The Effect of Hapln4 Link Protein Deficiency on Extracellular Space Diffusion Parameters and Perineuronal Nets in the Auditory System During Aging.
Aging
/ metabolism
Animals
Auditory Pathways
/ metabolism
Diffusion
Extracellular Matrix
/ metabolism
Extracellular Matrix Proteins
/ deficiency
Extracellular Space
/ metabolism
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins
/ deficiency
Organ Culture Techniques
Peripheral Nerves
/ metabolism
Protein Deficiency
/ metabolism
Trapezoid Body
/ metabolism
Aging
Diffusion
Extracellular matrix
Extracellular space
Hapln4
Journal
Neurochemical research
ISSN: 1573-6903
Titre abrégé: Neurochem Res
Pays: United States
ID NLM: 7613461
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
04
07
2019
accepted:
17
10
2019
revised:
30
09
2019
pubmed:
31
10
2019
medline:
21
10
2020
entrez:
31
10
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31664654
doi: 10.1007/s11064-019-02894-2
pii: 10.1007/s11064-019-02894-2
doi:
Substances chimiques
Extracellular Matrix Proteins
0
Hapln4 protein, mouse
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
68-82Subventions
Organisme : Grantová Agentura České Republiky
ID : 16-10214S
Organisme : Grant-in-Aid for Scientific Research on Innovative Areas
ID : 19H04754
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