The amino acid transporter SLC6A15 is a regulator of hippocampal neurochemistry and behavior

Santarelli, Sara; Namendorf, Christian; Anderzhanova, Elmira; Gerlach, Tamara; Bedenk, Benedikt T.; Kaltwasser, Sebastian F.; Wagner, Klaus V.; Labermaier, Christiana; Reichel, Judith M.; Drgonová, Jana; Czisch, Michael; Uhr, Manfred; Schmidt, Mathias

doi:10.1016/j.jpsychires.2015.07.012

Cited by 18 publications

(11 citation statements)

References 33 publications

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“…In addition, the expression levels of GluR1 in hippocampus, particularly in dentate gyrus, were reported to be significantly affected by levels of slc6a15. The results of the study showed that slc6a15 levels affect HPA axis activation under chronic stress conditions, regulating anxiety and depressive behaviors and affecting GluR1 expression in hippocampus [78].…”

Section: Depressionmentioning

confidence: 91%

“…SLC6A15, a neutral amino acid transporter expressed in neurons, is recommended as a candidate gene for major depression and stress vulnerability with glutamate content, a key neurotransmitter regulating stress response in the hippocampus [78]. A single nucleotide polymorphism in this gene shows all the markers of altered volume, glutamate levels, and hypothalamus-pituitaryadrenal axis activity and major depression [78].…”

Section: Depressionmentioning

confidence: 99%

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The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

Ayka¹,

Şehirli²

2020

Clin Psychopharmacol Neurosci

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The solute carrier (SLC) superfamily is one of the major subgroups of membrane proteins in mammalian cells. The solute carrier proteins include more than 400 different membrane-spanning solute carriers organized with 65 families in the human. In solute carrier family neurons, neurotransmitter is considered to be a pharmacological target of neuropsychiatric drugs because of their important role in the recovery of neurotransmitters such as GABA, glutamate, serotonin, dopamine and noradrenaline and regulation of their concentration in synaptic regions. Therefore, solute carrier transporters play vital and different roles in neurodegenerative disorders. In this article, the role of solute carrier transporters in neurodegenerative disorders such as Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Parkinson's diseases, depression, post-traumatic stress disorder, dementia, schizophrenia, and Epilepsy reviewed and discussed to see how defects or absences in SLC transporter cause neurodegenerative disorders. In this review, we try to summarize what is known about solute carriers with respect to brain distribution and expression. The review summarizes current knowledge on the roles of solute carrier transporters in neurodegenerative disorders.

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Section: Depressionmentioning

confidence: 91%

Section: Depressionmentioning

confidence: 99%

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

Ayka¹,

Şehirli²

2020

Clin Psychopharmacol Neurosci

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“…The presence of a risk allele was associated with down-regulation of Scl6a15 expression in hippocampus, with alterations in hippocampal volume, HPA axis activity and performance on cognitive tasks (Kohli et al, 2011; Schuhmacher et al, 2013). Manipulation of SLC6A15 in mice alters hippocampal glutamate levels, and loss of the gene protected against negative effects of chronic stress, whereas overexpression increased stress vulnerability (Santarelli et al, 2015, 2016). Rare coding variants in SLC6A15 that increase proline uptake have been identified in a sample of major depression (Quast et al, 2013).…”

Section: Convergence Across Animal Models and Human Depressionmentioning

confidence: 99%

Treatment resistant depression: A multi-scale, systems biology approach

Akil

Gordon

Hen

et al. 2018

Neuroscience & Biobehavioral Reviews

363

230

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An estimated 50% of depressed patients are inadequately treated by available interventions. Even with an eventual recovery, many patients require a trial and error approach, as there are no reliable guidelines to match patients to optimal treatments and many patients develop treatment resistance over time. This situation derives from the heterogeneity of depression and the lack of biomarkers for stratification by distinct depression subtypes. There is thus a dire need for novel therapies. To address these known challenges, we propose a multi-scale framework for fundamental research on depression, aimed at identifying the brain circuits that are dysfunctional in several animal models of depression as well the changes in gene expression that are associated with these models. When combined with human genetic and imaging studies, our preclinical studies are starting to identify candidate circuits and molecules that are altered both in models of disease and in patient populations. Targeting these circuits and mechanisms can lead to novel generations of antidepressants tailored to specific patient populations with distinctive types of molecular and circuit dysfunction.

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“…In a SLC6A15 regulatory region, risk allele carriers for a single nucleotide polymorphism (SNP) show altered glutamate levels, hippocampal volume, and hypothalamus-pituitary-adrenal axis activity. These markers are all associated with major depression [210,211].…”

Section: Other Possible Inherited Conditions Related To Amino Acid Trmentioning

confidence: 99%

Amino Acid Transport Defects in Human Inherited Metabolic Disorders

Yahyaoui

Pérez‐Frías

2019

IJMS

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Amino acid transporters play very important roles in nutrient uptake, neurotransmitter recycling, protein synthesis, gene expression, cell redox balance, cell signaling, and regulation of cell volume. With regard to transporters that are closely connected to metabolism, amino acid transporter-associated diseases are linked to metabolic disorders, particularly when they involve different organs, cell types, or cell compartments. To date, 65 different human solute carrier (SLC) families and more than 400 transporter genes have been identified, including 11 that are known to include amino acid transporters. This review intends to summarize and update all the conditions in which a strong association has been found between an amino acid transporter and an inherited metabolic disorder. Many of these inherited disorders have been identified in recent years. In this work, the physiological functions of amino acid transporters will be described by the inherited diseases that arise from transporter impairment. The pathogenesis, clinical phenotype, laboratory findings, diagnosis, genetics, and treatment of these disorders are also briefly described. Appropriate clinical and diagnostic characterization of the underlying molecular defect may give patients the opportunity to avail themselves of appropriate therapeutic options in the future.

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The amino acid transporter SLC6A15 is a regulator of hippocampal neurochemistry and behavior

Cited by 18 publications

References 33 publications

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders

Treatment resistant depression: A multi-scale, systems biology approach

Amino Acid Transport Defects in Human Inherited Metabolic Disorders

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