Presbyacusis and Neurotrophic Factors

Doi Katsumi, Sato Takashi

doi:10.11289/otoljpn.20.203

Neurotrophic factors are naturally-occurring proteins that are released by neuronal target tissues to regulate neuronal survival and differentiation during development, and also essential for maintenance of neurons and neural circuitry throughout adulthood. The Neurotrophins (BDNF; Brain-derived neurotrophic factor, NT-3; Neurotrophin-3), FGF (Fibrocyte growth factor), and Insulin/IGF (Insulin-like growth factor)-1 have been indicated to play an important role in the auditory system, and can support SGN (Spiral ganglion neurons)/HC (Hair cells) survival following injury and in the ageing process.<br>We investigated the auditory system in the mice in which Klotho and p75^NRT genes were modified (Klotho mouse and p75^NRT mouse). In ageing Klotho mouse, EP (Endocochlear potential) depression, ABR (Auditory brainstem response) threshold's elevation, and SGC number's decrease were confirmed, suggesting that Klotho protein could act as a surviving and anti-ageing factor in the mouse auditory system. In ageing p75^NRT mouse, ABR threshold's elevation and SGC/HC number's decrease were confirmed, suggesting that p75^NRT could also act as an anti-ageing factor there.<br>Current understandings of Klotho and p75NTR insist that Klotho can serve as a cofactor essential for interactions between FGF (Fibroblast growth factor) 23 and FGF receptors and that p75NTR can serve as a lowaffinity receptor for BDNF and NT-3. These results indicate that the neurotrophins such as BDNF, NT-3, and FGF are required throughout life for the maintenance of the mouse auditory system.

Presbyacusis and Neurotrophic Factors

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