Journal of neuroscience research
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Blast-induced neurotrauma (BINT) leads to deterioration at the cellular level, with adverse cognitive and behavioral outcomes. The nucleus accumbens (NAC) plays an important role in reward, addiction, aggression, and fear pathways. To identify the molecular changes and pathways affected at an acute stage in the NAC, this study focused on a time course analysis to determine the effects of blast on neurochemical and apoptotic pathways. ⋯ In addition, increased levels of caspase-3, an apoptotic marker, confirm active cell death in NAC. It is hypothesized that blast overpressure causes inflammation and neurochemical changes that trigger apoptosis in NAC. This cascade of events may lead to stress-related behavioral outcomes and psychiatric sequelae.
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Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. ⋯ The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.
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Brain-derived neurotrophic factor (BDNF) has critical functions in promoting survival, expansion, and differentiation of neural stem cells (NSCs), but its downstream regulation mechanism is still not fully understood. The role of BDNF in proliferation and differentiation of NSCs through Wnt/β-catenin signaling was studied via cell culture of cortical NSCs, Western blotting, immunocytochemistry, and TOPgal (Wnt reporter) analysis in mice. First, BDNF stimulated NSC proliferation dose dependently in cultured neurospheres that exhibited BrdU incorporation and neuronal and glial differentiation abilities. ⋯ Finally, an MEK inhibition experiment showed a mediating role of the microtubule-associated protein kinase pathway in BDNF-triggered Wnt/β-catenin signaling cascades. This study overall has revealed that BDNF might contribute to proliferation and neuronal and oligodendrocytic differentiation of NSCs in vitro, most possibly by triggering the Wnt/β-catenin signaling pathway. Nevertheless, determining the exact cross-talk points at which BDNF might stimulate Wnt/β-catenin signaling pathway in NSC activity requires further investigation.
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DL-2-Amino-4-phosphonobutyric acid (APB) is often used as a tool to block On pathways in studies of interactions between On and Off pathways in retinas. APB is an agonist of mGluR6 receptors and hyperpolarizes the On cone bipolar cells and rod bipolar cells. How APB affects Off responses of retinal ganglion cells (RGCs) in mouse retinas under dark and light adaptation is not clear. ⋯ Under light adaptation, APB decreased Off responses. Glycinergic and GABAergic antagonists did not prevent the APB-induced reduction of Off responses of RGCs; however, a dopaminergic type 1 receptor (D(1)) blocker (SCH 23390) and a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker (ZD 7288) prevented the APB-induced reduction of Off responses of RGCs under light adaptation. The results indicated afunctional circuit: On cone bipolar cells to Off cone bipolar cells via D(1) receptors and HCN channels.
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After traumatic brain injury (TBI), inflammation participates in both the secondary injury cascades and the repair of the CNS, both of which are influenced by the endocannabinoid system. This study determined the effects of repeated treatment with a cannabinoid type 2 receptor (CB(2) R) agonist on blood-brain barrier integrity, neuronal degeneration, and behavioral outcome in mice with TBI. We also looked for the presence of a prolonged treatment effect on the macrophage/microglial response to injury. ⋯ These changes in CCI mice treated with 0-1966 were associated with a prolonged reduction in macrophage/microglia cell counts. In conclusion, repeated treatments with a CB(2) R agonist, 0-1966, result in attenuated blood-brain barrier disruption and neuronal degeneration. In addition, repeated treatment with 0-1966 shows prolonged treatment effects on behavior and the macrophage/microglia cell response over several days.