Decrease of aquaporin-4 and excitatory amino acid transporter-2 indicate astrocyte dysfunction for pathogenesis of cortical degeneration in HIV-associated neurocognitive disorders

2016 ◽  
Vol 37 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Hui Qin Xing ◽  
Yu Zhang ◽  
Kimiko Izumo ◽  
Shiho Arishima ◽  
Ryuji Kubota ◽  
...  
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporter ◽  
Neurocognitive Disorders ◽  
Aquaporin 4 ◽  
Excitatory Amino Acid Transporter ◽  
Acid Transporter ◽  
Hiv Associated Neurocognitive Disorders

scholarly journals Methamphetamine Activates Trace Amine Associated Receptor 1 to Regulate Astrocyte Excitatory Amino Acid Transporter-2 via Differential CREB Phosphorylation During HIV-Associated Neurocognitive Disorders

2020 ◽  
Vol 11 ◽  
Author(s):  
Irma E. Cisneros ◽  
Anuja Ghorpade ◽  
Kathleen Borgmann
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Second Messengers ◽  
Amino Acid Transporter ◽  
Neurocognitive Disorders ◽  
Excitatory Amino Acid Transporter ◽  
Creb Phosphorylation ◽  
Creb Activation ◽  
Trace Amine ◽  
Hiv Associated Neurocognitive Disorders

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.

5′-Heterogeneity of the human excitatory amino acid transporter cDNA EAAT2 (GLT-1)

Neuroreport ◽  
1998 ◽  
Vol 9 (7) ◽  
pp. 1295-1297 ◽  
Author(s):  
Christoph Münch ◽  
Birgit Schwalenstöcker ◽  
Birgit Knappenberger ◽  
Stephan Liebau ◽  
Helge Völkel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporter ◽  
Excitatory Amino Acid Transporter ◽  
Acid Transporter
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