Effects of unilateral cochlea ablation on the distribution of calretinin mRNA and immunoreactivity in the guinea pig ventral cochlear nucleus

Abstract

The predominantly neuronal, calcium-binding protein calretinin is highly expressed in the guinea pig auditory system. Within the ventral cochlear nucleus (VCN), calretinin-positive auditory nerve fibers terminate on many calretinin-containing bushy, octopus, and multipolar cells. The abundance of calretinin in the cochlear nucleus provides an ideal system for examining the effects of altered neuronal input on the expression of this calcium-binding protein. The present experiments examined the effects of unilateral cochlea ablation on calretinin immunoreactivity and mRNA levels in the VCN. Calretinin mRNA was labeled by in situ hybridization histochemistry using a radioactive oligonucleotide probe and was quantified by optical density measures on autoradiograms. Survival times of 1, 7, and 56 days postlesion were examined. The results revealed a consistent increase in calretinin mRNA in the rostral portion of the ipsilateral anterior VCN 1 day postlesion but no effect on calretinin mRNA in this region at 7 and 56 days postlesion. The intensity of immunohistochemical label was also increased at 1 and 7 days after surgery. In contrast, calretinin mRNA was not affected 1 day postlesion in the ipsilateral posterior VCN but was decreased at both 7 and 56 days postlesion. The decrease in calretinin mRNA in the posterior VCN at longer survival times was accompanied by decreased immunolabeling of fibers projecting from VCN cells to the superior olivary complex. These results suggest that calretinin gene expression is regulated in part by auditory nerve activity in some cochlear neurons but that additional factors related to the unique cellular milieu also control calretinin expression.

Temporal Changes of the Calcium-binding Proteins in the Medial Vestibular Nucleus following Unilateral Labyrinthectomy in Rats

“…The pattern of the changes in calretinin expression was similar to the recovery process of the static vestibular symptoms and the expressions of the c-Fos protein and pERK during vestibular compensation in rats (Kim et al, 2002(Kim et al, , 2004. Calretinin might play not only a complicated role in calcium regulation (Billing-Marczak & Kuanicki, 1999), but also in the response to the level of neuronal activity (Winsky & Jacobowitz, 1995): The up-regulation of calretinin by the neuronal activity may support the above notion.…”

Susceptibility of developing cochlear nucleus neurons to deafferentation-induced death abruptly ends just before the onset of hearing

“…Cytoplasmic calciumbinding proteins are thought to function as neuroprotective agents by buffering intracellular calcium (see Baim- bridge et al, 1992 for review). Following cochlear removal, Winsky and Jacobowitz (1995) have shown that calretinin is transiently elevated in adult CN neurons, possibly protecting these neurons from the excitotoxic effects of increased levels of intracellular free calcium known to accompany deafferentation . The developmental up-regulation of calcium-binding protein during early postnatal development of neurons in the CN may confer protection against deafferentation-induced neuron death.…”

Peripheral Cell Loss Related to Calcium Binding Protein Immunocytochemistry in the Dorsal Cochlear Nucleus in CBA/CaJ Mice during Aging

“…It has also been shown that calretinin immunoreactivity is more affected by lesions like cochlea ablation [Winsky and Jacobowitz, 1995]. Further support for the association of calretinin immunoreactivity with the sensory periphery comes from presynaptic calcium signaling in frog saccular hair cells that is regulated by calretinin [Edmonds et al, 2000].…”