Changes in TNFα, NFκB and MnSOD protein in the vestibular nuclei after unilateral vestibular deafferentation

Abstract

BackgroundUnilateral vestibular deafferentation results in strong microglial and astroglial activation in the vestibular nuclei (VN) that could be due to an inflammatory response. This study was aimed at determining if markers of inflammation are upregulated in the VN after chemical unilateral labyrinthectomy (UL) in the rat, and if the inflammatory response, if any, induces the expression of neuroprotective factors that could promote the plasticity mechanisms involved in the vestibular compensation process. The expressions of inflammatory and neuroprotective factors after chemical or mechanical UL were also compared to verify that the inflammatory response was not due to the toxicity of sodium arsanilate.MethodsImmunohistological investigations combined the labeling of tumor necrosis factor α (TNFα), as a marker of the VN inflammatory response, and of nuclear transcription factor κB (NFκB) and manganese superoxide dismutase (MnSOD), as markers of neuroprotection that could be expressed in the VN because of inflammation. Immunoreactivity (Ir) of the VN cells was quantified in the VN complex of rats. Behavioral investigations were performed to assess the functional recovery process, including both static (support surface) and dynamic (air-righting and landing reflexes) postural tests.ResultsChemical UL (arsanilate transtympanic injection) induced a significant increase in the number of TNFα-Ir cells in the medial and inferior VN on both sides. These changes were detectable as early as 4 h after vestibular lesion, persisted at 1 day, and regained nearly normal values at 3 days. The early increase in TNFα expression was followed by a slightly delayed upregulation of NFκB 8 h after chemical UL, peaking at 1 day, and regaining control values 3 days later. By contrast, upregulation of MnSOD was more strongly delayed (1 day), with a peak at 3 days, and a return to control values at 15 days. Similar changes of TNFα, NFκB, and MnSOD expression were found in rats submitted to mechanical UL. Behavioral observations showed strong posturo-locomotor deficits early after chemical UL (1 day) and a complete functional recovery 6 weeks later.ConclusionsOur results suggest that the upregulation of inflammatory and neuroprotective factors after vestibular deafferentation in the VN may constitute a favorable neuronal environment for the vestibular compensation process.

Modifications of perineuronal nets and remodelling of excitatory and inhibitory afferents during vestibular compensation in the adult mouse

“…Following UL, cellular and molecular changes have been also reported in the contralateral VN (Gacek and Schoonmaker 1997;Smith et al 1998;Gustave Dit Duflo et al 1999;Li et al 2002;Liberge et al 2010;Lacour 1998, 2001). Therefore, we asked whether vestibular compensation was accompanied by axonal plasticity in the contralateral LVN.…”

“…The measure of the support surface, namely the surface delimited by the four paws of the mouse while standing erect at rest, allows to evaluate the postural stability of the animal. Support surface is a very sensitive parameter used for evaluating static posture deficit and recovery after a vestibular lesion (Liberge et al 2010;Dutheil et al 2013). Mice were placed in a box equipped with a transparent bottom and filmed from below.…”

“…Dynamic postural deficits and recovery were evaluated in FVB mice (n = 6) by assessing the air-righting and the landing reflex (Liberge et al 2010). During the air-righting test, the mouse was held at approximately 40 cm above a cushion, in supine position.…”

“…Previous reports showed reactive neurogenesis and gliogenesis in the ipsilateral VN (De Waele et al 1996;Campos-Torres et al 1999Tighilet et al 2007;Lacour et al 2009), which play a role in functional recovery (Dutheil et al , 2013. Significant changes in the expression of brain-derived neurotrophic factor, choline acetyltransferase, GABA, neuroprotective factors, markers of inflammation and extracellular matrix molecules have been detected in the VN after peripheral damage (Smith et al 1998;Gustave Dit Duflo et al 1999;Lacour 1998, 2001;Lacour and Tighilet 2010;Liberge et al 2010;Deák et al 2012). …”

Une nouvelle zone de neurogenèse fonctionnelle

“…Ces résultats sont à rapprocher de données de la littérature mentionnant le rôle de ces facteurs respectifs dans la modulation des différentes étapes de la neurogenèse, allant de la prolifération des cellules souches neurales jusqu'à leur différencia-tion et intégration dans des circuits neuronaux complexes [8,[29][30][31]. D'autres facteurs actuellement en cours d'étude (facteurs de l'inflammation) également exprimés fortement dans les NV désafférentés [32] agiraient de concert pour promouvoir localement et ponctuellement un environnement neurogène dans les NV désafférentés.…”