Myelin dynamics and its role in cognitive dysfunction in Alzheimer’s disease

CHEN Jing-Fei; XIAO Lan

doi:10.16098/j.issn.0529-1356.2024.04.001

PDF(9757 KB)

Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (4) : 379-385. DOI: 10.16098/j.issn.0529-1356.2024.04.001

Review

Myelin dynamics and its role in cognitive dysfunction in Alzheimer’s disease

Chen Jing-fei ^1*XIAO Lan^2*

Author information +

History +

Abstract

Oligodendrocytes are myelin-forming cells of the central nervous system (CNS). The processes extending from each oligodendrocyte are capable of wrapping axon to form multiple myelin sheaths to ensure efficient and rapid conduction of action potentials along the axon. Recent studies have shown that myelin changes are quite active although most of the myelin sheaths in the adult brain are in a stable state. On the one hand, oligodendrocyte precursor cells continue to differentiate to form new myelin sheaths; on the other hand, a small portion of the formed myelin sheaths degenerate over time. Dynamic changes in myelin sheaths are thought to be a form of neural plasticity in the adult brain, which aims to regulate the function of neural circuits for adapting of new environments or acquiring new skills. In the brains with Alzheimer's disease (AD), myelin degeneration can lead to a compensatory increase in myelin regeneration, but it is still insufficient to compensate for the loss of myelin, and the promotion of new myelin formation is expected to be a new strategy to improve AD-related cognitive dysfunction.

Key words

Oligodendrocyte / Myelin dynamics / Cognitive function

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

CHEN Jing-fei XIAO Lan. Myelin dynamics and its role in cognitive dysfunction in Alzheimer’s disease[J]. Acta Anatomica Sinica. 2024, 55(4): 379-385 https://doi.org/10.16098/j.issn.0529-1356.2024.04.001

References

［1］Baumann N, Pham-Dinh D. Biology of oligodendrocyte and myelin in the mammalian central nervous system ［J］. Physiol Rev, 2001, 81(2): 871-927.

［2］Nave KA. Myelination and the trophic support of long axons ［J］. Nat Rev Neurosci, 2010, 11(4): 275-283.

［3］Stadelmann C, Timmler S, Barrantes-Freer A, et al. Myelin in the central nervous system: structure, function, and pathology ［J］. Physiol Rev, 2019, 99(3): 1381-1431.

［4］Lee Y, Morrison BM, Li Y, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration ［J］. Nature, 2012, 487(7408): 443-448.

［5］Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain ［J］. Nat Neurosci, 2018, 21(5): 683-695.

［6］Wang F, Ren SY, Chen JF, et al. Myelin degeneration and diminished myelin renewal contribute to age-related deficits in memory ［J］. Nat Neurosci, 2020, 23(4): 481-486.

［7］Young KM, Psachoulia K, Tripathi RB, et al. Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling ［J］. Neuron, 2013, 77(5): 873-885.

［8］Bergles DE, Roberts JD, Somogyi P, et al. Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus ［J］. Nature, 2000, 405(6783): 187-191.

［9］Lin SC, Bergles DE. Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus ［J］. Nat Neurosci, 2004, 7(1): 24-32.

［10］Monje M. Myelin plasticity and nervous system function ［J］. Annu Rev Neurosci, 2018, 41: 61-76.

［11］Xin W, Chan JR. Myelin plasticity: sculpting circuits in learning and memory ［J］. Nat Rev Neurosci, 2020, 21(12): 682-694.

[12] Hughes EG, Orthmann-Murphy JL, Langseth AJ, et al. Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex ［J］. Nat Neurosci, 2018, 21(5): 696-706.

［13］Chang KJ, Redmond SA, Chan JR. Remodeling myelination: implications for mechanisms of neural plasticity ［J］. Nat Neurosci, 2016, 19(2): 190-197.

［14］Mckenzie IA, Ohayon D, Li H, et al. Motor skill learning requires active central myelination ［J］. Science, 2014, 346(6207): 318-322.

［15］Steadman PE, Xia F, Ahmed M, et al. Disruption of oligodendrogenesis impairs memory consolidation in adult mice ［J］. Neuron, 2020, 105(1): 150-164.e6.

［16］Pan S, Mayoral SR, Choi HS, et al. Preservation of a remote fear memory requires new myelin formation ［J］. Nat Neurosci, 2020, 23(4): 487-499.

［17］Gibson EM, Purger D, Mount CW, et al. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain ［J］. Science, 2014, 344(6183): 1252304.

［18］Auderset L, Pitman KA, Cullen CL, et al. Low-density lipoprotein receptor-related protein 1 (LRP1) is a negative regulator of oligodendrocyte progenitor cell differentiation in the adult mouse brain ［J］. Front Cell Dev Biol, 2020, 8: 564351.

