PhD Scientific Days 2017

Oral Presentations: Neurosciences

Age-dependent hearing impairment in Caskin KO mice

Előadó neve

Humli, Viktória

Előadó munkahelye

Semmelweis University Department of Pharmacology and Pharmacotherapy / Institute of Experimental Medicine of the Hungarian Academy of Sciences, Laboratory of Drug Research

Előadó telefonszáma

+36202080888

Előadó e-mail címe

humli.viktoria@med.semmelweis-univ.hu

Az előadás címe

Age-dependent hearing impairment in Caskin KO mice

Szerző(k) neve és munkahelye

Viktória Humli 1,2; Judit Szepesy 3,1; István Gyertyán 1; Katalin Schlett 4; László Buday 5; Tibor Zelles 1
1 Semmelweis University Department of Pharmacology and Pharmacotherapy , Budapest
2 Institute of Experimental Medicine of the Hungarian Academy of Sciences, Laboratory of Drug Research, Budapest
3 Semmelweis University Department of Department of Otorhinolaryngology, Head and Neck Surgery, Budapest
4 Eötvös Loránd University Faculty of Science, Institute of Biology, Department of Physiology and Neurobiology, Budapest
5 Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzimology, Budapest

Szekció

Oral Presentations: Neurosciences

Data of the presenter

Doctoral School: János Szentágothai School of Neurosciences
Program: Functional Neurosciences
Supervisor: Tibor Zelles
E-mail address: humli.viktoria@med.semmelweis-univ.hu

Text of the abstract

Caskin is a multi-domain adaptor protein that binds to CASK (calcium/calmodulin-(CaM)-dependent serine kinase), a scaffold protein enriched in the mammalian central nervous system, particularly in synaptic areas. Caskin is expressed both pre- and postsynaptically. Its precise function is highly unexplored.
The sensory system seems to rely on Caskin, too. The presence of Caskin was shown in the retina, including the ribbon synapse. Hair cells in the hearing organ form contacts with their primary afferents by the means of ribbon synapses, which express CASK.
Our collaborators’, by using Caskin knock-out (KO) mice, explored the role of Caskin in dendritic spine formation and in cognition. The aim of my work was to decipher the function of Caskin in hearing.
We measured the hearing thresholds of 1.5 - 17.5 month old Caskin KO mice and their heterozygous (HZ) littermates at different frequences (4, 8, 16, 32 and 65 kHz) by auditory brainstem response (ABR). This evoked potential method tests the function of the inner ear and the auditory pathway in anesthetized mice and is suitable for several remasurements. To explore more subtle differences, we also performed detailed analysis of individual peaks (characterizing individual synaptic transmissions) of the ABR waves.
KO mice showed higher hearing thresholds, i.e., hearing impairment, compared to HZ littermates. The difference was more pronounced in older animals and on higher frequencies. The difference in the thresholds became statistically significant at the age of 6 months. The detailed analysis reveled the difference already at the age of 2.5 month. The amplitudes of peak I-V were significantly lower and the peak latencies were higher in the KO mice.
First in the literature, we have shown the age-dependent functional deterioration of hearing in Caskin KO mice. The lack of this protein causes age related hearing loss with an early onset and steep progression.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1047

Authors (legacy)

Viktória Humli 1,2; Judit Szepesy 3,1; István Gyertyán 1; Katalin Schlett 4; László Buday 5; Tibor Zelles 1
1 Semmelweis University Department of Pharmacology and Pharmacotherapy , Budapest
2 Institute of Experimental Medicine of the Hungarian Academy of Sciences, Laboratory of Drug Research, Budapest
3 Semmelweis University Department of Department of Otorhinolaryngology, Head and Neck Surgery, Budapest
4 Eötvös Loránd University Faculty of Science, Institute of Biology, Department of Physiology and Neurobiology, Budapest
5 Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Enzimology, Budapest