Sex Differences in Mitochondrial Function Following a Controlled Cortical Impact Traumatic Brain Injury in Rodents

Kalimon, Olivia J.; Sullivan, Patrick G.

doi:10.3389/fnmol.2021.753946

Cited by 13 publications

(4 citation statements)

References 37 publications

(84 reference statements)

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“…Microglial sexual dimorphism has been taken under consideration in the context of AD and synaptic function, ischemic stroke, and traumatic brain injury [549][550][551][552]. Of note, microglial responses to environmental challenges occur in a sex-and time-dependent manner.…”

Section: Synapsesmentioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

103

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ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell–cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.

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Section: Synapsesmentioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

103

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“…Common causes of TBI are violent hits to the head or objects penetrating through the skull and into the brain. The pathophysiology of TBI is complex [85], involving neuroinflammation [86,87], oxidative stress [88], mitochondrial dysfunction [89,90], demyelination, and other mechanisms [91]. Excitotoxicity is at the core of neural loss in response to TBI.…”

Section: Naag In Traumatic Brain Injurymentioning

confidence: 99%

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Morland

Nordengen

2022

IJMS

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N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG—for instance by inhibiting GCPII—is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels.

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“… 34 There appears to be sex differences in mitochondrial function in naïve mice; however, there is little information available regarding sex differences in mitochondrial function post-TBI (reviewed by Kalimon and colleagues in 2021). 35 …”

Section: Introductionmentioning

confidence: 99%

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice

Kalimon,

Vekaria,

Velmurugan

et al. 2023

Neurotrauma Reports

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Traumatic brain injury (TBI) is caused by an impact or penetrating injury to the head resulting in abnormal brain function. Mitochondrial dysfunction is an important hallmark of TBI and has been thoroughly studied in male rodent models of brain injury, but relatively little is known about these outcomes in females. These studies were designed to examine sex as a biological variable for mitochondria-related outcomes after the severe controlled cortical impact (CCI) mouse model of TBI. Synaptic and non-synaptic mitochondria were isolated from the sham- or CCI-injured cortex as well as the hippocampus ipsilateral to the craniotomy 3, 12, 24, or 48 h post-surgery, and then bioenergetics were measured. Subtle variations were observed in the timeline of mitochondrial dysfunction between sexes. Non-synaptic cortical mitochondria from injured females showed early impairment at 12 h post-CCI compared to mitochondria from injured males at 24 h post-CCI. Contrastingly, in the synaptic fraction, mitochondria from injured males showed early impairment at 12 h post-CCI, whereas mitochondria from injured females showed impairment at 24 h post-CCI. Based on bioenergetic impairments at 24 h post-CCI, synaptic and non-synaptic mitochondrial calcium loading was also measured at this time point. Consistent with bioenergetic data at 24 h, non-synaptic mitochondria from injured males had increased calcium loading compared to uninjured control, but this effect was not observed in females. Finally, histological assessment of cortical tissue sparing in each sex was measured at 7 days post-injury. There was a lack of sex-based differences in cortical tissue sparing after severe CCI. Overall, there were some subtle sex differences in mitochondrial outcomes after CCI, but these findings were not statistically significant. This study highlights the importance of utilizing both sexes when measuring mitochondrial function after severe CCI.

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Sex Differences in Mitochondrial Function Following a Controlled Cortical Impact Traumatic Brain Injury in Rodents

Cited by 13 publications

References 37 publications

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice

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