Apoptosis; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004745:Enkephalins / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced; D013287:Illicit Drugs / Q000633:toxicity*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis / Q000502:physiology
D004745:Enkephalins; D013287:Illicit Drugs; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D008694:Methamphetamine; D019001:Nitric Oxide Synthase