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.

Department of Cellular Neurophysiology Institute of Experimental Medicine AS CR v v i Prague Czech Republic

Department of Molecular Biology and Biochemistry Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Neuroscience 2nd Faculty of Medicine Charles University 5 Úvalu 84 150 06 Prague 5 Czech Republic

Zobrazit více v PubMed

Trends Neurosci. 2010 Jun;33(6):259-66 PubMed

J Physiol. 1974 Apr;238(1):1-15 PubMed

IBRO Rep. 2016 Dec;1:54-60 PubMed

J Neurosci Res. 2018 Feb;96(2):313-327 PubMed

Brain. 2010 Aug;133(Pt 8):2331-47 PubMed

J Neurosci. 2006 Apr 19;26(16):4406-14 PubMed

Aging (Albany NY). 2017 Jun 28;9(6):1607-1622 PubMed

Cell Mol Life Sci. 2004 Aug;61(16):2031-45 PubMed

J Gen Physiol. 2010 Jun;135(6):583-94 PubMed

Philos Trans R Soc Lond B Biol Sci. 2014 Oct 19;369(1654):20140046 PubMed

Eur J Neurosci. 2008 Mar;27(6):1373-90 PubMed

Neuroscience. 1999;92(3):791-805 PubMed

PLoS One. 2011 Jan 31;6(1):e16666 PubMed

Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10116-21 PubMed

PLoS One. 2013 Jul 05;8(7):e68044 PubMed

J Neurochem. 2018 Dec;147(6):748-763 PubMed

Hum Brain Mapp. 2005 Aug;25(4):391-401 PubMed

J Biol Chem. 2003 Oct 17;278(42):41205-12 PubMed

Neuropathol Appl Neurobiol. 2004 Aug;30(4):338-50 PubMed

J Neurosci Methods. 1993 Jul;48(3):199-213 PubMed

J Biol Chem. 2003 Jun 6;278(23):21083-91 PubMed

Exp Gerontol. 1998 Nov-Dec;33(7-8):837-51 PubMed

Pflugers Arch. 2004 May;448(2):248-58 PubMed

Front Neural Circuits. 2014 Jul 29;8:83 PubMed

J Physiol. 1981 Dec;321:225-57 PubMed

J Physiol. 2015 Oct 1;593(19):4341-60 PubMed

Eur J Neurosci. 2005 Oct;22(8):1873-80 PubMed

J Neurocytol. 1983 Aug;12(4):697-712 PubMed

Hear Res. 2015 Nov;329:21-32 PubMed

Eur J Neurosci. 2012 Jul;36(1):2017-24 PubMed

PLoS One. 2014 Nov 26;9(11):e113444 PubMed

Physiol Res. 2017 Nov 24;66(5):867-880 PubMed

Glia. 1999 Oct;28(1):40-8 PubMed

Neuroscience. 2016 May 26;323:170-82 PubMed

Front Neuroanat. 2014 Jan 08;7:53 PubMed

J Comp Neurol. 2006 Feb 1;494(4):559-77 PubMed

Physiol Rev. 2008 Oct;88(4):1277-340 PubMed

Acta Neuropathol. 2013 Feb;125(2):215-29 PubMed

Mol Cell Neurosci. 2003 Sep;24(1):148-59 PubMed

J Neurophysiol. 1993 Nov;70(5):2035-44 PubMed

J Comp Neurol. 2012 Jun 1;520(8):1721-36 PubMed

Pharmacol Ther. 2013 Sep;139(3):313-26 PubMed

Adv Exp Med Biol. 2015;821:11-7 PubMed

J Biol Chem. 2006 Jun 30;281(26):17789-800 PubMed

Cell Tissue Res. 2006 Nov;326(2):311-37 PubMed

Nat Rev Neurosci. 2019 Aug;20(8):451-465 PubMed

Exp Neurol. 2015 Dec;274(Pt B):134-44 PubMed

eNeuro. 2018 Nov 14;5(5): PubMed

Hear Res. 2018 Sep;367:32-47 PubMed

Mol Neurobiol. 2016 Jan;53(1):73-82 PubMed

J Neurochem. 2010 Sep 1;114(5):1447-59 PubMed

J Neurosci. 2010 Feb 24;30(8):3113-23 PubMed

Hippocampus. 2002;12(2):269-79 PubMed

Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry

ALS-like pathology diminishes swelling of spinal astrocytes in the SOD1 animal model

A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke

Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held