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Publication : A deficiency of the link protein Bral2 affects the size of the extracellular space in the thalamus of aged mice.

First Author  Cicanic M Year  2018
Journal  J Neurosci Res Volume  96
Issue  2 Pages  313-327
PubMed ID  28815777 Mgi Jnum  J:269955
Mgi Id  MGI:6275769 Doi  10.1002/jnr.24136
Citation  Cicanic M, et al. (2018) A deficiency of the link protein Bral2 affects the size of the extracellular space in the thalamus of aged mice. J Neurosci Res 96(2):313-327
abstractText  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 (alpha), tortuosity (lambda), 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 alpha 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.
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