Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Baptista, Sofia; Lasgi, Charlène; Benstaali, Caroline; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos; Agasse, Fabienne; Silva, Ana P.

doi:10.1016/j.scr.2014.08.003

Cited by 12 publications

(9 citation statements)

References 57 publications

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“…The cells at G2/M remained nearly the same at all METH treatments. METH-induced G0/G1 inhibition was reported earlier in dentate gyrus culture 41 .…”

Section: Resultssupporting

confidence: 62%

Identification of cytotoxic markers in methamphetamine treated rat C6 astroglia-like cells

Badisa

Wiley

Randell

et al. 2019

Sci Rep

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Methamphetamine (METH) is a powerfully addictive psychostimulant that has a pronounced effect on the central nervous system (CNS). The present study aimed to assess METH toxicity in differentiated C6 astroglia-like cells through biochemical and toxicity markers with acute (1 h) and chronic (48 h) treatments. In the absence of external stimulants, cellular differentiation of neuronal morphology was achieved through reduced serum (2.5%) in the medium. The cells displayed branched neurite-like processes with extensive intercellular connections. Results indicated that acute METH treatment neither altered the cell morphology nor killed the cells, which echoed with lack of consequence on reactive oxygen species (ROS), nitric oxide (NO) or inhibition of any cell cycle phases except induction of cytoplasmic vacuoles. On the other hand, chronic treatment at 1 mM or above destroyed the neurite-like processors and decreased the cell viability that paralleled with increased levels of ROS, lipid peroxidation and lactate, depletion in glutathione (GSH) level and inhibition at G0/G1 phase of cell cycle, leading to apoptosis. Pre-treatment of cells with N-acetyl cysteine (NAC, 2.5 mM for 1 h) followed by METH co-treatment for 48 h rescued the cells completely from toxicity by decreasing ROS through increased GSH. Our results provide evidence that increased ROS and GSH depletion underlie the cytotoxic effects of METH in the cells. Since loss in neurite connections and intracellular changes can lead to psychiatric illnesses in drug users, the evidence that we show in our study suggests that these are also contributing factors for psychiatric-illnesses in METH addicts.

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“…The cells at G2/M remained nearly the same at all METH treatments. METH-induced G0/G1 inhibition was reported earlier in dentate gyrus culture 41 .…”

Section: Resultssupporting

confidence: 62%

Identification of cytotoxic markers in methamphetamine treated rat C6 astroglia-like cells

Badisa

Wiley

Randell

et al. 2019

Sci Rep

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“…The goal of the present study was to confirm the findings of decreased NPCs and neurogenesis in the hippocampus resulting from amphetamine insult reported in rodents in a higher order organism (Teuchert-Noodt et al , 2000; Hernandez-Rabaza et al , 2006; Cho et al , 2008; Mandyam et al , 2008; Schaefers et al , 2009; Venkatesan et al , 2011; Yuan et al , 2011; Baptista et al , 2014; Garcia-Cabrerizo & Garcia-Fuster, 2016). Many studies in the field have focused on understanding the effects of amphetamines on neurotransmitters and neurotransmitter induced neurotoxicity, but very few have sought to understand neurotoxicity as a function of altered neurogenesis.…”

Section: Discussionsupporting

confidence: 69%

“…In this context, METH exposure in rodents produces a hostile cellular environment in the progenitor pool (Yuan et al , 2011). For example, METH reduces net proliferation of NPCs and number of immature neurons by reducing the number of proliferating preneuronal neuroblasts (type-2a cells; (Kronenberg et al , 2003)) and increasing the number of proliferating preneuronal progenitor cells (type-3 cells; (Kronenberg et al , 2003; Yuan et al , 2011)), suggesting that a decrease in the number of progenitors and immature neurons, to a large degree, is attributable to the decrease in the ability of neuroblasts to divide and produce stable NPCs that survive as immature neurons (Teuchert-Noodt et al , 2000; Mandyam et al , 2008; Schaefers et al , 2009; Venkatesan et al , 2011; Yuan et al , 2011; Baptista et al , 2014). Parallel work in rodents demonstrates that MDMA affects net proliferation and survival of NPCs, suggesting that similar hostile cellular environment is observed in rodents after either METH or MDMA exposure (Hernandez-Rabaza et al , 2006; Cho et al , 2008; Garcia-Cabrerizo & Garcia-Fuster, 2016).…”

Section: Introductionmentioning

confidence: 99%

Chronic administration of amphetamines disturbs development of neural progenitor cells in young adult nonhuman primates

Dutta

Taffe

Mandyam

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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The detrimental effects of amphetamines on developmental stages of NPCs are limited to rodent brain and it is not known if these effects occur in nonhuman primates which are the focus of the current investigation. Young adult rhesus macaques either experienced MDMA only, a combination of amphetamines (MDMA, MDA and methamphetamine) or no amphetamines (controls) and hippocampal tissue was processed for immunohistochemical analysis.Quantitative stereological analysis showed that intermittent exposure to MDMA or the three amphetamines over 9.6 months causes >80% decrease in the number of Ki-67 cells (actively dividing NPCs) and >50% decrease in the number of NeuroD1 cells (NPCs that have attained a neuronal phenotype). Co-labeling analysis revealed distinct, actively dividing hippocampal NPCs in the subgranular zone of the dentate gyrus that were in transition from stem-like radial glia-like cells (type-1) to immature transiently amplifying neuroblasts (type-2a, type-2b, and type-3).MDMA-alone and the combination reduced the number of dividing type-1 and type-3 NPCs and cells that were not NPCs. These data indicate that amphetamines interfere with the division and migration of NPCs. Notably, the reduction in the number of NPCs and immature neurons were not associated with changes in cell death (via apoptosis) or granule cell neuron numbers, indicating that amphetamines selectively affected the generation and maturation of newly born granule cell neurons. In sum, our findings suggest that alterations in the cellular composition in the dentate gyrus during chronic exposure to amphetamines can effect neuroplasticity in the hippocampus and influence functional properties of hippocampal neurons.

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“…In addition to thermal shock, ID element activation and increased expression can be induced by inflammatory response [61], inhibition of protein synthesis [48] or DNA breakage, with the latter being known to also induce SINE retrotransposition [11]. Consequently, the increased expression of the ID element in the dentate gyrus may have occurred not only due to the thermal shock, but also due to METH-induced inflammatory response [62], DNA breakage [63,64,65] and/or inhibition of protein synthesis [66], with at least some of these elements retrotransposing within gDNA.…”

Section: Discussionmentioning

confidence: 99%

Neurotoxic Doses of Chronic Methamphetamine Trigger Retrotransposition of the Identifier Element in Rat Dorsal Dentate Gyrus

Moszczynska

Burghardt

2017

Genes

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Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was to determine whether neurotoxic doses of binge or chronic methamphetamine (METH) trigger retrotransposition of the identifier (ID) element, a member of the rat SINE family, in the dentate gyrus genomic DNA. Adult male Sprague-Dawley rats were treated with saline or high doses of binge or chronic METH and sacrificed at three different time points thereafter. DNA methylation analysis, immunohistochemistry and next-generation sequencing (NGS) were performed on the dorsal dentate gyrus samples. Binge METH triggered hypomethylation, while chronic METH triggered hypermethylation of the CpG-2 site. Both METH regimens were associated with increased intensities in poly(A)-binding protein 1 (PABP1, a SINE regulatory protein)-like immunohistochemical staining in the dentate gyrus. The amplification of several ID element sequences was significantly higher in the chronic METH group than in the control group a week after METH, and they mapped to genes coding for proteins regulating cell growth and proliferation, transcription, protein function as well as for a variety of transporters. The results suggest that chronic METH induces ID element retrotransposition in the dorsal dentate gyrus and may affect hippocampal neurogenesis.

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Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Cited by 12 publications

References 57 publications

Identification of cytotoxic markers in methamphetamine treated rat C6 astroglia-like cells

Identification of cytotoxic markers in methamphetamine treated rat C6 astroglia-like cells

Chronic administration of amphetamines disturbs development of neural progenitor cells in young adult nonhuman primates

Neurotoxic Doses of Chronic Methamphetamine Trigger Retrotransposition of the Identifier Element in Rat Dorsal Dentate Gyrus

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