Thermosensitive transient receptor potential vanilloid (TRPV) channels are widely expressed in the brain and known to profoundly influence Ca-signaling, neurotransmitter release and behavior. While these channels are expressed in the cerebellum, neuronal firing and hyperactivity/reflexes seem associated with cerebellar temperature modulation. However, the distribution and functional significance of TRPV-equipped elements in the cerebellum has remained unexplored. Among TRPV sub-family, TRPV3 is regulated by temperature within physiological range and its transcript highly expressed in the brain. The study aims at exploring the relevance of TRPV3 in the cerebellum of developing and adult rat. RT-PCR analysis showed expression of N- and C-terminal fragments of TRPV3 mRNA in the adult rat cerebellum. Using double immunofluorescence, TRPV3-immunoreactivity was observed in Calbindin D28K-labeled Purkinje neurons. The sections of cerebellum from the postnatal rats (P4, P8, P16 and P42) were processed for TRPV3-immunofluorescence. Compared to P4 and P8, the percent fluorescent area of TRPV3-immunoreactivity significantly increased in the cerebellum of P16 and P42 rats. With a view to test the significance of TRPV3 in cerebellar function, TRPV3-agonist (eugenol) or -inhibitors [ruthenium red or isopentenyl pyrophosphate (IPP)] were administered stereotaxically intra-cerebellum and motor responses analyzed. Compared to controls, rats injected with TRPV3 inhibitor significantly reduced the stride length (P < 0.001), locomotor activity (P < 0.001), and rotarod retention time (P < 0.001), but increased footprints length (P < 0.01) and escape latency (P < 0001). TRPV3-agonist treatment, however, had no effect on these behaviors. We suggest that TRPV3 in Purkinje neurons may serve as novel molecular component for Ca-signaling and motor coordination function of the cerebellum.
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http://dx.doi.org/10.1016/j.neuroscience.2019.10.047 | DOI Listing |
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