Neuroscience
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We recently indicated that brain-derived neurotrophic factor (BDNF) enhances the excitability of small-diameter trigeminal ganglion (TRG) neurons projecting onto the trigeminal nucleus interpolaris/caudalis (Vi/Vc) transition zone via a paracrine mechanism following masetter muscle (MM) inflammation. The present study investigated whether modulation of voltage-gated potassium (K) channels by BDNF contributes to this hyperexcitability effect. To induce inflammation we injected complete Freund's adjuvant (CFA) into the MM. ⋯ Furthermore, co-administration of K252a, a tyrosine kinase inhibitor, abolished the suppression of IA and IK currents by BDNF. These results suggested that the inhibitory effects of BDNF on IA and IK currents in small-diameter TRG neurons projecting onto the Vi/Vc potentiate neuronal excitability, and in turn, contribute to MM inflammatory hyperalgesia. These findings support the development of voltage-gated K(+) channel openers and tyrosine kinase inhibitors as potential therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.
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Recent research has investigated the expression and secretion of neuropeptides by tumors, and the potential of these peptides to facilitate tumor growth and spread. In particular, substance P (SP) and its receptor NK1 have been implicated in tumor cell growth and evasion of apoptosis, although few studies have examined this relationship in vivo. The present study used both in vitro and in vivo models to characterize the role of SP in tumor pathogenesis. ⋯ An animal model of brain tumors using the same cell line was employed to assess the effect of Emend IV on tumor growth in vivo. Administration of Emend IV was found to decrease tumor volume and decrease cellular proliferation indicating that SP may play a role in tumor pathogenesis within the brain. We conclude that SP may provide a novel therapeutic target in the treatment of certain types of brain tumors, with further research required to determine whether the role of SP in cancer is tumor-type dependent.
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The postsynaptic density is an electron dense meshwork composed of a variety of molecules facilitating neuronal signal transmission. ProSAP2/Shank3 represents a crucial player at postsynaptic sites, assembling large multimeric platforms and anchoring numerous other molecules, thereby linking the functional synapse with the cytoskeleton. ProSAP2/Shank3 is also implicated in the pathogenesis of numerous diseases, including autism spectrum disorders. ⋯ Thus an interaction between ProSAP2 and Kvβ2 could have important roles at diverse cellular compartments and moreover during maturation stages. We report here on the direct protein-protein interaction of the postsynaptic density anchoring molecule ProSAP2 and the potassium channel subunit Kvβ2, initially identified in a yeast-two-hybrid-screen. Furthermore, we characterize this interaction at synapses using primary hippocampal neurons in vitro.