Neuroplastin expression is essential for hearing and hair cell PMCA expression.

Autor: Lin X; Neurogenetics Laboratory, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Department Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany., Brunk MGK; Department System Physiology and Learning, AG CortXplorer, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany., Yuanxiang P; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany., Curran AW; Department System Physiology and Learning, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany., Zhang E; Institute of Medical Psychology, Otto-Von-Guericke University Magdeburg, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany., Stöber F; Department System Physiology and Learning, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany., Goldschmidt J; Department System Physiology and Learning, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Center for Behavioral Brain Sciences (CBBS), 39106, Magdeburg, Germany., Gundelfinger ED; Department Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Medical Faculty, Molecular Neuroscience, Otto-Von-Guericke University Magdeburg, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany.; Center for Behavioral Brain Sciences (CBBS), 39106, Magdeburg, Germany., Vollmer M; Department System Physiology and Learning, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Department of Otolaryngology-Head and Neck Surgery, Otto-Von-Guericke University Magdeburg, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany., Happel MFK; Department System Physiology and Learning, AG CortXplorer, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Center for Behavioral Brain Sciences (CBBS), 39106, Magdeburg, Germany., Herrera-Molina R; Department Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Centro Integrativo de Biología Y Química Aplicada, Universidad Bernardo O'Higgins, 8307993, Santiago, Chile.; Center for Behavioral Brain Sciences (CBBS), 39106, Magdeburg, Germany., Montag D; Neurogenetics Laboratory, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany. montag@lin-magdeburg.de.
Jazyk: angličtina
Zdroj: Brain structure & function [Brain Struct Funct] 2021 Jun; Vol. 226 (5), pp. 1533-1551. Date of Electronic Publication: 2021 Apr 12.
DOI: 10.1007/s00429-021-02269-w
Abstrakt: Hearing deficits impact on the communication with the external world and severely compromise perception of the surrounding. Deafness can be caused by particular mutations in the neuroplastin (Nptn) gene, which encodes a transmembrane recognition molecule of the immunoglobulin (Ig) superfamily and plasma membrane Calcium ATPase (PMCA) accessory subunit. This study investigates whether the complete absence of neuroplastin or the loss of neuroplastin in the adult after normal development lead to hearing impairment in mice analyzed by behavioral, electrophysiological, and in vivo imaging measurements. Auditory brainstem recordings from adult neuroplastin-deficient mice (Nptn -/- ) show that these mice are deaf. With age, hair cells and spiral ganglion cells degenerate in Nptn -/- mice. Adult Nptn -/- mice fail to behaviorally respond to white noise and show reduced baseline blood flow in the auditory cortex (AC) as revealed by single-photon emission computed tomography (SPECT). In adult Nptn -/- mice, tone-evoked cortical activity was not detectable within the primary auditory field (A1) of the AC, although we observed non-persistent tone-like evoked activities in electrophysiological recordings of some young Nptn -/- mice. Conditional ablation of neuroplastin in Nptn lox/loxEmx1Cre mice reveals that behavioral responses to simple tones or white noise do not require neuroplastin expression by central glutamatergic neurons. Loss of neuroplastin from hair cells in adult Nptn Δlox/loxPrCreERT mice after normal development is correlated with increased hearing thresholds and only high prepulse intensities result in effective prepulse inhibition (PPI) of the startle response. Furthermore, we show that neuroplastin is required for the expression of PMCA 2 in outer hair cells. This suggests that altered Ca 2+ homeostasis underlies the observed hearing impairments and leads to hair cell degeneration. Our results underline the importance of neuroplastin for the development and the maintenance of the auditory system.
Databáze: MEDLINE
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