STEREOLOGICAL EVIDENCE FOR DE/RE-GENERATION OF MYELIN SHEATHS IN AGED BRAIN WHITE MATTER OF FEMALE RATS

Authors

  • Chen Li Department of Geriatrics Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University
  • Lei Zhang Department of Histology and Embryology, Chongqing Medical University
  • Qiaoya Ma Department of Geriatrics Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University
  • Yong Tang Department of Histology and Embryology, Chongqing Medical University
  • Ya He Department of Geriatrics Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University

DOI:

https://doi.org/10.5566/ias.1436

Keywords:

aging, de/re-myelination, myelin sheath, stereology, white matter

Abstract

Studies have provided qualitative evidence of de-myelination and re-myelination in aged brain white matter. However, there have been no quantitative evidences of degeneration and regeneration of myelin sheaths in white matter. The present study was designed to investigate the quantitative changes in myelin sheaths using unbiased stereological techniques and qualitative changes using electron microscopy in aged brain white matter. Results obtained showed that in brain white matter, the total volume of myelin sheaths of old-age female rats was not significantly different from that of young female rats, but the total length of myelinated fibers in old female rats was significantly decreased by 46.1% when compared with that of young female rats. Myelin sheath volume per unit length of myelinated fibers of old female rats was significantly increased by 43.4% compared with that of young female rats. The mean thickness of myelin sheaths in the white matter of the old rats was significantly increased by 33.3%, when compared with that of young female rats. In age-related loss of myelinated fibers, most fibers had diameters less than 1.4 μm, and myelin sheath thicknesses less than 0.14 μm, but the length of myelinated fibers with diameters more than 0.6 μm and myelin sheath thicknesses more than 0.22 μm increased with age. Myelinated fibers with ratios of myelin sheath thicknesses to myelinated fiber external diameter less than 0.21 were significantly lower in elderly rats than in young rats. However, the total length of myelinated fibers with ratios of myelin sheath thicknesses to myelinated fiber external diameter more than 0.23 was higher in aged rats than in young rats. About 6.58% of myelin sheaths showed degenerative alterations, while 0.88% myelin sheaths showed regenerative alterations. This study provides stereological evidence not only for degeneration but also regeneration of myelin sheaths in aged white matter. 

References

Anderson TJ, Schneider A, Barrie JA, Klugmann M, McCulloch MC, Kirkham D, Kyriakides E, Nave KA, Griffiths IR (1998). Late-onset neurodegeneration in mice with increased dosage of the proteolipid protein gene. J Comp Neurol 394: 506-19.

Biffiger K, Bartsch S, Montag D, Aguzzi A, Schachner M, Bartsch U (2000). Severe hypomyelination of the Murine CNS in the Absence of Myelin-Associated Glycoprotein and Fyn Tyrosine Kinase. J. Neurosci 20: 7430-7.

Blakemore WF (1978). Observations on remyelination in the rabbit spinal cord following demyelination induced by lysolecithin. Neuropathol Appl Neurobiol 4: 47-59.

Chang LW (1990). The neurotoxicology and pathology of organomercury, organolead and organotin. J Toxicol Sci Suppl 4: 125-51.

de Groot JC, de Leeuw FE, Oudkerk M, van Gijn J, Hofman A, Jolles J, Breteler MM (2000). Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol 47: 145-51.

Del Bigio MR, Wilson MJ, Enno T (2003). Chronic hydrocephalus in rats and humans: white matter loss and behavior changes. Ann Neurol 53: 337-46.

Franco-Pons N, Torrente M, Colomina MT, Vilella E (2007). Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination. Toxicol Lett 169: 205-13.

Gundersen HJG (1977). Notes on the estimation of the numerical density of arbitrary particles: The edge effect. J Microsc 111: 219-23.

Gundersen HJG, Bendtsen TF, Korbo L, Marcussen N, Mφller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sφrensen FB, Vesterby A, West MJ (1988a). Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. AMPIS 96: 379-94.

Gundersen HJG, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Mφller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sφrensen FB, Vesterby A, West MJ (1988b). The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96: 857-81.

Gundersen HJG, Jensen EB, Kiêu K, Nielsen J (1999). The efficiency of systematic sampling in stereology—reconsidered. J Microsc 193: 199-211.

Guttmann CR, Jolesz FA, Kikinis R, Killiany RJ, Moss MB, Sandor T, Albert MS (1998). White matter changes with normal aging. Neurology 50: 972-8.

Huang J, Auchus AP (2007). Diffusion tensor imaging of normal appearing white matter and its correlation with cognitive functioning in mild cognitive impairment and Alzheimer's disease. Ann N Y Acad Sci 1097: 259-64.

Jernigan TL, Archibald SL, Fennema-Notestine C, Gamst AC, Stout JC, Bonner J, Hesselink JR (2001). Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiol Aging 22: 581-94.

Karim SA, Barrie JA, McCulloch MC, Montague P, Edgar JM, Kirkham D, Anderson TJ, Nave KA, Griffiths IR, McLaughlin M (2007). PLP overexpression perturbs myelin protein composition and myelination in a mouse model of Pelizaeus-Merzbacher disease. Glia 55: 341-51.

