Acoustic trauma induces reemergence of the growth‐ and plasticity‐associated protein GAP‐43 in the rat auditory brainstem

Abstract

We explored the consequences of unilateral acoustic trauma to intracochlear and central nervous system structures in rats. An acoustic trauma, induced by applying click stimuli of 130 dB (sound pressure level; SPL) for 30 minutes, resulted in an instant and permanent threshold shift of 95.92 +/- 1.08 dB (SEM) in the affected ear. We observed, as a consequence, a structural deterioration of the organ of Corti. Deprivation-dependent changes of neurons of the auditory brainstem were determined using antibodies against neurofilament and the growth-associated protein GAP-43 and compared with those following cochleotomy, studied earlier. By 231 days posttrauma, spiral ganglion cell bodies and their processes were almost entirely lost from all cochlear regions with destroyed organ of Corti. In the lateral superior olive (LSO) ipsilateral to the trauma, cell bodies of lateral olivocochlear neurons turned transiently GAP-43 positive within the first 1.5 years posttrauma. The time course of emergence and disappearance of this population of neurons was similar to that found after cochleotomy. Additionally, after noise trauma, principal cells in contralateral LSO and in medial superior olive (MSO) on both sides of the brainstem developed an expression of GAP-43 that began 3 and 16 days posttrauma, respectively, and lasted for at least 1 year. Such cells were rarely observed after cochleotomy. An unequivocal rise in GAP-43 immunoreactivity was also found in the neuropil of the inferior colliculus and the ventral cochlear nucleus, both preferentially on the acoustically damaged side. We conclude that the degree and specific cause of sudden unilateral deafness entail specific patterns of plasticity responses in the auditory brainstem, possibly to prevent the neural network dedicated to locate sounds in the environment from delivering erroneous signals centralward.

Age Influences the Expression of GAP-43 in the Rat Hippocampus following Seizure

“…Likewise, multiple seizures induce GAP-43 mRNA expression in granule cells of the dentate gyrus of the rat [42]. A similar phenomenon of increased GAP-43 synthesis occurs after injury to the axons in peripheral neurons [43] or induction of GAP-43 after an acoustic trauma in rats [44]. We now report that a milder experimental intervention, i.e., a single, acute seizure episode, in young rats initially has a depressing effect on hippocampal GAP-43 rather than the increases reported by others [40,41].…”

Molecular Plasticity in the Rat Auditory Brainstem: Modulation of Expression and Distribution of Phosphoserine, Phospho-CREB and TrkB after Noise Trauma

“…When cochlear input is lost, this relocation might be related to the utilization of alternative sources of trophic support. The redistribution of TrkB in the cochlear nucleus we observed after traumatization happened at a time when GAP-43 expression increased as a consequence of acoustic overstimulation or cochleotomy [Illing et al, 1997;Michler and Illing, 2002]. Similarly, cervical axotomy of rubrospinal fibers in rats reduces the amount of TrkB mRNA and induces GAP-43 expression in rubrospinal neurons [Kobayashi et al, 1997].…”

“…BDNF is also able to modulate GAP-43 expression [de Groen et al, 1995;Gaiddon et al, 1996;Tongiorgi et al, 1997]. Changes in the distribution of these markers were put into relation to observations made earlier on the effects of unilateral deafening on the expression of GAP-43 [Illing, 2001;Michler and Illing, 2002].…”

Adaptation of Binaural Processing in the Adult Brainstem Induced by Ambient Noise

“…Studies investigating reversible longterm adaptation in the adult brainstem are rare. Moreover, most have used invasive techniques, such as cochlear ablation or acoustic traumata, to induce physiological and molecular changes in the brainstem of adult mammals (McAlpine et al, 1997;Suneja et al, 1998aSuneja et al, ,b, 2000Mossop et al, 2000;Potashner et al, 2000;Michler and Illing, 2002;Alvarado et al, 2004;Zhang et al, 2004) (for review, see Illing et al, 2000). Interestingly, studies in the auditory brainstem and midbrain indicate that deafening especially affects the inhibitory inputs (Suneja et al, 1998a,b;Vale and Sanes, 2002;Vale et al, 2003Vale et al, , 2004, although it is not clear whether these changes are due to neuronal cell death or reflect adaptation of the adult auditory brainstem to different auditory inputs in a potentially reversible manner.…”

“…One mechanism for short-term adaptation of binaural sensitivity is a differential shift in the synaptic weights of excitatory and inhibitory inputs to MSO and LSO via presynaptic GABA B receptor activation (Magnusson et al, 2008;Hassfurth et al, 2010). Most investigations of long-term adaptation of binaural sensitivity in the brainstem and midbrain have used invasive approaches, such as cochlear ablations or acoustic traumata (McAlpine et al, 1997;Suneja et al, 1998aSuneja et al, ,b, 2000Illing et al, 2000;Kaltenbach et al, 2000;Mossop et al, 2000;Potashner et al, 2000;Michler and Illing, 2002;Alvarado et al, 2004;Muly et al, 2004;Zhang et al, 2004). Studies investigating reversible long-term adaptation at early stages of the mammalian binaural system, however, are lacking.…”