Abstract
In this study the subcellular modifications undergone by cerebral cortex mitochondrial metabolism in chronic hypertension during aging were evaluated. The catalytic properties of regulatory energy-linked enzymes of Tricarboxylic Acid Cycle (TCA), Electron Transport Chain (ETC) and glutamate metabolism were assayed on non-synaptic mitochondria (FM, located in post-synaptic compartment) and on intra-synaptic mitochondria of pre-synaptic compartment, furtherly divided in “light” (LM) and “heavy” (HM) mitochondria, purified form cerebral cortex of normotensive Wistar Kyoto Rats (WKY) versus Spontaneously Hypertensive Rats (SHR) at 6, 12 and 18 months. During physiological aging, the metabolic machinery was differently expressed in pre- and post-synaptic compartments: LM and above all HM were more affected by aging, displaying lower ETC activities. In SHR at 6 months, FM and LM showed an uncoupling between TCA and ETC, likely as initial adaptive response to hypertension. During pathological aging, HM were particularly affected at 12 months in SHR, as if the adaptive modifications in FM and LM at 6 months granted a mitochondrial functional balance, while at 18 months all the neuronal mitochondria displayed decreased metabolic fluxes versus WKY. This study describes the effects of chronic hypertension on cerebral mitochondrial energy metabolism during aging through functional proteomics of enzymes at subcellular levels, i.e. in neuronal soma and synapses. In addition, this represents the starting point to envisage an experimental physiopathological model which could be useful also for pharmacological studies, to assess drug actions during the development of age-related pathologies that could coexist and/or are provoked by chronic hypertension.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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This research was funded by Consorzio Italiano Tecnologie Farmaci Invecchiamento – CITFI and by the Catholic Universitary Center (Centro Universitario Cattolico) of the “Conferenza Episcopale Italiana” (CEI), Rome, Italy.
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Conceptualization, RFV.; methodology, RFV. and AG.; validation, RFV., AG; formal analysis, AG and FF; investigation, AG and FF; data curation, RFV; writing—original draft preparation, FF; writing—review and editing, RFV and FF; supervision, RFV; project administration, RFV; funding acquisition, RFV. All authors have read and agreed to the published version of the manuscript.
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Villa, R.F., Ferrari, F. & Gorini, A. Effects of Chronic Hypertension on the Energy Metabolism of Cerebral Cortex Mitochondria in Normotensive and in Spontaneously Hypertensive Rats During Aging. Neuromol Med 26, 2 (2024). https://doi.org/10.1007/s12017-023-08772-z
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DOI: https://doi.org/10.1007/s12017-023-08772-z