Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain

Dimovasili, Christina; Fair, Ashley E.; Garza, Isabella; Batterman, Katelyn V.; Mortazavi, Farzad; Moore, Tara; Rosene, Douglas L.

doi:10.1007/s11357-022-00621-4

Cited by 27 publications

(25 citation statements)

References 87 publications

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“…Unexpectedly, while the total oligodendrocyte density in the lemur corpus callosum had more than doubled during aging, the majority were stuck in the precursor stage. This result is consistent with a recent study showing (1) a reduced number of new myelinating oligodendrocytes in the corpus callosum of rhesus monkeys during aging and (2) a decreased differentiation potential into mature oligodendrocytes from OPCs that are blocked at the progenitor stage ( Dimovasili et al., 2022 ).…”

Section: Discussionsupporting

confidence: 93%

Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs

Butruille¹,

Sébillot²,

Ávila³

et al. 2023

Stem Cell Reports

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Section: Discussionsupporting

confidence: 93%

Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs

Butruille¹,

Sébillot²,

Ávila³

et al. 2023

Stem Cell Reports

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“…Though this would certainly favor formation of amyloid plaques, the increased Abeta with age could also contribute to myelin/white matter injury as noted below. There is also an age-related decrease in oligodendrocyte precursor cells and formation of new oligodendrocytes which decreases white matter injury repair (Miyamoto et al, 2013;Dimovasili et al, 2022). There is also impairment of OPCs developing into mature oligodendrocytes in aging white matter (Bagi et al, 2018).…”

Section: Multiple Mechanisms Of White Matter (Wm) Injury In Ad Agementioning

confidence: 99%

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

Sharp

DeCarli

Jin

et al. 2023

Front. Aging Neurosci.

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We postulate that myelin injury contributes to cholesterol release from myelin and cholesterol dysmetabolism which contributes to Abeta dysmetabolism, and combined with genetic and AD risk factors, leads to increased Abeta and amyloid plaques. Increased Abeta damages myelin to form a vicious injury cycle. Thus, white matter injury, cholesterol dysmetabolism and Abeta dysmetabolism interact to produce or worsen AD neuropathology. The amyloid cascade is the leading hypothesis for the cause of Alzheimer’s disease (AD). The failure of clinical trials based on this hypothesis has raised other possibilities. Even with a possible new success (Lecanemab), it is not clear whether this is a cause or a result of the disease. With the discovery in 1993 that the apolipoprotein E type 4 allele (APOE4) was the major risk factor for sporadic, late-onset AD (LOAD), there has been increasing interest in cholesterol in AD since APOE is a major cholesterol transporter. Recent studies show that cholesterol metabolism is intricately involved with Abeta (Aβ)/amyloid transport and metabolism, with cholesterol down-regulating the Aβ LRP1 transporter and upregulating the Aβ RAGE receptor, both of which would increase brain Aβ. Moreover, manipulating cholesterol transport and metabolism in rodent AD models can ameliorate pathology and cognitive deficits, or worsen them depending upon the manipulation. Though white matter (WM) injury has been noted in AD brain since Alzheimer’s initial observations, recent studies have shown abnormal white matter in every AD brain. Moreover, there is age-related WM injury in normal individuals that occurs earlier and is worse with the APOE4 genotype. Moreover, WM injury precedes formation of plaques and tangles in human Familial Alzheimer’s disease (FAD) and precedes plaque formation in rodent AD models. Restoring WM in rodent AD models improves cognition without affecting AD pathology. Thus, we postulate that the amyloid cascade, cholesterol dysmetabolism and white matter injury interact to produce and/or worsen AD pathology. We further postulate that the primary initiating event could be related to any of the three, with age a major factor for WM injury, diet and APOE4 and other genes a factor for cholesterol dysmetabolism, and FAD and other genes for Abeta dysmetabolism.

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Section: Introductionmentioning

confidence: 99%

“…A decline in newly formed mature oligodendrocytes has been observed in the aged brain ( Soreq et al, 2017 ; Hill et al, 2018 ; Wang et al, 2020 ; Rivera et al, 2021 ; Dimovasili et al, 2022 ). However, OPC density does not seem to decline with age when compared across the lifespan in mice, non-human primates or humans ( Sim et al, 2002 ; Doucette et al, 2010 ; Yeung et al, 2014 ; Wang et al, 2020 ; Dimovasili et al, 2022 ). Although it is generally accepted that the OPC population remains stable in the aged brain, a more recent study found significantly reduced OPC (NG2 + ) density in the corpus callosum of 18-month-old mice ( Rivera et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although it is generally accepted that the OPC population remains stable in the aged brain, a more recent study found significantly reduced OPC (NG2 + ) density in the corpus callosum of 18-month-old mice ( Rivera et al, 2021 ). Nonetheless, the inability of OPCs to differentiate into mature oligodendrocytes in the aged brain is not currently debated, and it likely contributes to the reduced capacity for remyelination and declining oligodendrocyte population ( Sim et al, 2002 ; Neumann et al, 2019 ; Segel et al, 2019 ; Rivera et al, 2021 ; Zhang X. et al, 2021 ; Dimovasili et al, 2022 ). This reduced ability to differentiate may be a consequence of a markedly different proteome in aged OPCs ( de la Fuente et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain

Murray

Vecchiarelli

Tremblay

2023

Front. Aging Neurosci.

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Consumption of cannabis is on the rise as public opinion trends toward acceptance and its consequent legalization. Specifically, the senior population is one of the demographics increasing their use of cannabis the fastest, but research aimed at understanding cannabis’ impact on the aged brain is still scarce. Aging is characterized by many brain changes that slowly alter cognitive ability. One process that is greatly impacted during aging is axonal myelination. The slow degradation and loss of myelin (i.e., demyelination) in the brain with age has been shown to associate with cognitive decline and, furthermore, is a common characteristic of numerous neurological diseases experienced in aging. It is currently not known what causes this age-dependent degradation, but it is likely due to numerous confounding factors (i.e., heightened inflammation, reduced blood flow, cellular senescence) that impact the many cells responsible for maintaining overall homeostasis and myelin integrity. Importantly, animal studies using non-human primates and rodents have also revealed demyelination with age, providing a reliable model for researchers to try and understand the cellular mechanisms at play. In rodents, cannabis was recently shown to modulate the myelination process. Furthermore, studies looking at the direct modulatory impact cannabis has on microglia, astrocytes and oligodendrocyte lineage cells hint at potential mechanisms to prevent some of the more damaging activities performed by these cells that contribute to demyelination in aging. However, research focusing on how cannabis impacts myelination in the aged brain is lacking. Therefore, this review will explore the evidence thus far accumulated to show how cannabis impacts myelination and will extrapolate what this knowledge may mean for the aged brain.

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Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain

Cited by 27 publications

References 87 publications

Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs

Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain

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