Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetamine
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ABSTRACT:
PROVIDER: PRJNA748416 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15202564.fastq.gz | Fastqsanger.gz | |||
| SRR15202565.fastq.gz | Fastqsanger.gz | |||
| SRR15202566.fastq.gz | Fastqsanger.gz | |||
| SRR15202567.fastq.gz | Fastqsanger.gz | |||
| SRR15202568.fastq.gz | Fastqsanger.gz |
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Project description:Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented microglia reactivity and abolished the behavioral phenotype elicited by Meth in the elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.
2021-07-22 | GSE180497 | GEO
Project description:Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.
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Project description:We used cortical
human fetal astrocytes, density 8-15000 cells/cm2 (ScienCell, San Diego, CA, USA seeded separately in Astrocyte
medium (ScienCell, San Diego, CA, USA) P0.
Methamphetamine (Sigma-Aldrich, St Louis, MO, USA) was prepared at a stock concentration of 10mM in distilled water. Methamphetamine dilutions 50 micromolar were made in Endo and Neuro/Astro/Peri media respectively and applied to the cells for 26 hrs. Further info in "Proteomic and metabolomic characterization of human neurovascular unit cells in response to methamphetamine" Herland et al Adv Biosystems 2020 [doi:10.25345/C55F3P] [dataset license: CC0 1.0 Universal (CC0 1.0)]
2020-07-21 | MSV000085795 | MassIVE
Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall “omic” response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals.
2010-10-31 | GSE16198 | GEO
Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall omic response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals. For each sample, 20 virgin male flies were used to extract the mRNA. Three replicates were produced for each treatments. Two treatments were produced (control VS 0.6% 24 h meth-fed).
2010-10-30 | E-GEOD-16198 | biostudies-arrayexpress
Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations. To study the effects of chronic METH effects on the brain
2011-11-15 | E-GEOD-33707 | biostudies-arrayexpress
Project description:We describe the effects of cocaine and methamphetamine treatment on astrocytic expression of the corticotropin releasing factor 2 receptor and the excitatory amino acid transporter 1 in the ventral midbrain. The RNA-sequencing data confirms the expression of CRF2R on astrocytes using the Aldh1l1-NuTRAP model. This allowed for astrocyte mRNA isolation and characterization, confirming CRF2R expression on ventral midbrain astrocytes.
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Project description:Methamphetamine (mAMPH) is a psychostimulant drug that increases extracellular levels of monoamines throughout the brain. It has previously been observed that a single injection of mAMPH increases immediate early gene (IEG) expression in both the striatum and cerebral cortex. Moreover, this effect is modulated by dopamine and glutamate receptors since systemic administration of dopamine or glutamate antagonists has been found to alter mAMPH-induced striatal and cortical IEG expression. However, because dopamine and glutamate receptors are found in extra-striatal as well as striatal brain regions, studies employing systemic injection of dopamine or glutamate antagonists fail to localize the effects of mAMPH-induced activation. In the present experiments, the roles of striatal dopamine and glutamate receptors in mAMPH-induced gene expression in the striatum and cerebral cortex were examined. The nuclear expression of Fos, the protein product of the IEG c-fos, was quantified in both the striatum and the cortex of animals receiving intrastriatal dopamine or glutamate antagonist administration. Intrastriatal infusion of dopamine (D1 or D2) or glutamate [N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] antagonists affected not only mAMPH-induced striatal, but also cortical, Fos expression. Overall, the effects of the antagonists occurred dose-dependently, in both the infused and non-infused hemispheres, with greater influences occurring in the infused hemisphere. Finally, unilateral intrastriatal infusion of dopamine or glutamate antagonists changed the behavior of the rats from characteristic mAMPH-induced stereotypy to rotation ipsilateral to the infusion. These results demonstrate that mAMPH's actions on striatal dopamine and glutamate receptors modulate the widespread cortical activation induced by mAMPH. It is hypothesized that dopamine release from nigrostriatal terminals modulates activity within striatal efferent pathways, thereby disinhibiting thalamo-cortical circuits. By extension, these results suggest processes through which repeated exposure to mAMPH might influence cortical function in mAMPH abusers.
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Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations.
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