Neuroscience
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In some neurons, muscarinic M(1)-class receptors control L-type (Ca(V)1) Ca(2+)-channels via protein kinase C (PKC) or calcineurin (phosphatase 2B; PP-2B) signaling pathways. Both PKC and PP-2B pathways start with phospholipase C (PLC) activation. In contrast, P/Q- and N-type (Ca(V)2.1, 2.2, respectively) Ca(2+)-channels are controlled by M(2)-class receptors via G proteins that may act, directly, to modulate these channels. ⋯ However, PKC inhibitors (bisindolylmaleimide I and PKC-1936) only block modulation of currents through N and L types Ca(2+) channels; while the modulation of P/Q-type Ca(2+) channels remains unaffected. These results show that different branches of the same signaling cascade can be used to modulate different Ca(2+) channels. Finally, we found no evidence of calcineurin modulating these Ca(2+) channels during M(1)-receptor activation, although, in the same cells, we demonstrate functional PP-2B by activating dopaminergic D(2)-receptor modulation.
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Reg-2 is a secreted protein that is expressed de novo in motoneurons, sympathetic neurons, and dorsal root ganglion (DRG) neurons after nerve injury and which can act as a Schwann cell mitogen. We now show that Reg-2 is also upregulated by DRG neurons in inflammation with a very unusual expression pattern. In a rat model of monoarthritis, Reg-2 immunoreactivity was detected in DRG neurons at 1 day, peaked at 3 days (in 11.6% of DRG neurons), and was still present at 10 days (in 5%). ⋯ Changes in inflammation have previously been observed predominantly in the neuropeptide expressing, NGF responsive, DRG neurons. Our results show that changes also take place in the IB4 population, possibly driven by members of the LIF family of neuropoietic cytokines. In addition, the presence of Reg-2 in central axon terminals implicates Reg-2 as a possible modulator of second order dorsal horn cells.
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The mammalian hippocampus continues to generate new neurons throughout life. Experiences such as exercise, anti-depressants, and stress regulate levels of neurogenesis. Exercise increases adult hippocampal neurogenesis and enhances behavioral performance on rotarod, contextual fear and water maze in rodents. ⋯ Minimal changes in microglia associated with inflammation (using immunohistochemical detection of cd68) were detected at the time of behavioral testing. Irradiation did not reduce gains in performance on rotarod or contextual fear, however it eliminated gain in performance on the water maze. Results support the hypothesis that intact exercise-induced hippocampal neurogenesis is required for improved spatial memory, but not motor performance or contextual fear in C57BL/6J mice.