Schraut, Karla‐Gerlinde ; Kalnytska, Oleksandra ; Lamp, Daniel ; Jastroch, Martin ; Eder, Matthias ; Hausch, Felix ; Gassen, Nils C. ; Moore, Sarah ; Nagaraj, Nagarjuna ; Lopez, Juan P. ; Chen, Alon ; Schmidt, Mathias V. (2024)
Loss of the psychiatric risk factor SLC6A15 is associated with increased metabolic functions in primary hippocampal neurons.
In: European Journal of Neuroscience, 2020, 53 (2)
doi: 10.26083/tuprints-00016168
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
Major depressive disorder (MDD) is one of the most severe global health problems with millions of people affected, however, the mechanisms underlying this disorder is still poorly understood. Genome‐wide association studies have highlighted a link between the neutral amino acid transporter SLC6A15 and MDD. Additionally, a number of preclinical studies support the function of this transporter in modulating levels of brain neurotransmitters, stress system regulation and behavioural phenotypes related to MDD. However, the molecular and functional mechanisms involved in this interaction are still unresolved. Therefore, to investigate the effects of the SLC6A15 transporter, we used hippocampal tissue from Slc6a15‐KO and wild‐type mice, together with several in‐vitro assays in primary hippocampal neurons. Utilizing a proteomics approach we identified differentially regulated proteins that formed a regulatory network and pathway analysis indicated significantly affected cellular domains, including metabolic, mitochondrial and structural functions. Furthermore, we observed reduced release probability at glutamatergic synapses, increased mitochondrial function, higher GSH/GSSG redox ratio and an improved neurite outgrowth in primary neurons lacking SLC6A15. In summary, we hypothesize that by controlling the intracellular concentrations of neutral amino acids, SLC6A15 affects mitochondrial activity, which could lead to alterations in neuronal structure and activity. These data provide further indication that a pharmacological or genetic reduction of SLC6A15 activity may indeed be a promising approach for antidepressant therapy.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Schraut, Karla‐Gerlinde ; Kalnytska, Oleksandra ; Lamp, Daniel ; Jastroch, Martin ; Eder, Matthias ; Hausch, Felix ; Gassen, Nils C. ; Moore, Sarah ; Nagaraj, Nagarjuna ; Lopez, Juan P. ; Chen, Alon ; Schmidt, Mathias V. |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Loss of the psychiatric risk factor SLC6A15 is associated with increased metabolic functions in primary hippocampal neurons |
| Sprache: | Englisch |
| Publikationsjahr: | 26 Januar 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2020 |
| Ort der Erstveröffentlichung: | Oxford |
| Verlag: | John Wiley & Sons |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | European Journal of Neuroscience |
| Jahrgang/Volume einer Zeitschrift: | 53 |
| (Heft-)Nummer: | 2 |
| DOI: | 10.26083/tuprints-00016168 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/16168 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Major depressive disorder (MDD) is one of the most severe global health problems with millions of people affected, however, the mechanisms underlying this disorder is still poorly understood. Genome‐wide association studies have highlighted a link between the neutral amino acid transporter SLC6A15 and MDD. Additionally, a number of preclinical studies support the function of this transporter in modulating levels of brain neurotransmitters, stress system regulation and behavioural phenotypes related to MDD. However, the molecular and functional mechanisms involved in this interaction are still unresolved. Therefore, to investigate the effects of the SLC6A15 transporter, we used hippocampal tissue from Slc6a15‐KO and wild‐type mice, together with several in‐vitro assays in primary hippocampal neurons. Utilizing a proteomics approach we identified differentially regulated proteins that formed a regulatory network and pathway analysis indicated significantly affected cellular domains, including metabolic, mitochondrial and structural functions. Furthermore, we observed reduced release probability at glutamatergic synapses, increased mitochondrial function, higher GSH/GSSG redox ratio and an improved neurite outgrowth in primary neurons lacking SLC6A15. In summary, we hypothesize that by controlling the intracellular concentrations of neutral amino acids, SLC6A15 affects mitochondrial activity, which could lead to alterations in neuronal structure and activity. These data provide further indication that a pharmacological or genetic reduction of SLC6A15 activity may indeed be a promising approach for antidepressant therapy. |
| Freie Schlagworte: | amino acid transport, cell metabolism, depression, proline, SLC6A15 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-161681 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 26 Jan 2024 13:51 |
| Letzte Änderung: | 01 Feb 2024 07:50 |
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| Suche nach Titel in: | TUfind oder in Google |
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