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.
journal_name
Front Neuroljournal_title
Frontiers in neurologyauthors
Cisneros IE,Ghorpade A,Borgmann Kdoi
10.3389/fneur.2020.593146subject
Has Abstractpub_date
2020-11-25 00:00:00pages
593146issn
1664-2295journal_volume
11pub_type
杂志文章abstract::Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are major contributors to morbidity and mortality. Following the initial insult, patients may deteriorate due to secondary brain damage. The underlying molecular and cellular cascades incorporate components of the innate immune system. There are different ...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00351
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abstract::Introduction: The recent publication of a trial failed to prove the efficacy of minimally invasive surgery (MIS) in patients with intracerebral hemorrhage. The aim of this study was to answer the question: Do we need more trials to compare MIS vs. conservative treatment in these patients? Methods: Databases were searc...
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doi:10.3389/fneur.2020.00426
更新日期:2020-06-04 00:00:00
abstract::Inconsistent gender differences in the outcome of TBI have been reported. The mechanism is unknown. In a recent male animal study, repeated stress followed by TBI had synergistic effects on brain gene expression and caused greater behavioral deficits. Because females are more likely to develop anxiety after stress and...
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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abstract::Background: Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor. Carmustine is used by intravenous injection or local implantation in the resection cavity for gliomas, including GBMs. However, the therapeutic potential of carmustine is not well-recognized. This analysis aimed to evaluate th...
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doi:10.3389/fneur.2020.01036
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abstract::In order to better understand how to identify and treat student-athletes who experience concussions, better insight into reporting behavior of athletes is needed. This study aims to identify information influencing athletes' attitudes toward reporting their concussions and the perceived trajectory of their recovery bo...
journal_title:Frontiers in neurology
pub_type: 杂志文章
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journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00396
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abstract::Objective: To investigate the dynamic amplitude of low-frequency fluctuations (dALFFs) in patients with Parkinson's disease (PD) and healthy controls (HCs) and further explore whether dALFF can be used to test the feasibility of differentiating PD from HCs. Methods: Twenty-eight patients with PD and 28 demographically...
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pub_type: 杂志文章
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更新日期:2019-10-01 00:00:00
abstract:Background:Disparities in outcome after intracerebral hemorrhage (ICH) among Asians, Native Hawaiians, and other Pacific Islanders (NHOPI) have been inadequately studied. We sought to assess differences in functional outcome between Asians and NHOPI after ICH. Methods:A multiracial prospective cohort study of ICH pati...
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pub_type: 杂志文章
doi:10.3389/fneur.2018.00186
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.3389/fneur.2015.00062
更新日期:2015-03-23 00:00:00
abstract::Background: Electrical Status Epilepticus in Sleep (ESES) is an epileptic encephalopathy syndrome characterized by infrequent clinical seizures and prominent interictal burden during slow wave sleep associated with cognitive deficits and behavioral dysfunction. Medical treatment with anti-epileptic drugs is often unsu...
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pub_type: 杂志文章
doi:10.3389/fneur.2019.01397
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journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.605696
更新日期:2021-01-06 00:00:00
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journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00819
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journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2016.00113
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journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00160
更新日期:2012-11-08 00:00:00
abstract::[This corrects the article DOI: 10.3389/fneur.2020.578924.]. ...
journal_title:Frontiers in neurology
pub_type: 已发布勘误
doi:10.3389/fneur.2020.638735
更新日期:2021-01-12 00:00:00
abstract::Background: Matrix metalloproteinases (MMPs) are pleiotropic enzymes involved in extracellular protein degradation and turnover. MMPs are implicated in the pathogenesis of many neurological diseases, including multiple sclerosis (MS). Objective: To search the level of MMPs in the cerebrospinal fluid (CSF) of MS patien...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.01080
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pub_type: 杂志文章
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pub_type: 杂志文章
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doi:10.3389/fneur.2018.00522
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journal_title:Frontiers in neurology
pub_type:
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pub_type: 杂志文章
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更新日期:2018-03-06 00:00:00
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pub_type: 杂志文章,评审
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