scholarly journals Mechanisms of Glutamate Transport

2013 ◽  
Vol 93 (4) ◽  
pp. 1621-1657 ◽  
Author(s):  
Robert J. Vandenberg ◽  
Renae M. Ryan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Structural Basis ◽  
Broad Perspective ◽  
Excitatory Neurotransmitter ◽  
Brain Functions ◽  
Transporter Family ◽  
The Central Nervous System

l-Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and plays important roles in a wide variety of brain functions, but it is also a key player in the pathogenesis of many neurological disorders. The control of glutamate concentrations is critical to the normal functioning of the central nervous system, and in this review we discuss how glutamate transporters regulate glutamate concentrations to maintain dynamic signaling mechanisms between neurons. In 2004, the crystal structure of a prokaryotic homolog of the mammalian glutamate transporter family of proteins was crystallized and its structure determined. This has paved the way for a better understanding of the structural basis for glutamate transporter function. In this review we provide a broad perspective of this field of research, but focus primarily on the more recent studies with a particular emphasis on how our understanding of the structure of glutamate transporters has generated new insights.

scholarly journals Membrane topology of the high-affinity L-glutamate transporter (GLAST-1) of the central nervous system.

1996 ◽  
Vol 135 (6) ◽  
pp. 1867-1877 ◽  
Author(s):  
S Wahle ◽  
W Stoffel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transmembrane Domain ◽  
Glutamate Transporter ◽  
Membrane Topology ◽  
High Affinity ◽  
Transporter Family ◽  
The Central Nervous System

The membrane topology of the high affinity, Na(+)-coupled L-glutamate/L-aspartate transporter (GLAST-1) of the central nervous system has been determined. Truncated GLAST-1 cDNA constructs encoding protein fragments with an increasing number of hydrophobic regions were fused to a cDNA encoding a reporter peptide with two N-glycosylation sites. The respective cRNA chimeras were translated in vitro and in vivo in Xenopus oocytes. Posttranslational N-glycosylation of the two reporter consensus sites monitors the number, size, and orientation of membrane-spanning domains. The results of our experiments suggest a novel 10-transmembrane domain topology of GLAST-1, a representative of the L-glutamate neurotransmitter transporter family, with its NH2 and COOH termini on the cytoplasmic side, six NH2-terminal hydrophobic transmembrane alpha-helices, and four COOH-terminal short hydrophobic domains spanning the bilayer predicted as beta-sheets.

scholarly journals Memantine as an Augmentation Therapy for Anxiety Disorders

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Thomas L. Schwartz ◽  
Umar A. Siddiqui ◽  
Shafi Raza
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nmda Receptor ◽  
Adverse Events ◽  
Nmda Receptor Antagonist ◽  
Augmentation Therapy ◽  
Treatment Resistant ◽  
Excitatory Neurotransmitter ◽  
The Central Nervous System ◽  
Development Of Anxiety

Objective. Glutamate, an excitatory neurotransmitter in the central nervous system (CNS), may play a role in the development of anxiety. Memantine partially blocks N-methyl-D-aspartate (NMDA) receptors' glutamate channels located in the CNS. This paper evaluates memantine as an augmentation therapy for treatment of anxiety.Methods. 15 consecutive partially responding anxious patients were treated with adjunctive memantine for 10 weeks. Memantine was dosed 5–20 mg/day.Result. Memantine augmentation resulted in clinically relevant reduction in anxiety symptoms when compared to baseline. Forty percent of patients achieved remission (HAM-A ≥ 7). Memantine improved sleep quality. Mean dose was 14 mg/d (range 5–20 mg/d). Typical adverse events included nausea and headache.Conclusion. The NMDA receptor antagonist memantine may be an effective augmentation therapy in patients with treatment-resistant anxiety.

scholarly journals Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa

2018 ◽  
Vol 98 (1) ◽  
pp. 477-504 ◽  
Author(s):  
Robert Dantzer
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Long Range ◽  
Immune Cells ◽  
Short Range ◽  
The Body ◽  
Fine Tuning ◽  
Brain Functions ◽  
The Central Nervous System

Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous system has evolved over time, since the first demonstrations of immune influences on brain functions. The necessary complementarity of these two modes of communication will then be discussed. Finally, a few examples will illustrate how dysfunction in these communication pathways results in what was formerly considered in psychiatry and immunology to be strict organ pathologies.

scholarly journals Age-specific changes in cognitive function

2020 ◽  
Vol 22 ◽  
pp. 01015
Author(s):  
Alena Sidenkova ◽  
Anara Sorokina ◽  
Vasilisa Litvinenko ◽  
Artem Novoselov ◽  
Oleg Serdyuk
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Aging ◽  
Statistical Data ◽  
Dynamic Heterogeneity ◽  
Brain Functions ◽  
Pathological Aging ◽  
The Central Nervous System ◽  
Study Participants ◽  
Higher Brain Functions

Currently, the number of cases of pathological aging of the central nervous system, represented by a violation of cognitive functions, is increasing. But there is a social request to prolong the physical and mental activity of older people. The study of the dynamics of cognitive aging is timely and relevant. The article contains a report on a cohore non-repeating study of higher brain functions at various age periods. 148 people involved. Their age is 27 -74 years. They are right handed. We applied the screening neuropsychological method. Statistical data processing was performed using SPSS Statistics 17.0 (Mann-Whitney U-test). The dynamic heterogeneity of the cognitive profile during aging was revealed. The deterioration in the performance of the graphomotor test was the most age-specific. In older study participants, a decrease in the visual gnosis test correlated with a decrease in non-verbal intelligence. The decrease in executive functions correlated with the growth of neurodynamic disorders in elderly study participants. The results obtained are useful for differentiating normative and pathological aging of the central nervous system.

