Impact of sound exposure and aging on brain-derived neurotrophic factor and tyrosine kinase B receptors levels in dorsal cochlear nucleus 80 days following sound exposure

Abstract

Recent studies suggested that acute sound exposure resulting in a temporary threshold shift in young adult animals within a series of maladaptive plasticity changes in central auditory structures. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in post-trauma peripheral hair cell and spiral ganglion cell survival and has been shown to modulate synaptic strength in cochlear nucleus following sound exposure. The present study evaluated levels of BDNF and its receptor (tyrosine kinase B, [TrkB]) in the dorsal cochlear nucleus (DCN) following a unilateral moderate sound exposure in young (7–8 months) and aged (28–29 months) Fischer Brown Norway (FBN) rats. Eighty days post-exposure, ABR thresholds for young exposed rats approached control values while aged exposed rats showed residual permanent threshold shifts relative to aged controls. BDNF protein levels were significantly up-regulated by 9% in young exposed fusiform cells ipsilateral to the exposure. BDNF levels in aged sound-exposed fusiform cells increased 31% ipsilateral to the exposure. Protein levels of the BDNF receptor, TrkB, were also significantly increased in aged but not in young sound-exposed DCN fusiform cells. The present findings suggest a relationship between the up-regulation of BDNF/TrkB and the increase in spontaneous and driven activity previously observed for aged and sound-exposed fusiform cells. This might be due to a selective maladaptive compensatory down-regulation of glycinergic inhibition in DCN fusiform cells.

The FBN rat model of aging: investigation of ABR waveforms and ribbon synapse changes

“…The present study was carried out in the NIA supplied FBN F1 hybrid strain [F344 × Brown Norway (F344BN)] which has a long life span with 50% mortality at 36m of age (Lipman, Chrisp et al 1996, Lipman 1997). This strain has been extensively used in studies of central auditory aging and has been compared with other rat models of aging (Milbrandt and Caspary 1995, Caspary, Holder et al 1999, Caspary, Schatteman et al 2005, Ling, Hughes et al 2005, Turner and Caspary 2005, Turner, Hughes et al 2005, Caspary, Hughes et al 2006, Caspary, Ling et al 2008, Schatteman, Hughes et al 2008, Wang, Turner et al 2009, de Villers-Sidani, Alzghoul et al 2010, Hughes, Turner et al 2010, Richardson, Ling et al 2011, Wang, Brozoski et al 2011, Richardson, Ling et al 2013, Gold and Bajo 2014). The present study was driven by the need to better understand the relative timing and magnitude of the impact of aging on the auditory peripheral in the FBN rat, a strain where the impact of age-related “hidden hearing loss” has been extensively described as a compensatory loss of inhibitory function at multiple levels of the CANS (Caspary, Ling et al 2008, Burianova, Ouda et al 2009, Richardson, Ling et al 2013).…”

Sensorial frailty: age-related hearing loss and the risk of cognitive impairment and dementia in later life

“…ARHL or noise-induced hearing loss may also result in cortical changes, [93][94][95][96][97][98] which could also affect cognitive functions localized in the affected brain regions. These included changes in excitatory, inhibitory and neuromodulatory networks, consistent with theories of homeostatic plasticity, [93][94][95][96][97] functional alterations in gene expression and in protein levels, 93,98 and broader network processing effects with cognitive and behavioral implications. 93 Sensory loss may be compensated also triggering neurovascular and neurophysiological changes, including cerebral blood flow dysregulation and disruption of the neurovascular unit and the blood-brain barrier, similar to those of dementia and leading to cognitive decline.…”

Brain-Derived Neurotrophic Factor Is Involved in Activity-Dependent Tonotopic Refinement of MNTB Neurons

“…We hypothesized that sound stimulation increases BDNF expression which enhances the structural and physiological plasticity of MNTB neurons. Sound stimulation has been shown to increase BDNF transcript and protein levels in the brainstem (Wang et al, 2011;Matt et al, 2018). In WT mice, sound stimulation (80 dB, 16 kHz, 3 h/day) from P13 to P19 increased mature BDNF protein by 25%, but not pro-BDNF, in the auditory brainstem (mature BDNF: p = 0.02, Welch's t-test, n = 3 per group; pro-BDNF: p = 0.40, Welch's t-test, n = 4/group; Figure 4A).…”

“…BDNF is a molecular mediator of neural activity-dependent plasticity shown in LTP of the hippocampus CA1 synapse (Korte et al, 1995;Patterson et al, 1996) and the visual cortex (Akaneya et al, 1997;Huber et al, 1998), as well as structural plasticity of myelin following increased sound input in humans and rats (Bengtsson et al, 2005;de Villers-Sidani et al, 2010). Within the auditory system, BDNF expression is dependent on sound-evoked activity shown with increased BDNF transcript and protein levels in the brainstem following sound stimulation (Wang et al, 2011;Matt et al, 2018). Here we found that at a pre-hearing age when peripheral sound input is not involved in recruiting BDNF, a global reduction of BDNF alters the AIS location of MNTB neurons and abnormally promotes tonotopic differences of AIS length and AP threshold.…”

“…By P14, BDNF mRNA expression is arranged tonotopically within the cochlea where expression is highest in the apical and medial turns, opposite of the NT3 mRNA expression gradient (Schimmang et al, 2003). Acoustic enrichment increases BDNF transcript levels and protein levels in rodent brainstem due to increased neuronal activity (Wang et al, 2011;Matt et al, 2018). Using anti-BDNF antibodies to neutralize BDNF signaling, activity-dependent plasticity of tonotopy following pure tone sound stimulation was prevented in the rat auditory cortex (Anomal et al, 2013).…”