［19］Keiner S, Niv F, Neumann S, et al. Effect of skilled reaching training and enriched environment on generation of oligodendrocytes in the adult sensorimotor cortex and corpus callosum ［J］. BMC Neurosci, 2017, 18(1): 31.

［20］Tripathi RB, Jackiewicz M, Mckenzie IA, et al. Remarkable stability of myelinating oligodendrocytes in mice ［J］. Cell Rep, 2017, 21(2): 316-323.

［21］Bacmeister CM, Barr HJ, Mcclain CR, et al. Motor learning promotes remyelination via new and surviving oligodendrocytes ［J］. Nat Neurosci, 2020, 23(7): 819-831.

［22］Benamer N, Vidal M, Balia M, et al. Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits ［J］. Nat Commun, 2020, 11(1): 5151.

［23］Yang SM, Michel K, Jokhi V, et al. Neuron class-specific responses govern adaptive myelin remodeling in the neocortex ［J］. Science, 2020, 370(6523):eabd2109.

［24］Arancibia-Cárcamo IL, Ford MC, Cossell L, et al. Node of ranvier length as a potential regulator of myelinated axon conduction speed ［J］. Elife, 2017, 6:e23329.

［25］Etxeberria A, Hokanson KC, Dao DQ, et al. Dynamic modulation of myelination in response to visual stimuli alters optic nerve conduction velocity ［J］. J Neurosci, 2016, 36(26): 6937-6948.

［26］Neely SA, Williamson JM, Klingseisen A, et al. New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination ［J］. Nat Neurosci, 2022, 25(4): 415-420.

［27］Mangin JM, Li P, Scafidi J, et al. Experience-dependent regulation of NG2 progenitors in the developing barrel cortex ［J］. Nat Neurosci, 2012, 15(9): 1192-1194.

［28］Chong SY, Rosenberg SS, Fancy SP, et al. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination ［J］. Proc Natl Acad Sci U S A, 2012, 109(4): 1299-1304.

［29］Barrera K, Chu P, Abramowitz J, et al. Organization of myelin in the mouse somatosensory barrel cortex and the effects of sensory deprivation ［J］. Dev Neurobiol, 2013, 73(4): 297-314.

［30］Hill RA, Patel KD, Goncalves CM, et al. Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division ［J］. Nat Neurosci, 2014, 17(11): 1518-1527.

［31］Murphy KM, Mancini SJ, Clayworth KV, et al. Experience-dependent changes in myelin basic protein expression in adult visual and somatosensory cortex ［J］. Front Cell Neurosci, 2020, 14: 56.

［32］Liu J, Dietz K, Deloyht JM, et al. Impaired adult myelination in the prefrontal cortex of socially isolated mice ［J］. Nat Neurosci, 2012, 15(12): 1621-1623.

［33］Swire M, Kotelevtsev Y, Webb DJ, et al. Endothelin signalling mediates experience-dependent myelination in the CNS ［J］. Elife, 2019, 8: e49493.

［34］Xiao L, Ohayon D, Mckenzie IA, et al. Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning ［J］. Nat Neurosci, 2016, 19(9): 1210-1217.

［35］Kitamura T, Ogawa SK, Roy DS, et al. Engrams and circuits crucial for systems consolidation of a memory ［J］. Science, 2017, 356(6333): 73-78.

［36］Teixeira CM, Pomedli SR, Maei HR, et al. Involvement of the anterior cingulate cortex in the expression of remote spatial memory ［J］. J Neurosci, 2006, 26(29): 7555-7564.

［37］Sakry D, Neitz A, Singh J, et al. Oligodendrocyte precursor cells modulate the neuronal network by activity-dependent ectodomain cleavage of glial NG2 ［J］. PLoS Biol, 2014, 12(11): e1001993.

［38］Chen JF, Liu K, Hu B, et al. Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer’s disease ［J］. Neuron, 2021, 109(14): 2292-2307e5.

［39］Osipovitch M, Asenjo Martinez A, Mariani JN, et al. Human ESC-derived chimeric mouse models of huntington’s disease reveal cell-intrinsic defects in glial progenitor cell differentiation ［J］. Cell Stem Cell, 2019, 24(1): 107-122.e7.

［40］Bartzokis G, Cummings JL, Sultzer D, et al. White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study ［J］. Arch Neurol, 2003, 60(3): 393-398.

［41］Behrendt G, Baer K, Buffo A, et al. Dynamic changes in myelin aberrations and oligodendrocyte generation in chronic amyloidosis in mice and men ［J］. Glia, 2013, 61(2): 273-286.

［42］Mitew S, Kirkcaldie MT, Halliday GM, et al. Focal demyelination in Alzheimer’s disease and transgenic mouse models ［J］. Acta Neuropathol, 2010, 119(5): 567-577.