Abstract
Amino acid neurotransmitters are responsible for many physiological and pathological processes, and their cerebral concentrations respond to external influences such as the light–dark cycle and to the synthesis, release, and recapture rhythms and form part of the biochemical relationships derived from excitatory-inhibitory (E/I), glutamine–glutamate sum (GLX), glutamatergic processing (glutamine–glutamate ratio) and excitotoxic indexes. The changes in these variables during a 24-h period (1 day) are important because they allow organisms to adapt to external stimuli and form part of physiological processes. Under pathological conditions, the damage produced by acute events may depend on diurnal variations. Therefore, it is important to analyze the extracellular levels of amino acids as well as the above-mentioned indexes over a 24-h period. We focused on determining the cerebrospinal fluid levels of different amino acid neurotransmitters, and the E/I, GLX, glutamatergic processing and excitotoxic indexes, determined by microdialysis over a 24-h cycle. Our results showed significant changes during the 24-h light/dark cycle. Specifically, we found increments in the levels of glutamate (325%), GABA (550%), glutamine (300%), glycine (194%), alanine (304%) and the GLX index (263%) throughout the day, and the maximum levels of glutamate, glutamine, glycine, and alanine were obtained during the last period of the light period. In conclusion, the concentration of some amino acid neurotransmitters and the GLX index show variations depending on the light–dark cycle.
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Acknowledgements
We thank Sergio Humberto Larios-Godínez and Biol. Ricardo Trejo-Chávez for the technical assistance provided. We thank the “Programa de Posgrado de Ciencias Biológicas y Programa de Posgrado Ciencias Médicas, Odontológicas y de la Salud, UNAM” and Scholarship No. 547418 (CONACyT, Mexico) for supporting Adan Pérez-Arredondo during his studies at the Doctoral Program of the Medical, Dental and Health Sciences, Clinical Experimental Health Research, Clinical Pharmacology, UNAM, Mexico.
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We appreciate the financial support received from the National Institutes of Health [No. 04/2013, 2014, 2015, Federal Found, Program E022, National Institute of Pediatric], CONACyT No. 152510, and DGAPA-PAPIT No. IN223417 and IN228320. FE-R, LC-A, NC-R, EC-U, RG-G and LN are SNI-CONACyT Fellows. Scholarships from the CONACyT (Mexico) Doctoral Program of Medical, Dental and Health Sciences, Clinical Experimental Health Research, Clinical Epidemiology, UNAM, supported AP-A during his studies [No. 547418].
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Conceptualization: FE-R, LC-A, AP-A and LN. Formal analysis: FE-R, VA-A, AP-A, LC-A and LN. Funding acquisition: LC-A and LN. Investigation: FE-R, VA-A, EC-U, and NC-R. Project administration: LC-A and LN. Supervision: LC-A, RG-G and LN. Writing—original draft: FE-R, RG-G, EC-U, AP-A, LC-A and LN. All the authors have read and agreed to the published version of the manuscript.
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All animal procedures were strictly performed following the National Institutes of Health Guideline for the Care and Use of Laboratory Animals, the local guidelines on the ethical use of animals drafted by Mexico’s Federal Ministry of Health Ministry, and the Mexican Official Standard NOM-062-ZOO-1999 and are part of project 04-2013, which was approved by Research Boards of the National Institute of Pediatrics (NIP), Mexico City, registered at the Office for Human Research Protection of the NIH (http://ohrp.cit.nih.gov/search/search.aspx) with number IRB00008064, and approved by the NIP, Committee of Laboratory Animal Use and Care, and the local Research and Ethics Committee of the Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM) (Protocol 128-2009).
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Estrada-Rojo, F., Carmona-Aparicio, L., Arriaga-Avila, V. et al. Effects of time-of-day on the concentration of defined excitatory and inhibitory amino acids in the cerebrospinal fluid of rats: a microdialysis study. Amino Acids 53, 1597–1607 (2021). https://doi.org/10.1007/s00726-021-03070-z
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DOI: https://doi.org/10.1007/s00726-021-03070-z