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Gilles de la Tourette’s syndrome
Published in David Enoch, Basant K. Puri, Hadrian Ball, Uncommon Psychiatric Syndromes, 2020
David Enoch, Basant K. Puri, Hadrian Ball
There is also some evidence of an association with glutamatergic-related neurotransmission genes. The E219D allele, a missense variant, of the glial high affinity glutamate transporter gene EAAT1 (or SLC1A3), located at 5p13.2, has been reported to be 2.4 times higher (though not conventionally statistically significantly higher; p = 0.09) in a Tourette syndrome cohort compared with controls (Adamczyk et al., 2011). Non-significant (after correcting for multiple testing) associations with Tourette syndrome were also reported in the same year in respect of SAPAP3/DLGAP3 (SAP90/PSD95-associated protein 3; a post-synaptic scaffolding protein which is highly expressed in striatal glutamatergic synapses), located at 1p34.3, for the SNP rs11264126 and two haplotypes containing rs11264126 and rs12141243 (Crane et al., 2011).
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
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.
Effect of acute alarm odor exposure and biological sex on generalized avoidance and glutamatergic signaling in the hippocampus of Wistar rats
Published in Stress, 2018
Damek Homiack, Emma O'Cinneide, Sema Hajmurad, Gary P. Dohanich, Laura A. Schrader
We also assessed expression of GLAST, or EAAT1, which also contributes to glutamate reuptake in the hippocampus. We observed no main effect of TMT exposure (F(TMT)(1,52) = 0.05, p = .83), or interaction between TMT and sex (F(TMT*sex)(1,52) = 1.92, p = .17) with respect to GLAST expression. However, we observed a significant main effect of sex (F(sex)(1,52) = 18.24, p < .001, Figure 4(B)) as females, regardless of treatment condition expressed GLAST at higher levels. Taken together, these results suggest that GLAST is expressed at higher levels in the female hippocampus but is unaffected by TMT exposure.
Efflux proteins at the blood–brain barrier: review and bioinformatics analysis
Published in Xenobiotica, 2018
Massoud Saidijam, Fatemeh Karimi Dermani, Sareh Sohrabi, Simon G. Patching
In terms of individual functionalised amino acids, the ABC transporters all had a lower content of cysteine residues (down to 0.5% in P-gp) than the overall average content in human secondary transport proteins (2.1%). Of the SLC transporters, the OATPs had exceptionally high contents of cysteine residues (4.3%, 4.2%, 3.7%, 3.4% and 4.6%), reflecting the conserved cysteine-rich extracellular loop between the ninth and 10th putative transmembrane domains. The distribution of cysteine residues in OATP1A2 is shown in Figure 16. EAAT1 had a noticeably low content of cysteine residues (0.6%). The content of histidine residues in the ABC transporters was relatively non-variable and similar to the overall average value in human secondary transport proteins (1.8%). One exception was MRP5 with a histidine content of 2.6%. The content of histidines in the SLC transporters was much more variable, ranging from 0.4% in EAAT3 to 3.4% in PMAT. The distribution of histidine residues in PMAT is shown in Figure 16. The relatively high content of histidines in PMAT presumably provides favourable interactions for binding of its monoamine and organic cation substrates. The content of proline residues in the proteins showed some variability with the highest contents in OATP2B1, OAT3 and PMAT (6.9%, 6.5% and 5.8%, respectively), which compares with an overall average of 5.1% in human secondary transport proteins. Tryptophan residues were generally present with higher contents in ABC transporters than in SLC transporters with the highest content in MRP6 (2.3%). A large majority of the SLC transporters had tryptophan contents that were lower than the overall average content in human secondary transporters (1.6%). One exception was OAT3 with a tryptophan content of 2.2%. The content of tyrosine residues in the ABC transporters was relatively non-variable and similar to the overall average value in human secondary transport proteins (3.2%). One exception was MRP6 with a tyrosine content of 1.8%. The content of tyrosines in the SLC transporters was more variable, ranging from 1.6% in EAAT2 to 4.9% in OATP1C1. The distribution of tyrosine residues in OATP1C1 is shown in Figure 16.