6533b824fe1ef96bd12801bc
RESEARCH PRODUCT
The quality of cortical network function recovery depends on localization and degree of axonal demyelination
Manuela CerinaVenu NarayananChristoph KleinschnitzThomas SeidenbecherThomas BuddeViktoria GudiHeinz WiendlTobias RuckSven G. MeuthAlexander M. HerrmannKerstin GöbelThiemo DaldrupMartin StangelThomas SkripuletzPetra EhlingHans-christian PapeStefan BittnerPatrick Meuthsubject
0301 basic medicinePathologymedicine.medical_specialtyImmunologyCentral nervous systemSensationMedizinSensory systemBiologyAdaptive ImmunityWhite matter03 medical and health sciencesBehavioral NeuroscienceCuprizoneMice0302 clinical medicineWhite matter lesionmedicineBiological neural networkAnimalsRemyelinationGray MatterPathologicalMyelin SheathCerebral CortexBehavior AnimalEndocrine and Autonomic SystemsMultiple sclerosisLysophosphatidylcholinesThalamocortical systemRecovery of Functionmedicine.diseaseWhite MatterElectrodes ImplantedMice Inbred C57BLGray matter lesion030104 developmental biologymedicine.anatomical_structureRemyelinationDemyelinationTonotopyNerve NetNeuroscience030217 neurology & neurosurgeryDemyelinating Diseasesdescription
AbstractMyelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not well understood. Current therapeutic strategies for ameliorating the course of such diseases usually focus on promoting remyelination, but the effectiveness of these approaches strongly depends on the timing in relation to the disease state. In this study, we sought to characterize the time course of sensory and behavioral alterations induced by de- and remyelination to establish a rational for the use of remyelination strategies. By taking advantage of animal models of general and focal demyelination, we tested the consequences of myelin loss on the functionality of the auditory thalamocortical system: a well-studied neuronal network consisting of both white and gray matter regions. We found that general demyelination was associated with a permanent loss of the tonotopic cortical organization in vivo, and the inability to induce tone-frequency-dependent conditioned behaviors, a status persisting after remyelination. Targeted, focal lysolecithin-induced lesions in the white matter fiber tract, but not in the gray matter regions of cortex, were fully reversible at the morphological, functional and behavioral level. These findings indicate that remyelination of white and gray matter lesions have a different functional regeneration potential, with the white matter being able to regain full functionality while cortical gray matter lesions suffer from permanently altered network function. Therefore therapeutic interventions aiming for remyelination have to consider both region- and time-dependent strategies.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-03-12 |