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

Abstract

The expression of MAP2 (microtubule-associated protein 2) and of tyrosinated alpha-tubulin was investigated immunocytochemically in the cochleas of normal and amikacin-treated rats. For MAP2, two different antibodies were used: anti-MAP2ab, against the high molecular weight forms, and anti-MAP2abc, additionally against the embryonic form c. In the cochlea of the normal rat, the outer (OHCs) and inner (IHCs) hair cells were labeled for MAP2abc. The labeling was weaker in IHCs than in OHCs. The hair cells were rarely labeled for MAPab. Both OHCs and IHCs were labeled for tyrosinated alpha-tubulin. In the cochlea of the amikacin-treated rat, aggregates of anti-MAP2abc and anti-tyrosinated alpha-tubulin antibodies were seen in the apical region of the IHCs as early as the end of the antibiotic treatment. In rats investigated during the following week, the cell body of most of the surviving IHCs were not labeled for MAP2abc and tyrosinated alpha-tubulin. Then, labeling for these two antibodies reappeared in the surviving IHCs, including their giant stereocilia. Fewer surviving IHCs were labeled for tyrosinated alpha-tubulin than for MAP2abc. The amikacin-poisoned IHCs were rarely labeled for MAP2ab. These results suggest that cochlear hair cells essentially express form c of MAP2. In the amikacin-damaged cochlea, the apical aggregation of MAP2c and tyrosinated alpha-tubulin within the poisoned IHCs could be implicated in a cell degenerative process. By contrast, the extinction and recovery of MAP2c and tyrosinated alpha-tubulin labeling in the remaining IHCs suggest the occurrence of a limited repair process. A possible role of MAP2 and tubulin in hair cell survival is discussed.

Cochlear efferents in developing adult and pathological conditions

“…Worthy of note is that noise exposure also shows a change in innervation patterns (i.e., efferent neurons reinnervate the IHCs) during synaptic repair (Puel et al 1998). Similar features of innervation have also been observed with aminoglycoside intoxication (Lenoir et al 1999;Ladrech and Lenoir 2002). It might be conjectured that the projection of efferent neurons onto the hair cells favors the activity-dependent stabilization of afferent neurons by regulating hair cell excitability.…”

Role of nonlinear localized Ca2+ pulses along microtubules in tuning the mechano–sensitivity of hair cells

“…In that respect the association of MAP2 with MTs is very desirable. The role of MAP2 in cochlear inner hair cells of rat was experimentally examined by Ladrech and Lenior (2002). The studies of the role of myosin VIIA motor in sensory hair cells (Todorov et al, 2001) also revealed that its interaction with calmodulin and MAP-2B is regulated by Ca 2+ ions, which also could be supplied by localized pulses conveyed by actin filaments as polyelectrolytes.…”

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

“…Among them, cytoskeletal plasticity, with proteins such as Microtubule-associated Proteins (MAPs) or activity-dependent cytoskeletal protein (Arg3.1, also known as Arc) represents an interesting molecular pathway to investigate (Ladrech et al, 2004; Panford-Walsh et al, 2008). MAP has been reported to play a key-role in several pathophysiological conditions in the cochlea, ranging from synaptic reorganization following noise overexposure in the cochlea (Ladrech et al, 2004), to reaction to aminoglycoside toxicity (Ladrech and Lenoir, 2002). Expression of several MAP isoforms (in particular the MAP2c isorform, known for its role during the development of neurons) appears to be tightly regulated during the repair processes that occur in primary auditory neurons after excitotoxic injury in the cochlea, as well as after cochlear intoxication by amikacin, one of the well-known ototoxic drug (Ladrech and Lenoir, 2002; Ladrech et al, 2004).…”

“…MAP has been reported to play a key-role in several pathophysiological conditions in the cochlea, ranging from synaptic reorganization following noise overexposure in the cochlea (Ladrech et al, 2004), to reaction to aminoglycoside toxicity (Ladrech and Lenoir, 2002). Expression of several MAP isoforms (in particular the MAP2c isorform, known for its role during the development of neurons) appears to be tightly regulated during the repair processes that occur in primary auditory neurons after excitotoxic injury in the cochlea, as well as after cochlear intoxication by amikacin, one of the well-known ototoxic drug (Ladrech and Lenoir, 2002; Ladrech et al, 2004). In this last case, the MAP pathway has been suggested to play a key role in the survival of the remaining damaged sensory cells (Ladrech and Lenoir, 2002).…”

“…Expression of several MAP isoforms (in particular the MAP2c isorform, known for its role during the development of neurons) appears to be tightly regulated during the repair processes that occur in primary auditory neurons after excitotoxic injury in the cochlea, as well as after cochlear intoxication by amikacin, one of the well-known ototoxic drug (Ladrech and Lenoir, 2002; Ladrech et al, 2004). In this last case, the MAP pathway has been suggested to play a key role in the survival of the remaining damaged sensory cells (Ladrech and Lenoir, 2002). Results obtained on animal models of salicylate-induced tinnitus demonstrated change of Arg3.1 and BDNF during salicylate treatment in auditory structures, reinforcing the interest of cytoskeleton proteins as potential targets of research for tinnitus (Panford-Walsh et al, 2008; Singer et al, 2008).…”