Behavioral Assessment of Vestibular Dysfunction in Rats

Maroto, Alberto F.; Greguske, Erin A.; Deulofeu, Meritxell; Fiol, Núria; Llorens, Jordi

doi:10.1007/978-1-0716-1637-6_9

Cited by 3 publications

(8 citation statements)

References 27 publications

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“…Vestibular deficient animals showed ataxia, spontaneous circling and head bobbing. The loss of function was assessed using high-speed video records of the tail-lift reflex as described (Martins-Lopes et al, 2019; Maroto et al, 2021a,c). A similar dose-dependent effect occurred in male and female animals, and therefore animals of both sexes were pooled for analyses.…”

Section: Resultsmentioning

confidence: 99%

“…To evaluate vestibular function, we assessed the tail-lift reflex as described (Martins-Lopes et al, 2019; Maroto et al, 2021a,c). Briefly, rats are held by the base of the tail and quickly but gently lifted upwards to approximately 40 cm above ground and immediately returned down.…”

Section: Methodsmentioning

confidence: 99%

“…Loss of vestibular function results in loss of the anti-gravity extension reflex, so the rat curls ventrally (Hunt et al, 1987; Pellis et al, 1991; Llorens et al, 1993; Maroto et al, 2021c). The reflex response of the animal is recorded from the side with high-speed video (we use 240 frames per second with a GoPro 5 camera) and the records are used to obtain the minimum angle formed by the nose, the back of the neck and the base of the tail during the tail-lift manoeuvre (tail-lift angle, TLA), as described (Martins-Lopes et al, 2019; Maroto et al, 2021a,c). The TLA has been demonstrated to provide an objective measure of permanent or reversible vestibular loss (Martins-Lopes et al, 2019; Maroto et al, 2021a,c).…”

Section: Methodsmentioning

confidence: 99%

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The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

Maroto

Borrajo

Callejo

et al. 2022

Preprint

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Hair cell (HC) loss by epithelial extrusion has been described to occur in the vestibular system of rats and mice during the chronic ototoxicity caused by 3,3’-iminodipropionitrile (IDPN). This is preceded by early dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals. In the present study, we evaluated whether these pathological phenomena have wider significance. First, we assessed their occurrence in rats receiving streptomycin for 3 to 8 weeks. Streptomycin caused a loss of vestibular function that was largely reversible and associated with a partial loss of HCI. In the calyces encasing the surviving HCI, we observed decreased expression of CASPR1 denoting calyceal junction dismantlement. We also recorded reduced numbers of pre-synaptic (ribeye) and post-synaptic (PSD95) puncta per cell, and KCNQ4 mislocalization. After washout, the CASPR1 label revealed calyceal junction rebuilding. Ultrastructural data also showed calyx junction dismantlement and calyx fragmentation. Limited but clear evidence for HC extrusion was obtained by scanning electron microscopy and immunofluorescent analysis. Second, we evaluated human sensory epithelia from therapeutic labyrinthectomy and trans-labyrinthine. In some of the samples, patched CASPR1 label indicated that a process of calyx junction dismantlement could be in progress. The present data supports the hypothesis that dismantlement of the calyceal junction is a common response triggered by chronic stress in the vestibular sensory epithelium. This effect precedes HC loss, is reversible, and may explain, at least in part, observations of reversion in function loss.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

Maroto

Borrajo

Callejo

et al. 2022

Preprint

Self Cite

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show abstract

“…To evaluate vestibular function, we assessed the tail-lift reflex as described (Martins-Lopes et al 2019 ; Maroto et al 2021a , c ). Briefly, rats are held by the base of the tail and quickly but gently lifted upwards to approximately 40 cm above ground and immediately returned down.…”

Section: Methodsmentioning

confidence: 99%

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

et al. 2023

Self Cite

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Hair cell (HC) loss by epithelial extrusion has been described to occur in the rodent vestibular system during chronic 3,3′-iminodipropionitrile (IDPN) ototoxicity. This is preceded by dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals. Here, we evaluated whether these phenomena have wider significance. First, we studied rats receiving seven different doses of streptomycin, ranging from 100 to 800 mg/kg/day, for 3–8 weeks. Streptomycin caused loss of vestibular function associated with partial loss of HCI and decreased expression of contactin-associated protein (CASPR1), denoting calyceal junction dismantlement, in the calyces encasing the surviving HCI. Additional molecular and ultrastructural data supported the conclusion that HC-calyx detachment precede HCI loss by extrusion. Animals allowed to survive after the treatment showed functional recuperation and rebuilding of the calyceal junction. Second, we evaluated human sensory epithelia obtained during therapeutic labyrinthectomies and trans-labyrinthine tumour excisions. Some samples showed abnormal CASPR1 label strongly suggestive of calyceal junction dismantlement. Therefore, reversible dismantlement of the vestibular calyceal junction may be a common response triggered by chronic stress, including ototoxic stress, before HCI loss. This may partly explain clinical observations of reversion in function loss after aminoglycoside exposure.

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“…Like human neurological exams, rodent observational batteries often serve as a first-tier test to identify “an effect.” Examples include the Functional Observational Battery ( US EPA, 1994b ; Moser and Kallman, 2018 ; Gauvin, 2021 ) and the SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA) ( Rogers et al, 2001 ; Lalonde et al, 2021 ). Additional batteries have been developed for assessing vestibular dysfunction ( Maroto et al, 2021 ), various genetic manipulations ( Brown et al, 2000 ), and neonatal function ( Fox, 1965 ; Brown et al, 2000 ; Feather-Schussler and Ferguson, 2016 ; Soria-Ortiz et al, 2021 ).…”

Section: Behavioral Assessmentsmentioning

confidence: 99%

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

Harry¹,

McBride²,

Witchey³

et al. 2022

Front. Toxicol.

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With the appreciation that behavior represents the integration and complexity of the nervous system, neurobehavioral phenotyping and assessment has seen a renaissance over the last couple of decades, resulting in a robust database on rodent performance within various testing paradigms, possible associations with human disorders, and therapeutic interventions. The interchange of data across behavior and other test modalities and multiple model systems has advanced our understanding of fundamental biology and mechanisms associated with normal functions and alterations in the nervous system. While there is a demonstrated value and power of neurobehavioral assessments for examining alterations due to genetic manipulations, maternal factors, early development environment, the applied use of behavior to assess environmental neurotoxicity continues to come under question as to whether behavior represents a sensitive endpoint for assessment. Why is rodent behavior a sensitive tool to the neuroscientist and yet, not when used in pre-clinical or chemical neurotoxicity studies? Applying new paradigms and evidence on the biological basis of behavior to neurobehavioral testing requires expertise and refinement of how such experiments are conducted to minimize variability and maximize information. This review presents relevant issues of methods used to conduct such test, sources of variability, experimental design, data analysis, interpretation, and reporting. It presents beneficial and critical limitations as they translate to the in vivo environment and considers the need to integrate across disciplines for the best value. It proposes that a refinement of behavioral assessments and understanding of subtle pronounced differences will facilitate the integration of data obtained across multiple approaches and to address issues of translation.

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Behavioral Assessment of Vestibular Dysfunction in Rats

Cited by 3 publications

References 27 publications

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

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