New dimensions of connectomics and network plasticity in the central nervous system

2017 ◽  
Vol 28 (2) ◽  
pp. 113-132 ◽  
Author(s):  
Diego Guidolin ◽  
Manuela Marcoli ◽  
Guido Maura ◽  
Luigi F. Agnati
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Network Architecture ◽  
Cell Phenotype ◽  
Brain Functions ◽  
Brain Connectome ◽  
Communication Processes ◽  
Cell Components ◽  
The Central Nervous System ◽  
The Brain

AbstractCellular network architecture plays a crucial role as the structural substrate for the brain functions. Therefore, it represents the main rationale for the emerging field of connectomics, defined as the comprehensive study of all aspects of central nervous system connectivity. Accordingly, in the present paper the main emphasis will be on the communication processes in the brain, namely wiring transmission (WT), i.e. the mapping of the communication channels made by cell components such as axons and synapses, and volume transmission (VT), i.e. the chemical signal diffusion along the interstitial brain fluid pathways. Considering both processes can further expand the connectomics concept, since both WT-connectomics and VT-connectomics contribute to the structure of the brain connectome. A consensus exists that such a structure follows a hierarchical or nested architecture, and macro-, meso- and microscales have been defined. In this respect, however, several lines of evidence indicate that a nanoscale (nano-connectomics) should also be considered to capture direct protein-protein allosteric interactions such as those occurring, for example, in receptor-receptor interactions at the plasma membrane level. In addition, emerging evidence points to novel mechanisms likely playing a significant role in the modulation of intercellular connectivity, increasing the plasticity of the system and adding complexity to its structure. In particular, the roamer type of VT (i.e. the intercellular transfer of RNA, proteins and receptors by extracellular vesicles) will be discussed since it allowed us to introduce a new concept of ‘transient changes of cell phenotype’, that is the transient acquisition of new signal release capabilities and/or new recognition/decoding apparatuses.

scholarly journals Neuromedin U Receptor 2-Deficient Mice Display Differential Responses in Sensory Perception, Stress, and Feeding

2006 ◽  
Vol 26 (24) ◽  
pp. 9352-9363 ◽  
Author(s):  
Hongkui Zeng ◽  
Alexander Gragerov ◽  
John G. Hohmann ◽  
Maria N. Pavlova ◽  
Brian A. Schimpf ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Phenotypic Characterization ◽  
Dorsal Horn Neurons ◽  
Brain Functions ◽  
The Central Nervous System ◽  
Central Pain Processing ◽  
Excessive Grooming ◽  
Deficient Mice

ABSTRACT Neuromedin U (NMU) is a highly conserved neuropeptide with a variety of physiological functions mediated by two receptors, peripheral NMUR1 and central nervous system NMUR2. Here we report the generation and phenotypic characterization of mice deficient in the central nervous system receptor NMUR2. We show that behavioral effects, such as suppression of food intake, enhanced pain response, and excessive grooming induced by intracerebroventricular NMU administration were abolished in the NMUR2 knockout (KO) mice, establishing a causal role for NMUR2 in mediating NMU's central effects on these behaviors. In contrast to the NMU peptide-deficient mice, NMUR2 KO mice appeared normal with regard to stress, anxiety, body weight regulation, and food consumption. However, the NMUR2 KO mice showed reduced pain sensitivity in both the hot plate and formalin tests. Furthermore, facilitated excitatory synaptic transmission in spinal dorsal horn neurons, a mechanism by which NMU stimulates pain, did not occur in NMUR2 KO mice. These results provide significant insights into a functional dissection of the differential contribution of peripherally or centrally acting NMU system. They suggest that NMUR2 plays a more significant role in central pain processing than other brain functions including stress/anxiety and regulation of feeding.

Glutamate transporters in the central nervous system of a pond snail

2009 ◽  
pp. NA-NA
Author(s):  
Dai Hatakeyama ◽  
Koichi Mita ◽  
Suguru Kobayashi ◽  
Hisayo Sadamoto ◽  
Yutaka Fujito ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glutamate Transporters ◽  
Pond Snail ◽  
The Central Nervous System

Fast Analytical Sensing Technology: Microelectrode-Based Recordings of Tonic and Phasic Neurotransmitter Signalling in the Mammalian Brain

2018 ◽  
pp. 500-510
Author(s):  
Michelle L. Humeiden ◽  
Jorge E. Quintero ◽  
John T. Slevin ◽  
Greg A. Gerhardt
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Applications ◽  
Mammalian Brain ◽  
Excitatory Neurotransmitter ◽  
Ideal Candidate ◽  
Ca1 Region ◽  
Sensing Technology ◽  
The Central Nervous System ◽  
The Brain

Communication in the nervous system is predominately chemical. However, understanding of neurotransmitter signalling in normal and diseased states remains lacking. Electrochemically based biosensors can detect chemical messengers on a near-real timescale, allowing exploration of neurotransmitter systems to bring into focus the functioning elements of this critical means of communication. Glutamate, the predominant excitatory neurotransmitter of the central nervous system, is an ideal candidate for measurement with biosensors. With biosensors, it has been found that spontaneous glutamate signals in the dentate gyrus are enhanced in kindled animals. Meanwhile, in a model of epilepsy, the utility of detecting and the dynamism of glutamate signalling become apparent as tonic glutamate levels and rapid, spontaneous phasic glutamate signals show a correlation with seizure activity in the CA1 region of rodents. The ability of these biosensors to detect neurotransmitters in the brain is promising for clinical applications to monitor and, eventually, treat epilepsy.

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