Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus

Abstract

During development, removal of neuronal input can lead to profound changes in postsynaptic cells, including atrophy and cell death. In the chicken brainstem cochlear nucleus, the nucleus magnocellularis (NM), deprivation of auditory input via unilateral cochlea removal or silencing the eighth nerve with tetrodotoxin leads to a loss of 25-30% of the neurons and the atrophy of surviving neurons. One intracellular component that may be involved in both cell atrophy and cell death is the cytoskeleton. The degradation of the cytoskeleton following deafferentation could potentially lead to either atrophy or death of NM neurons. However, little is known regarding the role of neuronal input on the cytoskeletal structure of NM neurons and whether changes in the cytoskeleton are responsible for cell death following deafferentation. The present study examined whether changes in the cytoskeleton of NM neurons occurred following cochlea removal. Several components of the cytoskeleton were analyzed following unilateral afferent deprivation. Levels of immunostaining for tubulin, actin, and microtubule-associated protein 2 (MAP-2), and levels of beta-tubulin and beta-actin mRNAs were assessed in NM neurons following cochlea removal. Our results revealed that afferent deprivation results in a rapid decrease in immunostaining for all three cytoskeletal proteins examined. These decreases were observed as early as 3 hours after cochlea removal and persisted for up to 4 days. In addition, these changes occurred in all deafferented NM neurons at the early time points, indicating that both dying and surviving NM neurons undergo a similar change in their cytoskeletons. In contrast to the decreases in immunostaining, levels of beta-tubulin and beta-actin mRNAs were not noticeably altered by deafferentation. Our findings indicate that the cytoskeleton is altered or degraded following deafferentation but that this process is not regulated at the transcriptional level.

Prenatal auditory enrichment with species‐specific calls and sitar music modulates expression of Bcl‐2 and Bax to alter programmed cell death in developing chick auditory nuclei

“…The expression of cytoskeletal proteins beta‐tubulin, beta‐actin and MAP‐2 in nm, is regulated by experimental manipulations like afferent deprivation (Kelly et al, 1997). Since the nm neurons undergo dynamic structural changes during normal development i.e.…”

Ear manipulations reveal a critical period for survival and dendritic development at the single‐cell level in Mauthner neurons

“…Therefore, it is also possible that these additional inputs stabilize the vestibular nucleus. Comparable to age related differential cell death (Lopez‐Otin et al, ), the causality for survival of some and death of other second‐order neurons following deafferentation remains unclear (Durham and Rubel, ; Steward and Rubel, ; Born and Rubel, ; Durham et al, ; Garden et al, ; Hyde and Durham, ,b; Garden et al, ; Kelley et al, )…”

Changes in MAP2 and tyrosinated α‐tubulin expression in cochlear inner hair cells after amikacin treatment in the rat

“…Instead, the transient changes in MAP2 and tubulin expression might contribute to the atrophy of the surviving hair cells. In support of this hypothesis, in acutely deprived cochlear nucleus neurons in the chicken, loss of MAP2, tubulin, and actin is associated with cell atrophy (Kelley et al, 1997). Moreover, according to these authors, this process may be part of a survival mechanism by decreasing the energy needs of the cells.…”

“…Mainly, the expression of MAP2 has been shown to coincide with neuritic outgrowth and branching during the period of development (Ferreira et al, 1990; Fisher et al, 1991), and at mature stage, MAP2 appeared to contribute to dendritic remodeling after lesions (Caceres et al, 1988). In the chicken cochlear nucleus, a decreased expression of MAP2 after afferent deprivation seemed to be involved in a cell survival mechanism (Kelley et al, 1997). In the cochlear spiral ganglion of the guinea pig, variations of MAP2 expression correlated with neuritic regrowth and neosynaptogenesis after excitotoxicity (Ladrech et al, 2001a).…”

“…The most important role of MAP2 is to stimulate microtubule assembly and enhance microtubular stability (Schoenfeld and Obar, 1994 for review). In the avian cochlear nucleus, a decrease of tubulin expression accompanied the decrease of MAP2 after afferent deprivation (Kelley et al, 1997). Moreover, alterations in tubulin distribution were noted in hair cells of the antibiotic‐poisoned guinea pig cochlea (Hackney et al, 1990; Leonova and Raphael, 1997).…”