Metabolic Profiling of 5xFAD Mice Hippocampal Interstitial Fluid after Cognitive Stimulation: a Pilot Study

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Published: Nov 11, 2025
DOI: https://doi.org/10.18097/BMCRM00291
Keywords:
Alzheimer`s disease; hippocampus; microdialysis; NMR spectroscopy; metabolism; ketone bodies

Main Article Content

Yu.K. Komleva
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia
A.S. Averchuk
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia
D.V. Chistyakov
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1 Leninskie Gory, 119234, Moscow, Russia; The Patrice Lumumba Peoples` Friendship University of Russia, 6 Miklukho-Maklaya str., 117198, Moscow, Russia
V.G. Vasil’ev
The Patrice Lumumba Peoples` Friendship University of Russia, 6 Miklukho-Maklaya str., 117198, Moscow, Russia
V.A. Ivlev
The Patrice Lumumba Peoples` Friendship University of Russia, 6 Miklukho-Maklaya str., 117198, Moscow, Russia
V.I. Zhdankina
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia
M.V. Kukla
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia
A.N. Lukyanchuk
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia; V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznaka str., 660022, Krasnoyarsk, Russia
I.V. Potapenko
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia
A.B. Salmina
Russian Center of Neurology and Neurosciences, 80 Volokolamskoye Highway, 125367, Moscow, Russia

Abstract

Alzheimer`s disease (AD) is increasingly viewed as a condition associated with disruptions in brain energy metabolism, contributing to synaptic and cognitive impairments. While metabolic disturbances in AD are well characterized under resting conditions, much less is known about the hippocampal response to cognitive stimulation that requires high metabolic flexibility. In this pilot study, using in vivo microdialysis and highresolution NMR spectroscopy, we analyzed the metabolic profile of interstitial fluid in the hippocampus of 5xFAD transgenic mice and control C57BL/6 animals on days 7 and 28 following cognitive training in a conditioned passive avoidance paradigm. Among the metabolites examined, significant differences were found for acetone: in 5xFAD animals on day 28, its concentration was markedly lower compared to controls, indicating a limited ability to maintain ketone metabolism in the delayed post-training period. Other metabolites (acetate, lactate, caprate, isobutyrate, and glycine) did not show significant differences between groups; however, the observed changes may indicate shifts in the utilization of alternative energy substrates. These data suggest reduced hippocampal metabolic plasticity in transgenic animals, particularly in the late phase following cognitive stimulation, which could potentially limit long-term cognitive adaptation. Despite the limitations of this pilot study, the results highlight the potential of an approach combining metabolic profiling in vivo for the early detection of metabolic disturbances and the search for potential biomarkers of neurodegenerative processes in AD.

Article Details

How to Cite
Komleva, Y., Averchuk, A., Chistyakov, D., Vasil’ev, V., Ivlev, V., Zhdankina, V., Kukla, M., Lukyanchuk, A., Potapenko, I., & Salmina, A. (2025). Metabolic Profiling of 5xFAD Mice Hippocampal Interstitial Fluid after Cognitive Stimulation: a Pilot Study. Biomedical Chemistry: Research and Methods, 8(4), e00291. https://doi.org/10.18097/BMCRM00291
Issue
Vol. 8 No. 4 (2025): Online first
Section
EXPERIMENTAL RESEARCH

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