Neuropeptide Y Protects against Methamphetamine-Induced Neuronal Apoptosis in the Mouse Striatum

Thiriet, Nathalie; Deng, Xiaolin; Solinas, Marcello; Ladenheim, Bruce; Curtis, Wendy; Goldberg, Steven R.; Palmiter, Richard D.; Cadet, Jean Lud

doi:10.1523/jneurosci.4893-04.2005

Cited by 83 publications

(90 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, SST attenuated NMDA-induced cell death in cultured fetal rat cortical neurons (Forloni et al, 1997). In addition, a recent study showed that the intraventricular administration of the neuropeptide NPY protected the mouse striatum from METH-induced apoptosis (Thiriet et al, 2005). These studies suggest that SST and NPY belong to a class of neuroprotective peptides in the brain.…”

Section: Discussionmentioning

confidence: 87%

Methamphetamine-induced cell death: Selective vulnerability in neuronal subpopulations of the striatum in mice

2006

View full text Add to dashboard Cite

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 M r 32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH induces apoptosis in approximately 21% of dopamine-and cAMP-regulated phosphoprotein, of apparent M r 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 GABAparvalbumin 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. Keywords methamphetamine; apoptosis; striatum; projection neurons; interneurons Methamphetamine (METH) is a potent and addictive psychostimulant. The neurotoxic effects of this substituted amphetamine are associated with its ability to induce an overflow of dopamine in the synapse by displacing vesicular dopamine stores (Raiteri et al., 1979; Liang and Rutledge, 1982a,b;Schmidt et al., 1985;Sulzer et al., 1995). Displaced dopamine molecules and its metabolites can be readily oxidized to reactive quinones and semiquinones (Cadet and Brannock, 1998) and nitrogen radicals (Lipton and Rosenberg, 1994;Imam et al., 1999) that affect a wide range of modifications of proteins, sugars, and lipids. Augmented levels of dopamine in the synapse induced by METH have been shown in humans (Wilson et al., 1996;McCann et al., 1998), non-human primates (Seiden et al., 1976;Villemagne et al., 1998;Harvey e...

show abstract

Section: Discussionmentioning

confidence: 87%

Methamphetamine-induced cell death: Selective vulnerability in neuronal subpopulations of the striatum in mice

2006

View full text Add to dashboard Cite

show abstract

“…Striatum (including caudate and accumbens nuclei) were isolated by freehand dissection as previously performed (Thiriet et al, 2005), immediately frozen on dry ice and stored at −80 °C until use. RNAs were isolated using RNeasy Mini kit (Qiagen).…”

Section: Tissue and Rna Preparationmentioning

confidence: 99%

“…2 kinases involved in cell signalling (PKC lambda and MAP3K12); decorin (DEC) a gene involved in cellular architecture, Proteasome 26S subunit, non-ATPase 4 (PSMD4) a gene involved in transcription and translation and a member of the dynamin family, Dynamin 1-like (DNM1L),which is involved in several processes including budding of transport vesicles, division of organelles, cytokinesis and pathogen resistance (Praefcke and McMahon, 2004). Total RNA previously extracted from striatum (n=8) was reversetranscribed using the Superscript II reverse transcriptase (Invitrogen) (Thiriet et al, 2005(Thiriet et al, , 2002. PCR experiments were then performed using LightCycler technology and the DyNAmo™ Capillary SYBR® Green qPCR kit (Ozyme, France).…”

Section: Real-time Reverse Transcription-polymerase Chain Reaction (Rmentioning

confidence: 99%

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

et al. 2008

View full text Add to dashboard Cite

We have previously shown that environmental enrichment decreases the activating and rewarding effects of the psych psychostimulant cocaine and increases resistance to the neurotoxic effect of the Parkinson-inducing drug MPTP. These effects were accompanied by an increase in the striatal expression of the neurotrophin BDNF, an increase in the striatal levels of delta-Fos B and by a decrease in striatal levels of the dopamine transporter, the main molecular target for cocaine and MPTP. Here, we used cDNA arrays to investigate the effects of rearing mice in enriched environments from weaning to adulthood on the profile of expression of genes in the striatum focusing on genes involved in intracellular signalling and functioning. We found that mice reared in an enriched environment show several alterations in the levels of mRNA coding for proteins involved in cell proliferation, cell differentiation, signal transduction, transcription and translation, cell structure and meta metabolism. Several of these findings were further confirmed by real-time quantitative PCR and, in the case of protein kinase C lambda, also by western blot. These findings are the first description of alterations in striatal gene expression by an enriched environment. The striatal gene expression regulation by environment that we report here may play a role in the resistance to the effects of drugs of abuse and dopaminergic neurotoxins previously reported.

show abstract

“…The neurotoxic effects are evidenced by long-term depletions in striatal dopamine (DA) and serotonin (5-HT) concentrations, and their uptake sites (Friedman et al, 1998;Ricaurte et al, 1982;Wagner et al, 1980), decreases in tryptophan and tyrosine hydroxylase activity (Bakhit et al, 1981), and cell loss (Deng et al, 2007;Sonsalla et al, 1996;Thiriet et al, 2005;Yu et al, 2004;Zhu et al, 2006). In addition to the hypotheses of oxidative stress and apoptosis as mechanisms of METH-induced neurotoxicity (for review, see Davidson et al, 2001;Kita et al, 2003;Quinton and Yamamoto, 2006), increases in the extracellular concentrations of glutamate (GLU) have been also suggested to play an important role (Abekawa et al, 1994;Nash and Yamamoto, 1992;Sonsalla et al, 1989;Stephans and Yamamoto, 1994).…”

Section: Introductionmentioning

confidence: 99%

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Tata

Yamamoto

2008

Synapse

View full text Add to dashboard Cite

Striking parallels exist between the neurochemical and toxic effects of stress and methamphetamine. Despite these similarities, no studies have examined how stress may promote the toxic effects of methamphetamine (METH). The current study tested the hypothesis that chronic stress enhances METH toxicity by augmenting glutamate (GLU) release and excitotoxicity in response to METH administration. Adult male Sprague-Dawley rats were exposed to 10 days of unpredictable stress and then received either saline or METH (7.5 mg/kg, i.p., once every 2 h × four injections). Prior exposure to unpredictable stress acutely enhanced the striatal extracellular GLU concentrations in response to METH, and eventually caused proteolysis of the cytoskeleton protein spectrin. Administration of the corticosterone synthesis inhibitor, metyrapone (25 mg/kg, i.p., prior to each stressor), during unpredictable stress attenuated the enhanced striatal GLU release in response to METH, blocked spectrin proteolysis, and attenuated METH-associated toxicity measured by long-term depletions in the dopamine and serotonin tissue content as well as depletions in dopamine and serotonin transporter immunoreactivity of the striatum. In summary, prior exposure to unpredictable stress enhances METH-induced elevations of GLU in the striatum, resulting in long-term excitotoxic damage and an augmentation of damage to dopamine and serotonin terminals. These studies provide a neurochemical basis for how stress contributes to the deleterious effects of METH abuse.

show abstract

Neuropeptide Y Protects against Methamphetamine-Induced Neuronal Apoptosis in the Mouse Striatum

Cited by 83 publications

References 53 publications

Methamphetamine-induced cell death: Selective vulnerability in neuronal subpopulations of the striatum in mice

Methamphetamine-induced cell death: Selective vulnerability in neuronal subpopulations of the striatum in mice

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Contact Info

Product

Resources

About