Morphometric analysis of the human endoneurial extracellular matrix components during aging

Authors

DOI:

https://doi.org/10.2298/ABS201214006K

Keywords:

endoneurium, collagen type IV, collagen type I, laminin, aging

Abstract

Paper description:

  • Aging affects the extracellular matrix (ECM), which is important for normal axonal functioning and supports axonal regeneration.
  • The endoneurial percentages of ECM proteins in human peripheral nerves harvested from 15 cadavers of 3 age groups (25-44; 45-64; 65-86) were examined morphometrically.
  • After the age of 65 there was a significantly higher presence of collagen type IV than in younger groups and a significantly lower expression of collagen type I and laminin.
  • The age-related imbalance of ECM proteins may modify nerve functions in older people by preventing adequate repair and regeneration.

Abstract: The aim of this study was to analyze the expression of extracellular matrix (ECM) proteins in human endoneurium during aging. We harvested 15 cadaveric sural nerves, distributed in 3 age groups (I: 25-44, II: 45-64, III: 65-86 years old). Histological sections were stained immunohistochemically for the presence of collagen type I, type IV and laminin, and the ImageJ processing program was used in morphometrical analysis to determine the percentages of these endoneurial proteins. In two younger groups, the endoneurial matrix of the sural nerve was composed from about equal proportions of these proteins, which may be considered a favorable microenvironment for the regeneration of nerve fibers. Linear regression analysis showed a significant increase in endoneurial collagen type IV with age, while collagen type I and laminin significantly decreased during the aging process. In cases older than 65 years, remodeling of the endoneurial matrix was observed to be significantly higher for the presence of collagen type IV, and lower for the expression of collagen type I and laminin. This age-related imbalance of ECM proteins could represent a disadvantageous microenvironment for nerve fiber regeneration in older adults. Our findings contribute to the development of therapeutic approaches for peripheral nerve regeneration.

Downloads

Download data is not yet available.

References

Bhatia-Dey N, Kanherkar RR, Stair SE, Makarev EO, Csoka AB. Cellular Senescence as the Causal Nexus of Aging. Front Genet. 2016;7:13.

Goto K, Naito K, Nakamura S, Nagura N, Sugiyama Y, Obata H, Kaneko A, Kaneko K. Protective mechanism against age-associated changes in the peripheral nerves. Life Sci. 2020; 253:117744.

Ceballos D, Cuadras J, Verdú E, Navarro X. Morphometric and ultrastructural changes with ageing in mouse peripheral nerve. J Anat. 1999;195(4):563-76.

Dubovy P, Klusáková I, Svíženská I. A quantitative immunohistochemical study of the endoneurium in the rat dorsal and ventral spinal roots. Histochem Cell Biol. 2002;117:473-80.

Lorimier P, Mezin P, Labat Moleur F, Pinel N, Peyrol S, Stoebner P. Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve. J Histochem Cytochem. 1992;40:859-68.

Geuna S, Raimondo S, Ronchi G, Di Scipio F, Tos P, Czaja K, Fornaro M. Chapter 3: Histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol. 2009;87:27-42.

Stierli S, Napoli I, White IJ, Cattin AL, Monteza Cabrejos A, Garcia Calavia N, Malong L, Ribeiro S, Nihouarn J, Williams R, Young KM, Richardsin WD, Lloyd AC. The regulation of the homeostasis and regeneration of peripheral nerve is distinct from the CNS and independent of a stem cell population. Development. 2018;145:dev170316

Gonzalez-Perez F, Udina E, Navarro X. Extracellular Matrix Components in Peripheral Nerve Regeneration. Int Rev Neurobiol. 2013;108:257-75.

Houschyar KS, Momeni A, Pyles MN, Cha JY, Maan ZN, Duscher D, Jew OS, Siemers F, van Schoonhoven J. The Role of Current Techniques and Concepts in Peripheral Nerve Repair. Plast Surg Int. 2016;2016:4175293.

Carvalho CR, Reis RL, Oliveira JM. Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration. Adv Exp Med Biol. 2020;1249:173-201.

Bilbao J, Schmidt RE. Normal Anatomy of the Peripheral (Sural) Nerve. In: Bilbao J, Schmidt RE, editors. Biopsy diagnosis of peripheral neuropathy. 2nd ed. Springer; 2015. p. 21-41.

Pillutla P, Nix E, Elberson BW, Nagy L. Complete Femoral Nerve Transection with Sural Nerve Cable Graft in a 21‑Month‑Old Child. J Neurosci Rural Pract. 2019;10(1):139-41.

Amaya-Montoya M, Pérez-Londoño A, Guatibonza-García V, Vargas-Villanueva A, Mendivil CO. Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review. Adv Ther. 2020;37(4):1407-24.

Kovacic U, Sketelj J, Bajrović FF. Chapter 26: Age-related differences in the reinnervation after peripheral nerve injury. Int Rev Neurobiol. 2009;87:465-82.

Verdú E, Ceballos D, Vilches JJ, Navarro X. Influence of aging on peripheral nerve function and regeneration. J Peripher Nerv Syst. 2000;5(4):191-208.

Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15(12):786-801.

Jeronimo A, Jeronimo CAD, Filho OAR, Sanada LS, Fazan VPS. Microscopic anatomy of the sural nerve in the postnatal developing rat: a longitudinal and lateral symmetry study. J Anat. 2005;206:93-9.

Bahcelioglu M, Elmas C, Kurkcuoglu A, Calguner E, Erdogan D, Kadioglu D, Gözil R. Age-related immunohistochemical and ultrastructural changes in rat oculomotor nerve. Anat Histol Embryol 2008;37(4):279-84.

Goss JR, Stolz DB, Robinson AR, Zhang M, Arbujas N, Robbins PD, Glorioso JC, Niedernhofer LJ. Premature Aging-related Peripheral Neuropathy in a Mouse Model of Progeria. Mech Ageing Dev. 2011;132(8-9):437-42.

Esquisatto MAM, de Aro AA, Fêo HB, Gomes L. Changes in the connective tissue sheath of Wistar rat nerve with aging. Ann Anat. 2014;196:441-8.

Yuan X, Klein D, Kerscher S, West BL, Weis J, Katona I, Martini R. Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice. J Neurosci. 2018;38(19):4610-20.

Biasibetti E, Bisanzio D, Mioletti S, Amedeo S, Iuliano A, Bianco P, Capucchio MT. Spontaneous Age-related Changes of Peripheral Nerves in Cattle: Morphological and Biochemical Studies. Anat Histol Embryol. 2016;45(2):100-8.

Hill R. Extracellular matrix remodelling in human diabetic neuropathy. J Anat 2009; 214(2):219-25.

Hubert T, Grimal S, Carroll P, Fichard-Carroll A. Collagens in the developing and diseased nervous system. Cell Mol Life Sci 2009;66(7):1223-38.

Koopmans G, Hasse B, Sinis N. Chapter 19: The role of collagen in peripheral nerve repair. Int Rev Neurobiol 2009; 87:363-79.

Uspenskaia O, Liebetrau M, Herms J, Danek A, Hamann GF. Aging is associated with increased collagen type IV accumulation in the basal lamina of human cerebral microvessels. BMC Neurosci. 2004;5:37.

Chen L, Miyamura N, Ninomiya Y, Handa JT. Distribution of the collagen IV isoforms in human Bruch's membrane. Br J Ophthalmol. 2003;87(2):212-5.

Ishiyama A, Mowry SE, Lopez IA, Ishiyama G. Immunohistochemical distribution of basement membrane proteins in the human inner ear from older subjects. Hear Res. 2009;254(1-2):1-14.

Anderson S, Brenner BM. Effect of aging on the renal glomerulus. Am J Med. 1986;80:435-44.

Aszódi A, Legate KR, Nakchbandi I, Fässler R. What mouse mutants teach us about extracellular matrix function. Annu Rev Cell Dev Biol. 2006;22:591-621.

Karsdal MA, Nielsen SH, Leeming DJ, Langholm LL, Nielsen MJ, Manon-Jensen T, Siebuhr A, Gudmann NS, Rønnow S, Sand JM, Daniels SJ, Mortensen JH, Schuppan D. The good and the bad collagens of fibrosis – their role in signaling and organ function. Adv Drug Deliv Rev. 2017;121:43-56.

Genovese F, Manresa AA, Leeming DJ, Karsdal MA, Boor P. The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis? Fibrogenesis Tissue Repair. 2014;7(1):4.

Karsdal MA, Genovese F, Madsen EA, Manon-Jensen T, Schuppan D. Collagen and tissue turnover as a function of age: Implications for fibrosis. J Hepatol. 2016;64(1):103-9.

Sprenger CC, Plymate SR, Reed MJ. Aging-related alterations in the extracellular matrix modulate the microenvironment and influence tumor progression. Int J Cancer. 2010;127(12):2739-48.

Keeley DP, Hastie E, Jayadev R, Kelley LC, Chi Q, Payne SG, Jeger JL, Hoffman BD, Sherwood DR. Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding. Dev Cell. 2020;54(1):60-74.e7.

Foldager CB, Toh WS, Gomoll AH, Olsen BR, Spector M. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues. Cartilage. 2014;5(2):123-32.

Candiello J, Cole GJ, Halfter W. Age-dependent changes in the structure, composition and biophysical properties of a human basement membrane. Matrix Biol. 2010;29(5):402-10.

Kovačič U, Žele T, Marš T, Sketelj J, Bajrović FF. Aging impairs collateral sprouting of nociceptive axons in the rat. Neurobiol Aging. 2010;31(2):339-50.

Downloads

Published

2021-03-19

How to Cite

1.
Kundalić BK, Ugrenović SZ, Jovanović ID, Petrović VS, Petrović AS, Stojanović VR, Antović AR, Kundalić JK, Graovac IS. Morphometric analysis of the human endoneurial extracellular matrix components during aging. Arch Biol Sci [Internet]. 2021Mar.19 [cited 2024Dec.22];73(1):103-10. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/6010

Issue

Section

Articles