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Altered Phenotype of the Vestibular Organ in GLAST-1 Null Mice

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Abstract

Various studies point to a crucial role of the high-affinity sodium-coupled glutamate aspartate transporter GLAST-1 for modulation of excitatory transmission as shown in the retina and the CNS. While 2–4-month-old GLAST-1 null mice did not show any functional vestibular abnormality, we observed profound circling behavior in older (7 months) animals lacking GLAST-1. An unchanged total number of otoferlin-positive vestibular hair cells (VHCs), similar ribbon numbers in VHCs, and an unchanged VGLUT3 expression in type II VHCs were detected in GLAST-1 null compared to wild-type mice. A partial loss of supporting cells and an apparent decline of a voltage-gated channel potassium subunit (KCNQ4) was observed in postsynaptic calyceal afferents contacting type I VHCs, together with a reduction of neurofilament- (NF200-) and vesicular glutamate transporter 1- (VGLUT1-) positive calyces in GLAST-1 null mice. Taken together, GLAST-1 deletion appeared to preferentially affect the maintenance of a normal postsynaptic/neuronal phenotype, evident only with increasing age.

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Abbreviations

GLAST-1:

glutamate aspartate transporter 1

VGLUT:

vesicular glutamate transporter

VHCs:

vestibular hair cells

SCs:

supporting cells

WT:

wild-type

sm :

saccular macula

um :

utricular macula

ca :

cristae ampullares

IHCs:

inner hair cells

OHCs:

outer hair cells

CNS:

central nervous system

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Acknowledgments

The authors would like to thank Karin Rohbock and Barbara Holz for technical assistance. S.P.S., C.F., L.R., H.L., and M.K. supported by the European Commission, Marie Curie Training Site HEARING (QLG3-CT-2001-60009) and the Deutsche Forschungsgemeinschaft DFG Kni 316/4-3; A.L. supported by NIH R01 DC 02058; W.S. supported by the Centre of Molecular Medicine, University of Cologne (CMMC) and the Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases, University of Cologne (CECAD).

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Authors and Affiliations

  1. Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany

    Sebastian P. Schraven, Christoph Franz, Lukas Rüttiger & Marlies Knipper

  2. Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), Regenerative Biology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany

    Hubert Löwenheim

  3. Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago (UIC), 808 S. Wood St., Chicago, IL, 60612, USA

    Anna Lysakowski

  4. Laboratory of Molecular Neuroscience, Faculty of Medicine, Centre of Molecular Medicine, Cologne (CMMC) and Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases, Cologne (CECAD); Institute of Biochemistry, University of Cologne, Zülpicher Str. 47a, 50674, Cologne, Germany

    Wilhelm Stoffel

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  1. Sebastian P. Schraven
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  2. Christoph Franz
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  3. Lukas Rüttiger
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  4. Hubert Löwenheim
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  6. Wilhelm Stoffel
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  7. Marlies Knipper
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Correspondence to Marlies Knipper.

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Sebastian P. Schraven and Christoph Franz are joint first authors.

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Schraven, S.P., Franz, C., Rüttiger, L. et al. Altered Phenotype of the Vestibular Organ in GLAST-1 Null Mice. JARO 13, 323–333 (2012). https://doi.org/10.1007/s10162-011-0311-2

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  • DOI: https://doi.org/10.1007/s10162-011-0311-2

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