Natural and lesion‐induced decrease in cell proliferation in the medial nucleus of the trapezoid body during hearing development

Abstract

The functional interactions between neurons and glial cells that are important for nervous system function are presumably established during development from the activity of progenitor cells. In this study we examined proliferation of progenitor cells in the medial nucleus of the trapezoid body (MNTB) located in the rat auditory brainstem. We performed DNA synthesis labeling experiments to demonstrate changes in cell proliferation activity during postnatal stages of development. An increase in cell proliferation correlated with MNTB growth and the presence of S100b-positive astrocytes among MNTB neurons. In additional experiments we analyzed the fate of newly born cells. At perinatal ages, newly born cells colabeled with the astrocyte marker S100b in higher numbers than when cells were generated at postnatal day 6. Furthermore, we identified newly born cells that were colabeled with caspase-3 immunohistochemistry and performed comparative experiments to demonstrate that there is a natural decrease in cell proliferation activity during postnatal development in rats, mice, gerbils, and ferrets. Lastly, we found that there is a stronger decrease in MNTB cell proliferation after performing bilateral lesions of the auditory periphery in rats. Altogether, these results identify important stages in the development of astrocytes in the MNTB and provide evidence that the proliferative activity of the progenitor cells is developmentally regulated. We propose that the developmental reduction in cell proliferation may reflect coordinated signaling between the auditory brainstem and the auditory periphery. J. Comp. Neurol. 522:971-985, 2014.

Defining the relationship between maternal care behavior and sensory development in Wistar rats: Auditory periphery development, eye opening and brain gene expression

“…This interpretation is consistent with results that showed higher vulnerability of P7 compared to P1 rats when exposed to hypoxia-ischemia, and with studies that tracked long-term maternal behavioral, learning and auditory deficits in rats exposed to perinatal anoxia at birth [16,48,49]. The first postnatal week in the rat auditory system represents a sensitive period for cell proliferation and for the development of a highly demanding metabolic profile [50][51][52]. Since Hif1a and Epas1 code for proteins that regulate the expression of multiple genes involved in glycolysis and angiogenesis, it can be predicted that changes in the expression of enzymes, transporters and pro-angiogenic factors such as VEGF, could begin before hearing onset, as has been documented in the superior olivary complex of gerbils for metabolic markers [53].…”

Glial Cell Expansion Coincides with Neural Circuit Formation in the Developing Auditory Brainstem

“…C; P < 0.01). Since neurons are not undergoing apoptosis nor proliferating during this time frame (Rodríguez‐Contreras et al, ; Saliu et al, ), the change in neuronal fraction reflects an increase in the total cell population of 26.3% (46.6% of P3 total cells = 36.9% of P6 total cells, so P6 total cells/ P3 total cells = 46.6/36.9, or a 26.3% increase). Oligodendrocyte‐lineage cells nearly doubled in percentage from P3 to P6 (15.8 vs. 29.0), which reflected more than a doubling in the ratio of total number P6/P3: 29.0% of 1.263/15.8% of 1 (normalized P3 number) = 2.32‐fold increase.…”

“…In a comprehensive study evaluating glial cells in the early postnatal MNTB, qualitative measurements found that immunofluorescent labeling of astrocytes and oligodendrocytes increases greatly during the first postnatal week, and labeling for microglia does not attain appreciable levels until after P6 (Dinh et al, ). A substantial number of non‐neuronal cells within the MNTB exhibit EdU incorporation during this time, about 30% of which become S100β + astrocytes (Saliu et al, ), but the extent to which oligodendrocytes contribute to this expansion in cell number is not known. The CH:MNTB system provides an opportunity to relate a quantitative picture of neuronal and glial cell numbers to key steps of synaptic growth and pruning.…”

Myelin development, plasticity, and pathology in the auditory system

“…The timeline for CNS myelin development in the mouse is comparable to what is observed in other rodents. For instance, in the rat and gerbil SOC, myelin gene expression and myelin protein immunoreactivity increase during the second to third postnatal week (Hafidi et al, ; Ehmann et al, ; Saliu et al, ).…”