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

Suchá, Petra; Chmelova, Martina; Kamenicka, Monika; Bochin, Marcel; Oohashi, Toshitaka; Vargová, Lýdia

doi:10.1007/s11064-019-02894-2

Cited by 14 publications

(16 citation statements)

References 54 publications

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“…Plasticity in the developing visual system is where much of our knowledge of PN function is derived from (see reviews Wlodarczyk et al, 2011;Wang and Fawcett, 2012). In the auditory system only a handful of studies have investigated the presence of PNs in the auditory brainstem, none of which examined the effect of old age on PN expression in the IC (Bertolotto et al, 1996;Hilbig et al, 2007;Foster et al, 2014;Sonntag et al, 2015;Beebe et al, 2016;Fader et al, 2016;Heusinger et al, 2019;Mansour et al, 2019;Sucha et al, 2019). Here we used the FBN rat, a recommended model for aging studies by the National Institute on Aging and determined that density of PNs increases with age in the IC.…”

Section: Comparison To Previous Studiesmentioning

confidence: 99%

The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

Mafi

Hofer

Russ

et al. 2020

Front. Aging Neurosci.

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Age-related hearing loss, one of the most frequently diagnosed disabilities in industrialized countries, may result from declining levels of GABA in the aging inferior colliculus (IC). However, the mechanisms of aging and subsequent disruptions of temporal processing in elderly hearing abilities are still being investigated. Perineuronal nets (PNs) are a specialized form of the extracellular matrix and have been linked to GABAergic neurotransmission and to the regulation of structural and synaptic plasticity. We sought to determine whether the density of PNs in the IC changes with age. We combined Wisteria floribunda agglutinin (WFA) staining with immunohistochemistry to glutamic acid decarboxylase in three age groups of Fischer Brown Norway (FBN) rats. The density of PNs on GABAergic and non-GABAergic cells in the three major subdivisions of the IC was quantified. Results first demonstrate that the density of PNs in the FBN IC increase with age. The greatest increases of PN density from young to old age occurred in the central IC (67% increase) and dorsal IC (117% increase). Second, in the young IC, PNs surround non-GABAergic and GABAergic cells with the majority of PNs surrounding the former. The increase of PNs with age in the IC occurred on both non-GABAergic and GABAergic populations. The average density of PN-surrounded non-GABAergic cells increased from 84.9 PNs/mm 2 in the young to 134.2 PNs/mm 2 in the old. While the density of PN-surrounded GABAergic cells increased from 26 PNs/mm 2 in the young to 40.6 PNs/mm 2 in the old. The causality is unclear, but increases in PN density in old age may play a role in altered auditory processing in the elderly, or may lead to further changes in IC plasticity.

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Section: Comparison To Previous Studiesmentioning

confidence: 99%

The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

Mafi

Hofer

Russ

et al. 2020

Front. Aging Neurosci.

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“…Studies in Hapln4-KO mice detected higher hearing thresholds at high frequencies and weaker temporal resolution ability in KO mice than in wild-type (WT) mice (Popelář et al, 2017). We have also reported the effect of HAPLN4 deficiency on extracellular diffusion parameters in MNTB during aging (Sucha et al, 2020). These results suggest the importance of HAPLN4 in auditory function.…”

Section: Introductionmentioning

confidence: 58%

“…In our previous reports, the diffuse expression of brevican in the MNTB of the young adult Hapln4-KO (aged 2-4 months) has been reported (Bekku et al, 2012;Sucha et al, 2020). However, the detailed spatial relationship of PNN components around the MNTB principal cells is lacking.…”

Section: Ectopic Expression Of Brevican In the Medial Nucleus Of The Trapezoid Body Of Hyaluronan And Proteoglycan Binding Link Protein 4mentioning

confidence: 92%

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

Nojima

Miyazaki

Hori

et al. 2021

Front. Cell Dev. Biol.

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The calyx of Held is a giant nerve terminal mediating high-frequency excitatory input to principal cells of the medial nucleus of the trapezoid body (MNTB). MNTB principal neurons are enwrapped by densely organized extracellular matrix structures, known as perineuronal nets (PNNs). Emerging evidence indicates the importance of PNNs in synaptic transmission at the calyx of Held. Previously, a unique differential expression of aggrecan and brevican has been reported at this calyceal synapse. However, the role of hyaluronan and proteoglycan binding link proteins (HAPLNs) in PNN formation and synaptic transmission at this synapse remains elusive. This study aimed to assess immunohistochemical evidence for the effect of HAPLN4 on differential PNN formation at the calyx of Held. Genetic deletion of Hapln4 exhibited a clear ectopic shift of brevican localization from the perisynaptic space between the calyx of Held terminals and principal neurons to the neuropil surrounding the whole calyx of Held terminals. In contrast, aggrecan expression showed a consistent localization at the surrounding neuropil, together with HAPLN1 and tenascin-R, in both gene knockout (KO) and wild-type (WT) mice. An in situ proximity ligation assay demonstrated the molecular association of brevican with HAPLN4 in WT and HAPLN1 in gene KO mice. Further elucidation of the roles of HAPLN4 may highlight the developmental and physiological importance of PNN formation in the calyx of Held.

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“…Hapln4 has been shown to be strongly expressed in normal human cortex, but its expression is decreased in high‐grade glioma samples (Sim, Hu, & Viapiano, 2009). Studies report an impact of Hapln4/Bral2 deficiency on extracellular space architecture and diffusion properties in several brain areas in HAPLN4 knockout mice (Cicanic et al., 2018; Sucha et al., 2020). Thus, the eQTL results presented here point to a rather complex scenario of potentially subtle ECM modifications comprising not only (if at all) the NCAN gene product itself but also a hyaluronan link protein and potentially also brevican as Hapln4 partner molecule in brain ECM perineuronal nets.…”

Section: Discussionmentioning

confidence: 99%

Neurocan genome‐wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans

Assmann

Richter

Schütze

et al. 2020

Eur J of Neuroscience

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Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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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

Cited by 14 publications

References 54 publications

The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

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

Neurocan genome‐wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans

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