The Drosophila excitatory amino acid transporters dEAAT1 and dEAAT2 are nervous-specific transmembrane proteins that mediate the high affinity uptake of L-glutamate or aspartate into cells. Here, we demonstrate by colocalization studies that both genes are expressed in discrete and partially overlapping subsets of differentiated glia and not in neurons in the embryonic central nervous system (CNS). We show that expression of these transporters is disrupted in mutant embryos deficient for the glial fate genes glial cells missing (gcm) and reversed polarity (repo). Conversely, ectopic expression of gcm in neuroblasts, which forces all nerve cells to adopt a glial fate, induces an ubiquitous expression of both EAAT genes in the nervous system. We also detected the dEAAT transcripts in the midline glia in late embryos and dEAAT2 in a few peripheral neurons in head sensory organs. Our results show that glia play a major role in excitatory amino acid transport in the Drosophila CNS and that regulated expression of the dEAAT genes contributes to generate the functional diversity of glial cells during embryonic development.
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http://dx.doi.org/10.1006/dbio.2002.0742 | DOI Listing |
J Neurodev Disord
January 2025
Rett Syndrome Research Trust, Trumbull, CT, USA.
Background: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.
Design: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.
Methods: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment.
Sci Rep
January 2025
Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.
The potential role of hydrogen sulfide (HS) in the modulation of neuropathic pain is increasingly recognized. This study investigated the therapeutic effect of intraperitoneal injection of the HS donor sodium hydrosulfide (NaHS) on neuropathic pain. Utilizing the spared nerve injury (SNI) model in mice, the research investigates the role of astrocytes and the excitatory neurotransmitter glutamate in chronic pain.
View Article and Find Full Text PDFNeuroscience
January 2025
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil. Electronic address:
L-proline is an amino acid with a unique cyclic structure, involvement in various physiological processes, such as protein synthesis, collagen production, and neurotransmission. This review explores the complex roles of proline in the central nervous system (CNS), where it contributes to both excitatory and inhibitory neurotransmission. Additionally, L-proline has distinct metabolic functions attributed to its structural properties.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2025
Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 Str, 02-106 Warsaw, Poland.
The purpose of this review was to analyse the literature regarding the correlation between the level of tryptamine, aryl hydrocarbon receptor (AHR) signalling pathway activation, and monoamine oxidase (MAO)-A and MAO-B activity in health and conditions such as neurodegenerative, neurodevelopmental, and psychiatric disorders. Tryptamine is generated through the decarboxylation of tryptophan by aromatic amino acid decarboxylase (AADC) in the central nervous system (CNS), peripheral nervous system (PNS), endocrine system, and gut bacteria. Organ-specific metabolism of tryptamine, which is mediated by different MAO isoforms, causes this trace amine to have different pharmacokinetics between the brain and periphery.
View Article and Find Full Text PDFNat Commun
January 2025
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transmembrane AMPA receptor regulatory proteins (TARPs) are claudin-like proteins that tightly regulate AMPA receptors (AMPARs) and are fundamental for excitatory neurotransmission. With cryo-electron microscopy (cryo-EM) we reconstruct the 36 kDa TARP subunit γ2 to 2.3 Å, which points to structural diversity among TARPs.
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