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.

• MeSH
• corpus trapezoideum metabolismus   patologie   MeSH
• difuze * MeSH
• extracelulární matrix - proteiny nedostatek   MeSH
• extracelulární matrix metabolismus   patologie   MeSH
• extracelulární prostor metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• nedostatek proteinů metabolismus   patologie   MeSH
• orgánové kultury - kultivační techniky MeSH
• periferní nervy metabolismus   patologie   MeSH
• proteiny nervové tkáně nedostatek   MeSH
• sluchová dráha metabolismus   patologie   MeSH
• stárnutí metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Bral2 is a link protein stabilizing the binding between lecticans and hyaluronan in perineuronal nets and axonal coats (ACs) in specific brain regions. Using the real-time iontophoretic method and diffusion-weighted magnetic resonance, we determined the extracellular space (ECS) volume fraction (α), tortuosity (λ), and apparent diffusion coefficient of water (ADCW ) in the thalamic ventral posteromedial nucleus (VPM) and sensorimotor cortex of young adult (3-6 months) and aged (14-20 months) Bral2-deficient (Bral2-/- ) mice and age-matched wild-type (wt) controls. The results were correlated with an analysis of extracellular matrix composition. In the cortex, no changes between wt and Bral2-/- were detected, either in the young or aged mice. In the VPM of aged but not in young Bral2-/- mice, we observed a significant decrease in α and ADCW in comparison with age-matched controls. Bral2 deficiency led to a reduction of both aggrecan- and brevican-associated perineuronal nets and a complete disruption of brevican-based ACs in young as well as aged VPM. Our data suggest that aging is a critical point that reveals the effect of Bral2 deficiency on VPM diffusion. This effect is probably mediated through the enhanced age-related damage of neurons lacking protective ACs, or the exhausting of compensatory mechanisms maintaining unchanged diffusion parameters in young Bral2-/- animals. A decreased ECS volume in aged Bral2-/- mice may influence the diffusion of neuroactive substances, and thus extrasynaptic and also indirectly synaptic transmission in this important nucleus of the somatosensory pathway.

• MeSH
• agrekany metabolismus   MeSH
• analýza rozptylu MeSH
• difuzní magnetická rezonance MeSH
• extracelulární matrix - proteiny nedostatek   genetika   MeSH
• extracelulární prostor diagnostické zobrazování   genetika   MeSH
• gangliová stimulancia farmakologie   MeSH
• kvartérní amoniové sloučeniny farmakologie   MeSH
• messenger RNA MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• neurony cytologie   účinky léků   MeSH
• novorozená zvířata MeSH
• proteiny nervové tkáně nedostatek   genetika   MeSH
• stárnutí fyziologie   MeSH
• techniky in vitro MeSH
• thalamus cytologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Brain-specific link protein Bral2 represents a substantial component of perineuronal nets (PNNs) enwrapping neurons in the central nervous system. To elucidate the role of Bral2 in auditory signal processing, the hearing function in knockout Bral2(-/-) (KO) mice was investigated using behavioral and electrophysiological methods and compared with wild type Bral2(+/+) (WT) mice. The amplitudes of the acoustic startle reflex (ASR) and the efficiency of the prepulse inhibition of ASR (PPI of ASR), produced by prepulse noise stimulus or gap in continuous noise, was similar in 2-week-old WT and KO mice. Over the 2-month postnatal period the increase of ASR amplitudes was significantly more evident in WT mice than in KO mice. The efficiency of the PPI of ASR significantly increased in the 2-month postnatal period in WT mice, whereas in KO mice the PPI efficiency did not change. Hearing thresholds in 2-month-old WT mice, based on the auditory brainstem response (ABR) recordings, were significantly lower at high frequencies than in KO mice. However, amplitudes and peak latencies of individual waves of click-evoked ABR did not differ significantly between WT and KO mice. Temporal resolution and neural adaptation were significantly better in 2-month-old WT mice than in age-matched KO mice. These results support a hypothesis that the absence of perineuronal net formation at the end of the developmental period in the KO mice results in higher hearing threshold at high frequencies and weaker temporal resolution ability in adult KO animals compared to WT mice.

• MeSH
• akustická stimulace metody   MeSH
• časové faktory MeSH
• extracelulární matrix - proteiny nedostatek   MeSH
• fyziologická adaptace fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši kmene 129 MeSH
• myši knockoutované MeSH
• myši MeSH
• nervová síť růst a vývoj   metabolismus   MeSH
• periferní nervy růst a vývoj   metabolismus   MeSH
• prepulsní inhibice fyziologie   MeSH
• proteiny nervové tkáně nedostatek   MeSH
• sluchové kmenové evokované potenciály fyziologie   MeSH
• úleková reakce fyziologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chronická bolest MeSH
• diferenciální diagnóza MeSH
• Ehlersův-Danlosův syndrom * MeSH
• extracelulární matrix - proteiny * nedostatek   MeSH
• klinické zkoušky jako téma MeSH
• kolagen MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• nervová tkáň patofyziologie   MeSH
• neuralgie * etiologie   MeSH
• nociceptivní bolest MeSH
• statistika jako téma MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH