Neurogenesis and astrogenesis contribute to vestibular compensation in the neurectomized adult cat: cellular and behavioral evidence

Neurogenesis occurs in some regions of the adult mammalian brain and gives rise to neurons integrated into functional networks. In pathological or postlesional conditions, neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after unilateral vestibular neurectomy in the adult cat. Here we report that in cats infused with an antimitotic drug, cytosine-[beta]-D arabinofuranoside (AraC), the number of GAD67 and GFAP immunoreactive cells is increased, despite the total mitotic activity blockade observed in the deafferented vestibular nuclei after unilateral vestibular neurectomy. At the behavioral level, recovery of posturo-locomotor function was drastically delayed, and no alteration of the horizontal spontaneous nystagmus was observed. These cellular and behavioral results suggest that reactive neurogenesis and astrogenesis might contribute highly to vestibular compensation in the adult cat, probably by accelerating the recovery of vestibular functions

Compensation vestibulaire et vieillissement

Le système vestibulaire possède une remarquable capacité d’autoréparation. La compensation vestibulaire, un modèle de plasticité post-lésionnelle du système nerveux central, se réfère à un ensemble de mécanismes endogènes de neuroplasticité dans les noyaux vestibulaires en réponse à des atteintes du système vestibulaire périphérique et sous-tendant la restauration fonctionnelle. Au cours du vieillissement, cette plasticité « homéostatique », bien que toujours présente, s’amenuise et s’accompagne de perturbations sensorimotrices et cognitives. Indépendamment de l’âge, la compensation vestibulaire peut être améliorée par la thérapie pharmacologique mais également par une rééducation fondée sur le renforcement des autres modalités sensorielles, telles que la vision ou la proprioception, mais aussi celui des composantes cognitive et motrice. Dans cet article, nous décrivons d’abord les mécanismes neurobiologiques de la compensation vestibulaire, puis nous discutons l’impact du vieillissement sur cette plasticité adaptative

SK Channels Modulation Accelerates Equilibrium Recovery in Unilateral Vestibular Neurectomized Rats

We have previously reported in a feline model of acute peripheral vestibulopathy (APV) that the sudden, unilateral, and irreversible loss of vestibular inputs induces selective overexpression of small conductance calcium-activated potassium (SK) channels in the brain stem vestibular nuclei. Pharmacological blockade of these ion channels by the selective antagonist apamin significantly alleviated the evoked vestibular syndrome and accelerated vestibular compensation. In this follow-up study, we aimed at testing, using a behavioral approach, whether the antivertigo (AV) effect resulting from the antagonization of SK channels was species-dependent or whether it could be reproduced in a rodent APV model, whether other SK channel antagonists reproduced similar functional effects on the vestibular syndrome expression, and whether administration of SK agonist could also alter the vestibular syndrome. We also compared the AV effects of apamin and acetyl-DL-leucine, a reference AV compound used in human clinic. We demonstrate that the AV effect of apamin is also found in a rodent model of APV. Other SK antagonists also produce a trend of AV effect when administrated during the acute phase of the vertigo syndrome. Conversely, the vertigo syndrome is worsened upon administration of SK channel agonist. It is noteworthy that the AV effect of apamin is superior to that of acetyl-DL-leucine. Taken together, these data reinforce SK channels as a pharmacological target for modulating the manifestation of the vertigo syndrome during APV

Cellular and Molecular Mechanisms of Vestibular Ageing

While age-related auditory deficits and cochlear alterations are well described, those affecting the vestibular sensory organs and more broadly the central vestibular pathways are much less documented. Although there is inter-individual heterogeneity in the phenomenon of vestibular ageing, common tissue alterations, such as losses of sensory hair cells or primary and secondary neurons during the ageing process, can be noted. In this review, we document the cellular and molecular processes that occur during ageing in the peripheral and central vestibular system and relate them to the impact of age-related vestibular deficits based on current knowledge

Adult neurogenesis promotes balance recovery after vestibular loss

International audienc

Thyroid Axis and Vestibular Physiopathology: From Animal Model to Pathology

A recent work of our group has shown the significant effects of thyroxine treatment on the restoration of postural balance function in a rodent model of acute peripheral vestibulopathy. Based on these findings, we attempt to shed light in this review on the interaction between the hypothalamic–pituitary–thyroid axis and the vestibular system in normal and pathological situations. Pubmed database and relevant websites were searched from inception through to 4 February 2023. All studies relevant to each subsection of this review have been included. After describing the role of thyroid hormones in the development of the inner ear, we investigated the possible link between the thyroid axis and the vestibular system in normal and pathological conditions. The mechanisms and cellular sites of action of thyroid hormones on animal models of vestibulopathy are postulated and therapeutic options are proposed. In view of their pleiotropic action, thyroid hormones represent a target of choice to promote vestibular compensation at different levels. However, very few studies have investigated the relationship between thyroid hormones and the vestibular system. It seems then important to more extensively investigate the link between the endocrine system and the vestibule in order to better understand the vestibular physiopathology and to find new therapeutic leads

Une nouvelle zone de neurogenèse fonctionnelle

En dehors de deux structures précises : la zone sous-granulaire et la zone sous-ventriculaire, le cerveau du mammifère adulte est considéré comme non neurogène, c’est-à-dire incapable de produire de nouveaux neurones. Cependant, les influences environnementales qui s’opposent à cette activité peuvent être mises entre parenthèses dans certaines conditions. C’est ce qui se passe lorsque l’on réalise une neurectomie vestibulaire unilatérale chez le chat adulte. Nos travaux révèlent en effet l’existence d’une neurogenèse réactionnelle dans les noyaux vestibulaires désafférentés situés dans le tronc cérébral. Plus étonnant encore, nous avons montré que cette prolifération cellulaire postlésionnelle était fonctionnelle et participait aux processus de restauration des fonctions posturolocomotrices

Plasticity of the histamine H 3 receptors after acute vestibular lesion in the adult cat

International audienceAfter unilateral vestibular neurectomy (UVN) many molecular and neurochemical mechanisms underlie the neurophysiological reorganizations occurring in the vestibular nuclei (VN) complex, as well as the behavioral recovery process. As a key regulator, the histaminergic system appears to be a likely candidate because drugs interfering with histamine (HA) neurotransmission facilitate behavioral recovery after vestibular lesion. This study aimed at analyzing the post-lesion changes of the histaminergic system by quantifying binding to histamine H 3 receptors (H 3 R; mediating namely histamine autoinhibition) using a histamine H 3 3 receptor agonist ([ H]N-α-methylhistamine). Experiments were done in brain sections of control cats (N = 6) and cats submitted to UVN and killed 1 (N = 6) or 3 (N = 6) weeks after the lesion. UVN induced a bilateral decrease in binding density of the agonist [ 3 H]N-α-methylhistamine to H 3 R in the tuberomammillary nuclei (TMN) at 1 week post-lesion, with a predominant down-regulation in the ipsilateral TMN. The bilateral decrease remained at the 3 weeks survival time and became symmetric. Concerning brainstem structures, binding density in the VN, the prepositus hypoglossi, the subdivisions of the inferior olive decreased unilaterally on the ipsilateral side at 1 week and bilaterally 3 weeks after UVN. Similar changes were observed in the subdivisions of the solitary nucleus only 1 week after the lesion. These findings indicate vestibular lesion induces plasticity of the histamine H 3 R, which could contribute to vestibular function recovery

Neurogenic potential of the vestibular nuclei and behavioural recovery time course in the adult cat are governed by the nature of the vestibular damage.

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology