A deficiency of the link protein Bral2 affects the size of the extracellular space in the thalamus of aged mice
Abstrakt
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 (), tortuosity (), and apparent diffusion coefficient of water (ADC(W)) 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 and ADC(W) 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.