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Novel mitochondrial mechanisms of cognitive regulation in subjects with cognitive impairments

Published online by Cambridge University Press:  19 July 2023

B. Bigio ,
R. Lima-Filho ,
O. Barnhill ,
F. Sudo ,
C. Drummond ,
N. Assunção ,
B. Vanderborght ,
F. Tovar-Moll ,
P. Mattos  and
S. Ferreira
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B. Bigio*
Affiliation:
Department of Psychiatry, New York University Grossman School of Medicine, New York, United States
R. Lima-Filho
Affiliation:
Institute of Medical Biochemistry Leopoldo de Meis, Rio de Janeiro, Brazil
O. Barnhill
Affiliation:
Rockefeller University, New York, United States
F. Sudo
Affiliation:
Institute of Medical Biochemistry Leopoldo de Meis, Rio de Janeiro, Brazil
C. Drummond
Affiliation:
D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
N. Assunção
Affiliation:
D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
B. Vanderborght
Affiliation:
D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
F. Tovar-Moll
Affiliation:
D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
P. Mattos
Affiliation:
D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
S. Ferreira
Affiliation:
Institute of Medical Biochemistry Leopoldo de Meis, Rio de Janeiro, Brazil
F. De Felice
Affiliation:
Queen’s University, Kingston, Canada
M. Lourenco
Affiliation:
Institute of Medical Biochemistry Leopoldo de Meis, Rio de Janeiro, Brazil
C. Nasca
Affiliation:
Department of Psychiatry, New York University Grossman School of Medicine, New York, United States Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, United States
*
*Corresponding author.

Abstract

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Introduction

Prior mechanistic studies in rodents showed decreased levels of the pivotal mitochondrial metabolite acetyl-L-carnitine (LAC) in relation to cognitive deficits and depressive-like behavior (Neuron 2017, 10.1016/j.neuron.2017.09.020, PNAS 2013, 10.1073/pnas.1216100110), providing the basis for the current translational study.

Objectives

The main objective of this work was to ascertain the role of this specific mitochondrial signaling pathway in subjects with cognitive impairments (CI), and potential sex differences in these mechanisms.

Methods

We used computational approaches, ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) and available plasma samples from a well-characterized cohort of 71 subjects, including subjects with CI and age- and sex-matched cognitively healthy controls (HC).

Results

Our newest findings showed decreased levels of LAC in subjects with CI as compared to age- and sex-matched HC. We also found important sex differences in carnitine levels in relation to cognitive function as assessed by using the Mini Mental Status Exam (MMSE). Specifically, the degree of carnitine deficiency reflected the severity of cognitive dysfunction in a sex-specific manner. Using computational approaches, we found that the integration of these mitochondrial measures with canonical biomarkers improves diagnostic accuracy.

Conclusions

The current findings of sex differences in carnitine deficiency in subjects with CI suggest a possible sex-specific mitochondrial phenotype of vulnerability to cognitive dysfunction, and point to LAC-related mitochondrial metabolism as a new signaling pathway of cognitive regulation.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 66 , Special Issue S1: Abstracts of the 31st European Congress of Psychiatry , March 2023 , pp. S611
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association
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