China
Africa
Explore chapters and articles related to this topic
Ayahuasca
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Wild Plants, 2020
Raquel Consul, Flávia Lucas, Maria Graça Campos
As MAO is responsible for endogenous neurotransmitter degradation, its inhibition alters, albeit indirectly, the homeostasis of the dopaminergic, adrenergic, and serotonergic systems, which is reflected in greater dopamine circulation, for example (Alsuntangled 2017). In addition to other less-studied mechanisms, the dopamine transport inhibition at high concentrations, specific inhibition of tyrosine-1A-phosphorylation regulatory kinase, as well as affinity for the imidazoline binding site contributes to this. Harmine, by way of example, also acts in the regulation of the excitatory amino acid transporter-2, as a primary mechanism of synaptic glutamate inactivation, as well as causing an inverse agonist effect at the benzodiazepine binding site on the GABAA (γ-aminobutiric acid) receptor (Hamill et al. 2018).
Maturation, Barrier Function, Aging, and Breakdown of the Blood–Brain Barrier
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Elizabeth de Lange, Ágnes Bajza, Péter Imre, Attila Csorba, László Dénes, Franciska Erdő
Glutamate transporters: The transporters, EAAT1, EAAT2, and EAAT3, at the BBB determine the levels of brain extracellular glutamate and are essential to prevent excitotoxicity (Lipton 2005), prompting the question whether changes in these transporters may contribute to glutamate excess and excitotoxicity. It has been suggested that glutamate excitotoxicity plays a role in the neurodegenerative processes in AD (Lipton 2005). Strict control l-glutamate concentration in the brain ISF is important to maintain neurotransmission and avoid excitotoxicity. The role of astrocytes in handling l-glutamate transport and metabolism is well known, however, ECs may also play an important role through mediating brain-to-blood l-glutamate efflux. These can account for high affinity concentrative uptake of l-glutamate from the brain ISF into the capillary ECs. The mechanisms in between l-glutamate uptake in the ECs and l-glutamate appearing in the blood may involve a luminal transporter for l-glutamate, metabolism of l-glutamate, and transport of metabolites, or a combination of the two (Cederberg et al. 2014).
Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
High-affinity uptake across the cell membrane is responsible for terminating the synaptic actions of glutamate. This uptake across the cell membrane is mediated by a sodium-dependent, high-affinity transporter that has been studied in synaptosomes and brain slices. It does not distinguish between l-glutamate, l-aspartate, and d-aspartate.170,174,175 This transporter, referred to as the excitatory amino acid transporter (EAAT), is present in both neurons and glial cells and has an uneven brain regional distribution consistent with a role in neurotransmission. Five subtypes of EAAT have been identified, some of which have a distinct anatomical distribution in the brain and a specific sensitivity to pharmacological agents.1 Both the neuronal and glial EAATs are believed to play an important role in terminating the action of glutamate following its release from nerve endings as was discussed previously for GABA. It is of interest that some glial cells also possess receptors for glutamate, which, when activated, lead to a transient increase in intracellular calcium (i.e., a Ca2+ wave) and which may pass from one glial cell to another and function as a form of intercellular communication.176 Molecular cloning studies have been used to study the different EAATs.58 These EAATs can transport glutamate as well as aspartate in a high-affinity sodium-dependent manner. They are believed to be responsible for the majority of the glutamate inactivation in the CNS.58 All five EAATs (EAAT1–EAAT5) have been cloned and studied in some detail. EAAT1 is expressed mainly in glial cells of the cerebellum whereas EAAT2 is expressed in astrocytes throughout the brain and EAAT3 is the main neuronal transporter throughout the brain.1,58,168 EAAT4 is found primarily in Purkinje cells of the cerebellum, and EAAT5 is found in several types of cells in the retina.58
Dopaminergic and glutamatergic biomarkers disruption in addiction and regulation by exercise: a mini review
Published in Biomarkers, 2022
Muhammad Abdullah, Li-Chung Huang, Shih-Hsien Lin, Yen Kuang Yang
Glutamate uptake is a promising strategy and a future therapeutic goal for the treatment of drug addiction and relapse due to excessive glutamate transmission (Rao et al.2015). A variety of glutamate transporters including excitatory amino acid transporters (EAATs), vesicular glutamate transporters (VGLUTs) and cystine glutamate antiporter (xCT), are responsible for the uptake and restoration of glutamate homeostasis (Rao et al.2015). Around 90% of extracellular glutamate is removed via GLT1 (EAAT2) (Anderson and Swanson 2000), which has been shown to be downregulated by a variety of addictive substances (Sari et al.2009, Spencer and Kalivas 2017). Medicinal compounds that manipulate glutamate transporters (GLT and xCT) and treat addiction-associated problems such as withdrawal complications, cue-induced cravings, and relapse, suggest that glutamate transport could be one of the effective therapeutic mechanisms for the treatment of drug addiction. Medicinal compounds including n-acetyl cystine and β-lactam antibiotics manipulate glutamate transporters either through expression upregulation or pharmacological modulation of the transport phenomenon (Sari et al.2009, McClure et al.2014, Rao et al.2015). Due to the current focus of researchers, as a therapeutic target that plays an immense role in glutamate uptake (90%), we reviewed GLT1 only, while a growing number of studies have shown that addictive substances also disrupt the expressions of other glutamate transporters (Spencer and Kalivas 2017).
Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea
Published in Journal of Neurogenetics, 2021
Meltem Cerrah Gunes, Murat Salih Gunes, Alperen Vural, Fatma Aybuga, Arslan Bayram, Keziban Korkmaz Bayram, Mehmet Ilhan Sahin, Muhammet Ensar Dogan, Sevda Yesim Ozdemir, Yusuf Ozkul
Slc1a2, which is known as an excitatory amino acid transporter 2 (Eaat2) or Glutamate transporter 1 (Glt1), encodes a membrane-bound transport protein located in the glial cells and presynaptic glutamatergic nerveendings. The excitotoxic effect of glutamate is terminated by glutamate transporters such as Eaat1 (Glast), Eaat2 (Slc1a2) (Shashidharan et al., 1994). Glutamate accumulation was shown in perilymph, which caused hearing loss to increase in mice with glutamate transporter (Glast: Eaat1) deficiency (Eaat1 mutant) after noise exposure (Hakuba et al., 2000). These results show that Glast prevents the concentration of glutamate to reach the toxic level in the perilymph after acoustic trauma. It was also reported that hippocampal neuronal damage was increased in the Slc1a2 knockout brain trauma model (Rao et al., 2001). In our study, a significant decrease in Slc1a2 gene expression was detected in Post-AT(15) group when compared to Control and Post-AT(1) groups and no improvement in OAE values may be related to the presence of neuronal damage caused by low expression of Slc1a2.
Clinical phenotype and genetic risk factors for bipolar disorder with binge eating: an update
Published in Expert Review of Neurotherapeutics, 2019
Alfredo B. Cuellar-Barboza, Stacey J. Winham, Joanna M. Biernacka, Mark A. Frye, Susan L. McElroy
Environmental factors can be explored with epigenetic studies, which quantify genomic changes in response to external influence. To our knowledge, only one study has evaluated the epigenetic effect of BE in BD. Jia and colleagues [153] compared the methylation of SLC1A2 promoter between BD patients with variable environmental influences of addiction (i.e. alcohol, nicotine, or food defined as binge eating) and healthy controls. Coded by SLC1A2, the excitatory amino acid transporter 2 (EAAT2) is the main transporter removing glutamate from the synapse, and its activity has been shown to be altered in BD. In this investigation, the authors found the SLC1A2 promoter region to be hypermethylated in BD alone, but it was hypomethylated in BD with nicotine addiction (p = 0.0009) and BE behavior (p = 0.0002). This finding suggests that certain behaviors such as BE may produce epigenetic changes that are either compensatory to other epigenetic modifications or preserve aberrant behaviors [153]. However, the methodology of this study had important limitations, including those inherent to its cross-sectional design, small sample size, and lack of independent replication. Further steps required to expand upon these findings would include conducting studies with longitudinal designs, replication in brain tissue, more comprehensive exploration of the genome, and establishing a strictly refined phenotype to avoid potential confounders.