Kemper TL (1994). Neuroanatomical and neuropathological changes during aging and dementia. In: Albert ML, Knoefel JE, editors. Clinical neurology of aging. New York: Oxford University Press. p 3-67.

Kramer JH, Mungas D, Reed BR, Wetzel ME, Burnett MM, Miller BL, Weiner MW, Chui HC (2007). Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology 21: 412-8.

Kroustrup JP, Gundersen HJ (1983). Sampling problems in an heterogeneous organ: quantitation of relative and total volume of pancreatic islets by light microscopy. J Microsc 132: 43-55.

Lassmann H, Bartsch U, Montag D, Schachner M (1997). Dying-back oligodendrogliopathy: a late sequel of myelin-associated glycoprotein deficiency. Glia 19: 104-10.

Li C, Yang S, Zhang W, Shi X, Wang W, Nyengaard JR, Tang Y (2008). Unbiased stereological quantification of unmyelinated fibers in the rat brain white matter. Neurosci Lett 437: 38-41.

Li C, Yang S, Chen L, Lu W, Qiu X, Gundersen HJG, Tang Y (2009). Stereological methods for estimating the myelin sheaths of the myelinated fibers in white matter. Anat Rec 292: 1648-55.

Madureira S, Verdelho A, Ferro J, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Hennerici M, O'brien J, Pantoni L, Salvadori E, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Inzitari D (2006). Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data. Neuroepidemiology 27: 101-16.

Moller A, Strange P, Gundersen HJ (1990). Efficient estimation of cell volume and number using the nucleator and the disector. J Microsc 159: 61-71.

Myers SF (1998). Myelin-sheath abnormalities in the vestibular nerves of chronically diabetic rats. Otolaryngol Head Neck Surg 119: 432-8.

Nagy Z, Westerberg H, Klingberg T (2004). Maturation of white matter is associated with the development of cognitive functions during childhood. J Cogn Neurosci 16: 1227-33.

Nyenggard JR, Gundersen HJG (1992). The isector: a simple and direct method for generating isotropic, uniform random sections from small specimens. J Microsc 165: 427-31.

O’Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS (2001). Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57: 632-8.

Purger D, Gibson EM, Monje M (2016). Myelin plasticity in the central nervous system. Neuropharmacology 110: 563-73.

Pakkenberg B, Gundersen HJG (1997). Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 384: 312-20.

Peters A (2002). Structural changes in the normally aging cerebral cortex of primates. Prog Brain Res 136: 455-65.

Peters A, Josephson K, Vincent SL (1991). Effects of aging on the neuroglial cells and pericytes within area 17 of the rhesus monkey cerebral cortex. J Comp Neurol 299: 384-98.

Peters A, Moss MB, Sethares C (2000). Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J Comp Neurol 419: 364-76.

Peters A, Rosene DL, Moss MB, Kemper TL, Abraham CR, Tigges J, Alber MS (1996). Neurobiological bases of age-related cognitive decline in the rhesus monkey. J Neuropathol Exp Neurol 55: 861-74.

Peters A, Sethares C, Killiany RJ (2001). Effects of age on the thickness of myelin sheaths in monkey primary visual cortex. J Comp Neurol 435: 241-8.

Peters A, Sethares C (2002). Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey. J Comp Neurol 442: 277-91.

Peters A, Sethares C (2003). Is there remyelination during aging of the primate central nervous system? J Comp Neurol 460: 238-54.

Sandell JH, Peters A (2003). Disrupted myelin and axon loss in the anterior commissure of the aged rhesus monkey. J Comp Neurol 466: 14-30.

Shenkin SD, Bastin ME, Macgillivray TJ, Deary IJ, Starr JM, Rivers CS, Wardlaw JM (2005). Cognitive correlates of cerebral white matter lesions and water diffusion tensor parameters in community-dwelling older people. Cerebrovasc Dis 20: 310-8.

Skripuletz T, Lindner M, Kotsiari A, Garde N, Fokuhl J, Linsmeier F, Trebst C, Stangel M (2008). Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent. Am J Pathol 172: 1053-61.

Sterio DC (1984). The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134: 127-36.

West MJ, Slomianka L, Gundersen HJ (1991). Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231: 482-97.

Yang S, Li S, Zhang W, Wang WW, Nyengaard JR, Tang Y (2008). Application of stereological methods to study the white matter and myelinated fibers therein of rat brain. Image Anal Stereol 27:125-32.

Yang S, Li C, Lu W, Zhang W, Wang WW, Tang Y (2009). The myelinated fiber changes in the white matter of aged female Long-Evans rats. J Neurosci Res 87 (7): 1582-90.

Ylikoski R, Ylikoski A, Erkinjuntti T, Sulkava R, Raininko R, Tilvis R (1993). White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 50: 818-24.

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Published

2017-06-23

How to Cite

Li, C., Zhang, L., Ma, Q., Tang, Y., & He, Y. (2017). STEREOLOGICAL EVIDENCE FOR DE/RE-GENERATION OF MYELIN SHEATHS IN AGED BRAIN WHITE MATTER OF FEMALE RATS. Image Analysis and Stereology, 36(2), 111–120. https://doi.org/10.5566/ias.1436

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