Lesion-induced changes of brevican expression in the perineuronal net of the superior vestibular nucleus

Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements,posture and vegetative functions.After a shorter or longer period of time,the vestibular function is partially or completely restored via a series of processes such as modification in the efficacy of synaptic inputs.As the plasticity of adult central nervous system is associated with the alteration of extracellular matrix,including its condensed form,the perineuronal net,we studied the changes of brevican expression in the perineuronal nets of the superior vestibular nucleus after unilateral labyrinth lesion.Our results demonstrated that the unilateral labyrinth lesion and subsequent compensation are accompanied by the changing of brevican staining pattern in the perineuronal nets of superior vestibular nucleus of the rat.The reduction of brevican in the perineuronal nets of superior vestibular nucleus may contribute to the vestibular plasticity by suspending the non-permissive role of brevican in the restoration of perineuronal net assembly.After a transitory decrease,the brevican expression restored to the control level parallel to the partial restoration of impaired vestibular function.The bilateral changing in the brevican expression supports the involvement of commissural vestibular fibers in the vestibular compensation.All experimental procedures were approved by the 'University of Debrecen–Committee of Animal Welfare'(approval No.6/2017/DEMAB) and the 'Scientific Ethics Committee of Animal Experimentation'(approval No.HB/06/éLB/2270-10/2017;approved on June 6,2017).

Modification of tenascin-R expression following unilateral labyrinthectomy in rats indicates its possible role in neural plasticity of the vestibular neural circuit

We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrin- thectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestib- ular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tena- scin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.

Microglia as hackers of the matrix:sculpting synapses and the extracellular space

Microglia shape the synaptic environment in health and disease,but synapses do not exist in a vacuum.Instead,pre-and postsynaptic terminals are surrounded by extracellular matrix(ECM),which together with glia comprise the four elements of the contemporary tetrapartite synapse model.While research in this area is still just beginning,accumulating evidence points toward a novel role for microglia in regulating the ECM during normal brain homeostasis,and such processes may,in turn,become dysfunctional in disease.As it relates to synapses,microglia are reported to modify the perisynaptic matrix,which is the diffuse matrix that surrounds dendritic and axonal terminals,as well as perineuronal nets(PNNs),specialized reticular formations of compact ECM that enwrap neuronal subsets and stabilize proximal synapses.The interconnected relationship between synapses and the ECM in which they are embedded suggests that alterations in one structure necessarily affect the dynamics of the other,and microglia may need to sculpt the matrix to modify the synapses within.Here,we provide an overview of the microglial regulation of synapses,perisynaptic matrix,and PNNs,propose candidate mechanisms by which these structures may be modified,and present the implications of such modifications in normal brain homeostasis and in disease.