Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration

Journal of Neurotrauma
Randhall B CarteriLuis Valmor Portela

Abstract

Traumatic brain injury (TBI) increases Ca2+ influx into neurons and desynchronizes mitochondrial function leading to energy depletion and apoptosis. This process may be influenced by brain testosterone (TS) levels, which are known to decrease after TBI. We hypothesized that a TS-based therapy could preserve mitochondrial neuroenergetics after TBI, thereby reducing neurodegeneration. C57BL/6J mice were submitted to sham treatment or severe parasagittal controlled cortical impact (CCI) and were subcutaneously injected with either vehicle (VEH-SHAM and VEH-CCI) or testosterone cypionate (15 mg/kg, TS-CCI) for 10 days. Cortical tissue homogenates ipsilateral to injury were used for neurochemical analysis. The VEH-CCI group displayed an increased Ca2+-induced mitochondrial swelling after the addition of metabolic substrates (pyruvate, malate, glutamate, succinate, and adenosine diphosphate [PMGSA]). The addition of Na+ stimulated mitochondrial Ca2+ extrusion through Na+/Ca2+/Li+ exchanger (NCLX) in VEH-SHAM and TS-CCI, but not in the VEH-CCI group. Reduction in Ca2+ efflux post-injury was associated with impaired mitochondrial membrane potential formation/dissipation, and decreased mitochondrial adenosine triphosphate (ATP)-synthase...Continue Reading

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Citations

Jul 16, 2020·PLoS Computational Biology·Shixin XuHuaxiong Huang
Feb 8, 2021·Behavioural Brain Research·Randhall B CarteriLuis Valmor Portela
Oct 27, 2021·Physiological Reviews·Joanne F Garbincius, John W Elrod

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Datasets Mentioned

BETA
GSE58485

Methods Mentioned

BETA
androgen replacement therapy
Protein Assay
electrophoresis

Software Mentioned

STRINGdb
GraphPad Prism
STRING
Image J
RedeR
Search Tool for the
limma
GEOquery package
DatLab

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