L-Thyroxine Improves Vestibular Compensation in a Rat Model of Acute Peripheral Vestibulopathy: Cellular and Behavioral Aspects

Rastoldo, Guillaume; Marouane, Emna; Mahmoudi, Nada El; Péricat, David; Watabe, Isabelle; Lapotre, Agnes; Tonetto, Alain; López-Juárez, Alejandra; El-Ahmadi, Abdessadek; Caron, Philippe; Fraysse, Marie-José; Chabbert, Christian; Zwergal, Andreas; Tighilet, Brahim

doi:10.3390/cells11040684

Cited by 16 publications

(33 citation statements)

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“…Evidence of an antivertigo effect of T4 was previously shown in a model of vestibular disorder-induced through a unilateral surgical section of the UVN ( 8 ). The experimental model of vestibulopathy used in the current study differs from the UVN model in several aspects.…”

Section: Discussionmentioning

confidence: 69%

“…This suggests that a single administration of T4 is sufficient to induce the observed beneficial effect. Recently, a significant antivertigo effect of T4 administration in a model of a full section of the vestibular nerve (UVN) was demonstrated for an acute administration (1 injection for 4 days beginning immediately after UVN) of the compound at a dose of 10 μg/kg ( 8 ). In the present TTK model, T4 administration with the same dosage and route of administration (10 μg/kg i.p ) did not produce any significant antivertigo effect on the overall locomotor behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Deiodinases play an important role in regulating the action of thyroid hormones which they can activate or deactivate, and the action of thyroid hormones is therefore partly dependent on the expression of deiodinases in different tissues ( 29 , 34 ). The expression of the DIO2 enzyme that converts T4–T3 has been evidenced in tanycytes, astrocytic cells, and certain sensory neurons ( 35 ) and its expression has recently been shown for the first time in the vestibular nuclei ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

“…The third phase of the project corresponded to the study of a daily administration of T3 alone or in combination with TRIAC over 4 days starting from the same day of the excitotoxically-induced vestibular injury. Doses of 10 μg/kg of T4 and T3 were based on previous study showing neuroprotective effect of thyroid hormones in rat models of vestibulopathy ( 8 ), and in rodent models of stroke ( 13 , 14 ).…”

Section: Methodsmentioning

confidence: 99%

“…The antivertigo effect of levothyroxine (L-T4) was recently demonstrated in a rodent model of vestibulopathy induced by unilateral vestibular neurectomy (UVN) ( 8 ). In this model, acute L-T4 treatment accelerates the recovery of postural and locomotor functions in UVN rats.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Thyroid Hormones Antivertigo Effects in a Rat Model of Excitotoxically-Induced Vestibulopathy

Bringuier¹,

Hatat²,

Boularand³

et al. 2022

Front. Neurol.

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Impaired vestibular function induces disabling symptoms such as postural imbalance, impaired locomotion, vestibulo-ocular reflex alteration, impaired cognitive functions such as spatial disorientation, and vegetative deficits. These symptoms show up in sudden attacks in patients with Ménière or neuritis and may lead to emergency hospitalizations. To date, however, there is no curative solution to these pathologies and the effectiveness of treatments used to reduce symptoms in the management of patients is discussed. Thus, elucidating the biological mechanisms correlated to the expression kinetics of the vestibular syndrome is useful for the development of potential therapeutic candidates with a view to relieving patients and limiting emergency hospitalizations. Recently, a robust antivertigo effect of thyroxine (T4) was demonstrated in a rodent model of impaired vestibular function induced by unilateral surgical section of the vestibular nerve. The aim of the present study was to assess thyroid hormones L-T4 and triiodothyronine (T3) as well as the bioactive thyroid hormone metabolite TRIAC on a rodent model of acute unilateral vestibulopathy more representative of clinical vestibular pathology. To this end, a partial and transient unilateral suppression of peripheral vestibular inputs was induced by an excitotoxic lesion caused by transtympanic injection of kainic acid (TTK) into the inner ear of adult rats. Vestibular syndrome and functional recovery were studied by semi-quantitative and quantitative assessments of relevant posturo-locomotor parameters. In contrast to the effect previously demonstrated in the complete and irreversible vestibular injury model, administration of thyroxine in the TTK rodent model did not display significant antivertigo effect. However, it is noteworthy that administration of thyroxine showed trends to prevent posturo-locomotor alterations. Furthermore, the results of the current study suggested that a single dose of thyroxine is sufficient to induce the same effects on vestibular syndrome observed with sub-chronic administration, and that reducing the T4 dose may more efficiently prevent the appearance of vestibular deficits induced by the excitotoxic type lesion. Finally, comparison of the antivertigo effect of T4 in different vestibulopathy models enables us to determine the therapeutic indication in which thyroxine could be a potential therapeutic candidate.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%