title: Methamphetamine induces low levels of neurogenesis in striatal neuron subpopulations and differential motor performance.
abstract: Methamphetamine (METH) causes significant loss of some striatal projection and interneurons. Recently, our group reported on the proliferation of new cells 36 h after METH and some of the new cells survive up to 12 weeks (Tulloch et al., Neuroscience 193:162-169, 2011b). We hypothesized that some of these cells will differentiate and express striatal neuronal phenotypes. To test this hypothesis, mice were injected with METH (30 mg/kg) followed by a single BrdU injection (100 mg/kg) 36 h after METH. One week after METH, a population of BrdU-positive cells expressed the neuronal progenitor markers nestin (18 %) and β-III-tubulin (30 %). At 8 weeks, 14 % of the BrdU-positive cells were also positive for the mature neuron marker, NeuN. At 12 weeks, approximately 7 % of the BrdU-positive cells co-labeled with ChAT, PV or DARPP-32. We measured motor coordination on the rotarod and psychomotor activity in the open-field. At 12 weeks, METH-injected mice exhibited delayed motor coordination deficits. In contrast, open-field tests revealed that METH-injected mice compared to saline mice displayed psychomotor deficits at 2.5 days but not at 2 or more weeks after METH. Taken together, these data demonstrate that some of the new cells generated in the striatum differentiate and express the phenotypes of striatal neurons. However, the proportion of these new neurons is low compared to the proportion that died by apoptosis 24 h after the METH injection. More studies are needed to determine if the new neurons are functional.
authors.affiliation: Department of Biological Sciences, Hunter College, 695 Park Avenue, New York, NY, 10065, USA.
authors.forename: I K
authors.initials: IK
authors.lastname: Tulloch
authors.forename: L
authors.initials: L
authors.lastname: Afanador
authors.forename: L
authors.initials: L
authors.lastname: Baker
authors.forename: D
authors.initials: D
authors.lastname: Ordonez
authors.forename: H
authors.initials: H
authors.lastname: Payne
authors.forename: I
authors.initials: I
authors.lastname: Mexhitaj
authors.forename: E
authors.initials: E
authors.lastname: Olivares
authors.forename: A
authors.initials: A
authors.lastname: Chowdhury
authors.forename: J A
authors.initials: JA
authors.lastname: Angulo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D010320:Parvalbumins; C497929:Ppp1r1b protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; D008694:Methamphetamine; D002795:Choline O-Acetyltransferase