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Hapln4 is a link protein which stabilizes the binding between lecticans and hyaluronan in perineuronal nets (PNNs) in specific brain regions, including the medial nucleus of the trapezoid body (MNTB). The aim of this study was: (1) to reveal possible age-related alterations in the extracellular matrix composition in the MNTB and inferior colliculus, which was devoid of Hapln4 and served as a negative control, (2) to determine the impact of the Hapln4 deletion on the values of the ECS diffusion parameters in young and aged animals and (3) to verify that PNNs moderate age-related changes in the ECS diffusion, and that Hapln4-brevican complex is indispensable for the correct protective function of the PNNs. To achieve this, we evaluated the ECS diffusion parameters using the real-time iontophoretic method in the selected region in young adult (3 to 6-months-old) and aged (12 to 18-months-old) wild type and Hapln4 knock-out (KO) mice. The results were correlated with an immunohistochemical analysis of the ECM composition and astrocyte morphology. We report that the ECM composition is altered in the aged MNTB and aging is a critical point, revealing the effect of Hapln4 deficiency on the ECS diffusion. All of our findings support the hypothesis that the ECM changes in the MNTB of aged KO animals affect the ECS parameters indirectly, via morphological changes of astrocytes, which are in direct contact with synapses and can be influenced by the ongoing synaptic transmission altered by shifts in the ECM composition.

Titel:	The Effect of Hapln4 Link Protein Deficiency on Extracellular Space Diffusion Parameters and Perineuronal Nets in the Auditory System During Aging.
Autor/in / Beteiligte Person:	Sucha, P ; Chmelova, M ; Kamenicka, M ; Bochin, M ; Oohashi, T ; Vargova, L
Link:	Full Text Finder (Volltext)
Zeitschrift:	Neurochemical research, Jg. 45 (2020), Heft 1, S. 68-82
Veröffentlichung:	1999- : New York, NY : Kluwer Academic/Plenum Publishers ; <i>Original Publication</i>: New York, Plenum Press, 2020
Medientyp:	academicJournal
ISSN:	1573-6903 (electronic)
DOI:	10.1007/s11064-019-02894-2
Schlagwort:	Aging pathology Animals Auditory Pathways pathology Extracellular Matrix metabolism Extracellular Matrix pathology Female Male Mice Mice, Inbred C57BL Mice, Knockout Organ Culture Techniques Peripheral Nerves metabolism Peripheral Nerves pathology Protein Deficiency metabolism Protein Deficiency pathology Trapezoid Body pathology Aging metabolism Auditory Pathways metabolism Diffusion Extracellular Matrix Proteins deficiency Extracellular Space metabolism Nerve Tissue Proteins deficiency Trapezoid Body metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Neurochem Res] 2020 Jan; Vol. 45 (1), pp. 68-82. <i>Date of Electronic Publication: </i>2019 Oct 29. MeSH Terms: Diffusion* ; Aging / metabolism ; Auditory Pathways / metabolism ; Extracellular Matrix Proteins / deficiency ; Extracellular Space / metabolism ; Nerve Tissue Proteins / deficiency ; Trapezoid Body / metabolism ; Aging / pathology ; Animals ; Auditory Pathways / pathology ; Extracellular Matrix / metabolism ; Extracellular Matrix / pathology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Organ Culture Techniques ; Peripheral Nerves / metabolism ; Peripheral Nerves / pathology ; Protein Deficiency / metabolism ; Protein Deficiency / pathology ; Trapezoid Body / pathology References: Trends Neurosci. 2010 Jun;33(6):259-66. (PMID: 20371122) ; J Physiol. 