ArticleFrontiers in neurology2020
Methamphetamine Activates Trace Amine Associated Receptor 1 to Regulate Astrocyte Excitatory Amino Acid Transporter-2 via Differential CREB Phosphorylation During HIV-Associated Neurocognitive Disorders.
Article in Frontiers in neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.Frontiers in immunology · 2024Pooled it
- Molecular Mechanisms of Hippocampal Synaptic Plasticity Disruption Induced by Chronic Methamphetamine Exposure: A Narrative Review.Cellular and molecular neurobiology · 2026Review
- Distinct roles of dopamine receptors in HIV latency reversal in a myeloid cell model.Frontiers in immunology · 2026Article
- Methamphetamine Induces Metallothionein 1 Expression and an Inflammatory Phenotype in Primary Human HIV-Infected Macrophages.International journal of molecular sciences · 2025Article
- Role of Glial Trace Amine Associated Receptor 1 (TAAR1) and Microbiota in Schizophrenia.Neurochemical research · 2025Review
- Retinal Angiogenesis in Methamphetamine Self-Administration Rats.Investigative ophthalmology & visual science · 2025Article
- Trace amine-associated receptor 1 (TAAR1): an emerging therapeutic target for neurodegenerative, neurodevelopmental, and neurotraumatic disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- Single-Cell RNA-Seq Uncovers Robust Glial Cell Transcriptional Changes in Methamphetamine-Administered Mice.International journal of molecular sciences · 2025Article
- HIV-1 and methamphetamine co-treatment in primary human astrocytes: TAARgeting ER/UPR dysfunction.NeuroImmune pharmacology and therapeutics · 2024Article
- Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling.Molecules (Basel, Switzerland) · 2024Article
- TAAR1 Regulates Purinergic-induced TNF Secretion from Peripheral, But Not CNS-resident, Macrophages.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- A Non-Canonical Role for IRE1α Links ER and Mitochondria as Key Regulators of Astrocyte Dysfunction: Implications in Methamphetamine use and HIV-Associated Neurocognitive Disorders.Frontiers in neuroscience · 2022Article
- Covid-19 interface with drug misuse and substance use disorders.Neuropharmacology · 2021Review
- Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Methamphetamine (METH) use, referred to as methamphetamine use disorder (MUD), results in neurocognitive decline, a characteristic shared with HIV-associated neurocognitive disorders (HAND). MUD exacerbates HAND partly through glutamate dysregulation. Astrocyte excitatory amino acid transporter (EAAT)-2 is responsible for >90% of glutamate uptake from the synaptic environment and is significantly decreased with METH and HIV-1. Our previous work demonstrated astrocyte trace amine associated receptor (TAAR) 1 to be involved in EAAT-2 regulation. Astrocyte EAAT-2 is regulated at the transcriptional level by cAMP responsive element binding (CREB) protein and NF-κB, transcription factors activated by cAMP, calcium and IL-1β. Second messengers, cAMP and calcium, are triggered by TAAR1 activation, which is upregulated by IL-1β METH-mediated increases in these second messengers and signal transduction pathways have not been shown to directly decrease astrocyte EAAT-2. We propose CREB activation serves as a master regulator of EAAT-2 transcription, downstream of METH-induced TAAR1 activation. To investigate the temporal order of events culminating in CREB activation, genetically encoded calcium indicators, GCaMP6s, were used to visualize METH-induced calcium signaling in primary human astrocytes. RNA interference and pharmacological inhibitors targeting or blocking cAMP-dependent protein kinase A and calcium/calmodulin kinase II confirmed METH-induced regulation of EAAT-2 and resultant glutamate clearance. Furthermore, we investigated METH-mediated CREB phosphorylation at both serine 133 and 142, the co-activator and co-repressor forms, respectively. Overall, this work revealed METH-induced differential CREB phosphorylation is a critical regulator for EAAT-2 function and may thus serve as a mechanistic target for the attenuation of METH-induced excitotoxicity in the context of HAND.
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