Histamine H1 Receptor Contributes to Vestibular Compensation

Chen, ZP; Zhang, XY; Peng, SY; Yang, ZQ; Wang, YB; Zhang, YX; Chen, X; Wang, JJ; Zhu, JN

Wang, JJ; Zhu, JN (reprint author), Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, 163 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China.; Wang, JJ; Zhu, JN (reprint author), Nanjing Univ, Dept Physiol, Sch Life Sci, 163 Xianlin Ave,

JOURNAL OF NEUROSCIENCE, 2019; 39 (3): 420


Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.

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