1974 Apr;238(1):1-15. (PMID: 4838796) ; IBRO Rep. 2016 Dec;1:54-60. (PMID: 28713865) ; J Neurosci Res. 2018 Feb;96(2):313-327. (PMID: 28815777) ; Brain. 2010 Aug;133(Pt 8):2331-47. (PMID: 20566484) ; J Neurosci. 2006 Apr 19;26(16):4406-14. (PMID: 16624960) ; Aging (Albany NY). 2017 Jun 28;9(6):1607-1622. (PMID: 28657900) ; Cell Mol Life Sci. 2004 Aug;61(16):2031-45. (PMID: 15316653) ; J Gen Physiol. 2010 Jun;135(6):583-94. (PMID: 20479112) ; Philos Trans R Soc Lond B Biol Sci. 2014 Oct 19;369(1654):20140046. (PMID: 25225104) ; Eur J Neurosci. 2008 Mar;27(6):1373-90. (PMID: 18364019) ; Neuroscience. 1999;92(3):791-805. (PMID: 10426522) ; PLoS One. 2011 Jan 31;6(1):e16666. (PMID: 21304956) ; Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10116-21. (PMID: 9294172) ; PLoS One. 2013 Jul 05;8(7):e68044. (PMID: 23861848) ; J Neurochem. 2018 Dec;147(6):748-763. (PMID: 30125937) ; Hum Brain Mapp. 2005 Aug;25(4):391-401. (PMID: 15852381) ; J Biol Chem. 2003 Oct 17;278(42):41205-12. (PMID: 12888576) ; Neuropathol Appl Neurobiol. 2004 Aug;30(4):338-50. (PMID: 15305979) ; J Neurosci Methods. 1993 Jul;48(3):199-213. (PMID: 8412303) ; J Biol Chem. 2003 Jun 6;278(23):21083-91. (PMID: 12663660) ; Exp Gerontol. 1998 Nov-Dec;33(7-8):837-51. (PMID: 9951627) ; Pflugers Arch. 2004 May;448(2):248-58. (PMID: 14985983) ; Front Neural Circuits. 2014 Jul 29;8:83. (PMID: 25120436) ; J Physiol. 1981 Dec;321:225-57. (PMID: 7338810) ; J Physiol. 2015 Oct 1;593(19):4341-60. (PMID: 26223835) ; Eur J Neurosci. 2005 Oct;22(8):1873-80. (PMID: 16262627) ; J Neurocytol. 1983 Aug;12(4):697-712. (PMID: 6619907) ; Hear Res. 2015 Nov;329:21-32. (PMID: 25580005) ; Eur J Neurosci. 2012 Jul;36(1):2017-24. (PMID: 22536791) ; PLoS One. 2014 Nov 26;9(11):e113444. (PMID: 25426721) ; Physiol Res. 2017 Nov 24;66(5):867-880. (PMID: 29020454) ; Glia. 1999 Oct;28(1):40-8. (PMID: 10498821) ; Neuroscience. 2016 May 26;323:170-82. (PMID: 25595973) ; Front Neuroanat. 2014 Jan 08;7:53. (PMID: 24409124) ; J Comp Neurol. 2006 Feb 1;494(4):559-77. (PMID: 16374793) ; Physiol Rev. 2008 Oct;88(4):1277-340. (PMID: 18923183) ; Acta Neuropathol. 2013 Feb;125(2):215-29. (PMID: 22961619) ; Mol Cell Neurosci. 2003 Sep;24(1):148-59. (PMID: 14550776) ; J Neurophysiol. 1993 Nov;70(5):2035-44. (PMID: 7507522) ; J Comp Neurol. 2012 Jun 1;520(8):1721-36. (PMID: 22121037) ; Pharmacol Ther. 2013 Sep;139(3):313-26. (PMID: 23644076) ; Adv Exp Med Biol. 2015;821:11-7. (PMID: 25416106) ; J Biol Chem. 2006 Jun 30;281(26):17789-800. (PMID: 16644727) ; Cell Tissue Res. 2006 Nov;326(2):311-37. (PMID: 16896951) ; Nat Rev Neurosci. 2019 Aug;20(8):451-465. (PMID: 31263252) ; Exp Neurol. 2015 Dec;274(Pt B):134-44. (PMID: 26387938) ; eNeuro. 2018 Nov 14;5(5):. (PMID: 30456294) ; Hear Res. 2018 Sep;367:32-47. (PMID: 30025262) ; Mol Neurobiol. 2016 Jan;53(1):73-82. (PMID: 25404091) ; J Neurochem. 2010 Sep 1;114(5):1447-59. (PMID: 20584105) ; J Neurosci. 2010 Feb 24;30(8):3113-23. (PMID: 20181608) ; Hippocampus. 2002;12(2):269-79. (PMID: 12000123) Grant Information: 16-10214S Grantová Agentura České Republiky; 19H04754 Grant-in-Aid for Scientific Research on Innovative Areas Contributed Indexing: Keywords: Aging; Diffusion; Extracellular matrix; Extracellular space; Hapln4 Substance Nomenclature: 0 (Extracellular Matrix Proteins) ; 0 (Hapln4 protein, mouse) ; 0 (Nerve Tissue Proteins) Entry Date(s): Date Created: 20191031 Date Completed: 20201019 Latest Revision: 20201019 Update Code: 20240513

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The Effect of Hapln4 Link Protein Deficiency on Extracellular Space Diffusion Parameters and Perineuronal Nets in the Auditory System During Aging.