AMP-Activated Protein Kinase Treatment Ameliorates Chronic Restraint Stress Induced Memory Impairment in Early Adolescent Rat by Restoring Metabolite Profile and Synaptic Proteins.

Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 7613461 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-6903 (Electronic) Linking ISSN: 03643190 NLM ISO Abbreviation: Neurochem Res Subsets: MEDLINE

Publication: 1999- : New York, NY : Kluwer Academic/Plenum Publishers
Original Publication: New York, Plenum Press

Stress, Psychological*/metabolism ; Stress, Psychological*/drug therapy ; Memory Disorders*/metabolism ; Memory Disorders*/drug therapy ; AMP-Activated Protein Kinases*/metabolism ; Aminoimidazole Carboxamide*/analogs & derivatives ; Aminoimidazole Carboxamide*/pharmacology ; Aminoimidazole Carboxamide*/metabolism ; Aminoimidazole Carboxamide*/therapeutic use; Animals ; Male ; Rats ; Brain-Derived Neurotrophic Factor/metabolism ; Restraint, Physical ; Ribonucleotides/pharmacology ; Rats, Sprague-Dawley ; Disks Large Homolog 4 Protein/metabolism ; Synapses/metabolism ; Synapses/drug effects

Recent studies highlight the role of brain metabolites in regulation of neuronal signals and behaviour. To understand the underlying mechanism, brain metabolites and associated signaling molecules were examined in early adolescent rat experienced CRS. Rats were tested for their learning and memory ability, and their metabolite profile was evaluated using Gas chromatography-mass spectrometry (GC-MS). Differences in metabolites were examined by variable importance in projection (VIP) and multivariate analysis. Ingenuity Pathway Analysis (IPA) and KEGG ID were performed for the identified metabolites. We found that CRS altered the metabolites that were involved in biosynthesis of steroid hormone, aminoacyl t-RNA, L-Dopa biosynthesis, and metabolism of tyrosine, fatty acid, and purine. Further analysis showed reduction of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR, a metabolite involved in purine metabolism) an AMP kinase activator, influenced the hypoxanthine-guanine phosphoribosyltransferase (HPRT), serotonin transporter (SERT), postsynaptic density protein (PSD) -95, its phosphorylation and brain-derived neurotrophic factor (BDNF) in CRS animals, which displayed deficit in memory. The AICAR treated CRS rats showed improved memory and altered metabolites and other molecules (HPRT, SERT, PSD-95 and BDNF) levels were restored. Our analysis revealed that CRS induced changes in metabolites possibly altered synaptic plasticity and memory in which HPRT, SERT-PSD95-BDNF associated pathway involved. Taken together, our observation provides initial insight into how stress differently influences the metabolic pathway, and associated behaviour. Further study will help to develop pharmacological intervention strategies.
Competing Interests: Declarations Ethical Approval The experimental protocol reviewed and approved by Institutional Animal Ethics Committee (Ref. No.: BDU/IAEC/P28/2024), assuring that the number of animals used was minimum. Competing Interests The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: AICAR; Chronic restraint stress; Gas chromatography; Learning and memory; Mass spectrometry; Metabolite; Serotonergic system

EC 2.7.11.31 (AMP-Activated Protein Kinases)
360-97-4 (Aminoimidazole Carboxamide)
F0X88YW0YK (AICA ribonucleotide)
0 (Brain-Derived Neurotrophic Factor)
0 (Ribonucleotides)
0 (Bdnf protein, rat)
0 (Disks Large Homolog 4 Protein)

Date Created: 20241118 Date Completed: 20241118 Latest Revision: 20241118

20241118

10.1007/s11064-024-04285-8

39556261