NADH-linked mitochondrial respiration in the developing mouse brain is sex-, age- and tissue-dependent.
Respir Physiol Neurobiol
; 266: 156-162, 2019 08.
Article
in En
| MEDLINE
| ID: mdl-31128272
ABSTRACT
Mitochondria play a major role in the brain. Apart from energy production, mitochondria regulate key factors in the activation of cell signaling pathways such as survival, proliferation, and differentiation. While all these processes occur during the physiological development of the brain, it is surprising that the mitochondrial functions and functioning in the brain during the postnatal development remain poorly explored. In this work, we collected samples of brainstem and cortex of mice at postnatal ages 3 (P3), 21 (P21), and at adulthood (3 months old) and evaluated the mitochondrial oxygen consumption after complex I activation. To do so, we used our oxygraph-2â¯K system (OROBOROS) that measures the mitochondrial bioenergetics in saponin-permeabilized tissue punches of 2⯠mg weight. Furthermore, as sex dimorphism in the brain occurs since very early stages of development, we performed experiments in brain samples of male and female mice. Accordingly, the mitochondrial oxygen consumption rate (OCR) was evaluated under activation of complex I (NADH-linked respiration - mitochondrial state 3), and during the inhibition of the complex V (ATP synthase) with oligomycin (mitochondrial state 4). In following, the respiratory control ratio (RCR - state 3/state4) was calculated as an index of mitochondrial oxidative-phosphorylation coupling. Our results show that the activity of the mitochondrial complex I in the brain increases along with the postnatal development in a sex- and tissue-dependent manner, with males showing higher activity than females, and with brainstem tissue showing higher activity than cortex. Our data may contribute to a better understanding of the sex-dependent maturation of the cortex and the cardiorespiratory network located in the brainstem.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiration
/
Brain
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Sex Characteristics
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Mitochondria
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NAD
Limits:
Animals
Language:
En
Journal:
Respir Physiol Neurobiol
Year:
2019
Document type:
Article
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
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NL
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PAISES BAJOS
/
THE NETHERLANDS