A pilot study on early microgliogenesis following unilateral vestibular neurectomy: A key player in vestibular compensation?
Jessica TRICO, Emna MAROANE, Alain TONETTO, Isabelle WATABE, Agnes LAPOTRE & Brahim TIGHILET
Abstract:
Following unilateral vestibular damage, several behavioral deficits arise, referred to as vestibular syndrome. At the central level the vestibular syndrome is associated with an imbalance in neuronal activity between the two vestibular nuclei (VN). Its recovery is correlated with a rebalancing of the electrophysiological activity between both VN, known as vestibular compensation. Key plasticity mechanisms within the VN involved in this mechanism include, among others, neurogliogenesis, modulation of neuronal excitability and increased histamine release. In this study, we aimed to characterize the acute glial cell differentiation lineage in response to unilateral vestibular neurectomy (UVN) in the deafferented VN. We further assessed whether this response is influenced by the histaminergic system. To achieve this, betahistine dihydrochloride (BD), was used to stimulate histamine synthesis and release in the VN. After UVN, 2 animal groups were treated orally during 3 days with either BD treatment (UVN BD group, 50 mg/kg/day) or placebo (UVN placebo group). We present preliminary evidence of acute and abundant microgliogenesis restricted to the deafferented VN in both groups. This phenomenon does not appear to be mediated by BD treatment but may reflect an intrinsic biological adaptative mechanism. Further investigations, including Sholl analysis, would be essential to characterize microglia, which may represent a key player in vestibular compensation.
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Central and peripheral plasticity after chemical unilateral labyrinthectomy: Glial responses, calyces dynamics, and behavioral consequences
Jessica TRICO, Isabelle WATABE, Vinay PARAMESHWARAPPA, Agnes LAPOTRE, Louis GODAERT , Alain TONETTO, Christian CHABBERT, Andreas ZERGAL, Brahim TIGHILET.
Abstract:
Peripheral vestibular disorders are highly prevalent, but the underlying neurobiological mechanisms remain poorly understood, particularly regarding bilateral peripheral plasticity following unilateral injury. Using a rat model of chemical unilateral labyrinthectomy (cUL) (SHAM, n = 14; cUL, n = 20), we combined behavioral analyses, auditory assessments, immunohistochemistry, and histological quantification to characterize central and peripheral adaptations from 1 to 30 days after vestibular deafferentation. cUL induced significant postural deficits from day 1, while hyperactivity and anxiety-like behaviors emerged from day 9 and persisted over time. In the deafferented medial vestibular nucleus, robust glial reactivity developed rapidly (day 3) whereas only astrocytes remained significantly elevated throughout the observation period. Histological analyses revealed a marked loss of type I hair cell calyces in the ipsilateral utricle to ototoxic exposure at both acute (D3) and chronic (D30) time points. Unexpectedly, the contralateral utricle also exhibited a transient reduction in calyceal endings at D3 (p < 0.01), which recovered by D30, revealing previously unrecognized bilateral peripheral vestibular plasticity following unilateral vestibular injury. In contrast, cochlear alterations remained restricted to the ipsilateral side of ototoxic exposure indicating distinct adaptive responses in the auditory and vestibular organs. Together, these findings demonstrate that unilateral vestibular injury triggers coordinated central glial reactivity and contralateral peripheral vestibular plasticity, providing new insight into the cellular mechanisms underlying vestibular compensation.