Microglial and astrocytic changes in the striatum of methamphetamine abusers

Kitamura, Osamu; Takeichi, Toshiaki; Wang, Elaine Lu; Tokunaga, Itsuo; Ishigami, Akiko; Kubo, Shin‐ichi

doi:10.1016/j.legalmed.2009.11.001

Cited by 72 publications

(53 citation statements)

References 42 publications

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“…For example, human imaging studies show reduced hippocampal volume, particularly gray matter volume, and decreased hippocampal responsiveness in chronic methamphetamine users (Thompson et al, 2004, Kim et al, 2010, Schwartz et al, 2010, Daumann et al, 2011, Nakama et al, 2011, Orikabe et al, 2011, Morales et al, 2012), indicating maladaptive hippocampal networking in methamphetamine-exposed individuals. Postmortem analyses in human brain tissue confirms that chronic methamphetamine use produces neurotoxicity in the hippocampus (Kitamura, 2009, Kitamura et al, 2010), which suggests an association between hippocampal dysfunction and toxicity in methamphetamine addicts.…”

Section: Introductionmentioning

confidence: 78%

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

2015

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Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in hippocampal subregions that may contribute to the altered synaptic activity in the hippocampus, which may underlie enhanced negative affective symptoms and perpetuation of the addiction cycle.

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Section: Introductionmentioning

confidence: 78%

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

2015

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“…These findings suggest that some of the pathological changes in certain brain regions might be reversible and have gradually diminished following extended abstinence from Meth (Volkow et al 2001; Wang et al 2004; Nordahl et al 2005; Sekine et al 2008; Salo et al 2011; Yang et al 2015). It is also possible that some of the brain pathological changes examined in this study (Soontornniyomkij et al 2016) might not have been induced by Meth in the first place (Kitamura et al 2010; Tong et al 2014). It is possible that susceptibility to Meth neurotoxicity might vary from region to region in the CNS (Wang et al 2004; Kuhn et al 2011).…”

Section: Neuropathologymentioning

confidence: 96%

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

Soontornniyomkij

Kesby

Morgan

et al. 2016

J Neuroimmune Pharmacol

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Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.

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“…Recent studies have suggested that METH is a neurotoxic drug that can cause pathological changes and death in neuronal and glial cells (Thompson et al, 2004;Kitamura et al, 2007Kitamura et al, , 2010Takeichi et al, 2012). METH induces glial cell hyperactivity and death via many pathways, including apoptosis, oxidative stress, inflammation, interruption of mitochondrial function, and endoplasmic reticulum (ER)-stress responses (Tocharus et al, 2010;Jumnongprakhon et al, 2014Jumnongprakhon et al, , 2015Shah and Kumar, 2016).…”

Section: Introductionmentioning

confidence: 99%

Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines

et al. 2017

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-Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood. This study investigated the protective effect of melatonin against METH toxicity-mediated ER stress in glial cells. Our study demonstrated that METH increased glial cell toxicity related to METH-induced ER stress by stimulating the unfolded protein response (UPR) to activate the expression of ER stress transducers, including phosphorylated doublestranded RNA-activated protein kinase (PKR)-like ER kinase (p-PERK), activating transcription factor (ATF6), and phosphorylated inositol-requiring enzyme 1 (p-IRE1). Moreover, the expression of binding immunoglobulin protein (Bip), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, phosphorylated eukaryotic translation initiation factor 2 alpha (p-eIF2α) and spliced X-box-binding protein-1 (XBP-1) mRNA were also increased. Melatonin reduced ER stress induced by METH toxicity by reducing the expression of ER stress response genes and proteins in a concentration-dependent manner. In addition, melatonin promoted the expression of Bip chaperone in a concentration-dependent manner. Taken together, our findings suggest that melatonin can protect against ER stress-induced glial cell death induced by METH.

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Microglial and astrocytic changes in the striatum of methamphetamine abusers

Cited by 72 publications

References 42 publications

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines

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