PMID- 16650608
OWN - NLM
STAT- MEDLINE
DCOM- 20060925
LR  - 20211020
IS  - 0306-4522 (Print)
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 140
IP  - 2
DP  - 2006 Jun 30
TI  - Methamphetamine-induced cell death: selective vulnerability in neuronal 
      subpopulations of the striatum in mice.
PG  - 607-22
AB  - Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an 
      indirect dopamine agonist. In the striatum, METH has been shown to cause long 
      lasting neurotoxic damage to dopaminergic nerve terminals and recently, the 
      degeneration and death of striatal cells. The present study was undertaken to 
      identify the type of striatal neurons that undergo apoptosis after METH. Male 
      mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h 
      later. To demonstrate that METH induces apoptosis in neurons, we combined 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining with immunohistofluorescence for the neuronal marker neuron-specific 
      nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout 
      the striatum. METH induces apoptosis in approximately 25% of striatal neurons. 
      Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial, 
      dorsolateral and ventrolateral quadrants of the striatum did not reveal 
      anatomical preference. The type of striatal neuron undergoing cell death was 
      determined by combining TUNEL with immunohistofluorescence for selective markers 
      of striatal neurons: dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 
      32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH 
      induces apoptosis in approximately 21% of dopamine- and cAMP-regulated 
      phosphoprotein, of apparent Mr 32,000-positive neurons (projection neurons), 45% 
      of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of 
      cholinergic neurons in the dorsal-medial striatum. In contrast, the SST-positive 
      interneurons were refractory to METH-induced apoptosis. Finally, the amount of 
      cell loss determined with Nissl staining correlated with the amount of TUNEL 
      staining in the striatum of METH-treated animals. In conclusion, some of the 
      striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons 
      were removed by apoptosis in the aftermath of METH. This imbalance in the 
      populations of striatal neurons may lead to functional abnormalities in the 
      output and processing of neural information in this part of the brain.
FAU - Zhu, J P Q
AU  - Zhu JP
AD  - Department of Biological Sciences, Hunter College of the City University of New 
      York, 695 Park Avenue, New York, NY 10021, USA.
FAU - Xu, W
AU  - Xu W
FAU - Angulo, J A
AU  - Angulo JA
LA  - eng
GR  - R01 DA020142/DA/NIDA NIH HHS/United States
GR  - R01 DA020142-02/DA/NIDA NIH HHS/United States
GR  - G12 MD007599/MD/NIMHD NIH HHS/United States
GR  - NS41073/NS/NINDS NIH HHS/United States
GR  - U54 NS041073/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060502
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Biomarkers)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (NeuN protein, mouse)
RN  - 0 (Neurotoxins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Nuclear Proteins)
RN  - 44RAL3456C (Methamphetamine)
SB  - IM
MH  - Amphetamine-Related Disorders/*pathology/physiopathology
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Biomarkers/metabolism
MH  - Central Nervous System Stimulants/toxicity
MH  - Corpus Striatum/*drug effects/metabolism/pathology
MH  - DNA-Binding Proteins
MH  - Disease Models, Animal
MH  - Drug Resistance/physiology
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Interneurons/drug effects/metabolism/pathology
MH  - Male
MH  - Methamphetamine/*toxicity
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Nerve Degeneration/*chemically induced/pathology/physiopathology
MH  - Nerve Tissue Proteins/drug effects/metabolism
MH  - Neural Pathways/drug effects/pathology
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Neurotoxins/*toxicity
MH  - Neurotransmitter Agents/metabolism
MH  - Nuclear Proteins/metabolism
PMC - PMC2882192
MID - NIHMS208349
EDAT- 2006/05/03 09:00
MHDA- 2006/09/26 09:00
PMCR- 2010/06/08
CRDT- 2006/05/03 09:00
PHST- 2005/08/14 00:00 [received]
PHST- 2006/02/02 00:00 [revised]
PHST- 2006/02/08 00:00 [accepted]
PHST- 2006/05/03 09:00 [pubmed]
PHST- 2006/09/26 09:00 [medline]
PHST- 2006/05/03 09:00 [entrez]
PHST- 2010/06/08 00:00 [pmc-release]
AID - S0306-4522(06)00210-7 [pii]
AID - 10.1016/j.neuroscience.2006.02.055 [doi]
PST - ppublish
SO  - Neuroscience. 2006 Jun 30;140(2):607-22. doi: 10.1016/j.neuroscience.2006.02.055. 
      Epub 2006 May 2.