Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats

Kód výsledku v IS VaVaI

RIV/68378041:_____/21:00551560 - isvavai.cz

Nalezeny alternativní kódy

RIV/00216208:11120/21:43920873

Výsledek na webu

https://www.sciencedirect.com/science/article/abs/pii/S037859552030410X?via%3Dihub

DOI - Digital Object Identifier

10.1016/j.heares.2020.108139

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats

Popis výsledku v původním jazyce

AUT0 0 063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K + channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on au-ditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic star-tle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug ad-ministration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT0 0 063 and AUT0 0202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT0 0 063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT0 0 063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT0 0 063 and AUT0 0202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.

Název v anglickém jazyce

Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats

Popis výsledku anglicky

AUT0 0 063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K + channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on au-ditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic star-tle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug ad-ministration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT0 0 063 and AUT0 0202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT0 0 063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT0 0 063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT0 0 063 and AUT0 0202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

GA18-09692S: Změny funkce sluchového systému ve spojitosti se zvukovou expozicí a věkem

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Hearing Research

ISSN

0378-5955

e-ISSN

1878-5891

Svazek periodika

401

Číslo periodika v rámci svazku

mar.

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

108139

Kód UT WoS článku

000632467500001

EID výsledku v databázi Scopus

2-s2.0-85097896615