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In this study, we observed the effects of lipopolysaccharide (LPS) on neurodegeneration and immune response in the hippocampus. LPS is a gram-negative bacterial cell surface proteoglycan and known as a bacterial endotoxin. For this, we investigated the optimal concentration of LPS influencing the ICR mouse hippocampus to measure the LPS receptor, e.g., toll-like receptor 4 (TLR4), expression in mouse hippocampal homogenates. TLR4 expression was significantly and prominently increased in the hippocampal homogenates of the LPS (1 mg/kg)-treated group. Next, we examined pro-inflammatory response in the hippocampus using cyclooxygenase-2 (COX-2, a marker for inflammatory response) immunohistochemistry after LPS treatment. COX-2 immunoreactivity was significantly increased in the endothelium of blood vessels in the hippocampus 6 h after LPS treatment, judging from double immunofluorescence study with platelet-derived endothelial cell adhesion molecule-1 (PECAM-1, a marker for endothelial cells): it decreased 12 h and disappeared 24 h after LPS treatment. In addition, the ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive ((+)) microglia were morphologically activated in the mouse hippocampus after LPS treatment. At 24 h after LPS treatment, Iba-1(+) microglia of activated forms were abundant in the hippocampus. However, NeuN (a neuron-specific soluble nuclear antigen)(+) neurons were not significantly changed in the hippocampus after LPS treatment. Fluoro-jade B (a marker for neuronal degeneration)(+) cells were not detected in the hippocampus at any time after LPS treatment. In addition, there were no significant differences in permeability of blood-brain barriers at any time points after LPS treatment. In brief, our results indicate that intraperitoneal administration of 1 mg/kg LPS effectively induces LPS receptor (TLR4) expression in the hippocampus, and the treatment increases corticosterone levels, inflammation in the blood vessels, and microglial activation in the hippocampus without any neuronal damage.

No abstract

Neurotrophin 4 (NT-4) belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB) receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF), because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

ABSTRACT. Previously, we observed that electroacupuncture (EA) at ST36 (Zusanli) and GV20 (Baihui) enhanced cell proliferation and neuroblast differentiation in the rat dentate gyrus. In this study, we investigated the possible mechanisms of EA in this effect. For this, we applied EA at ST36 and GV20 of Wistar rats (13-week-old) once a day for 3 weeks. Application of EA at these acupoints significantly increased the number of phosphorylated cyclic AMP response element-binding protein (pCREB)-immunoreactive cells in the dentate gyrus. In addition, EA significantly increased the levels of brain-derived neurotrophic factor (BDNF) and pCREB protein in the dentate gyrus. The administration of K252a, an inhibitor of BDNF receptor, significantly reduced cell proliferation in the subgranular zone of dentate gyrus. These results suggest that EA significantly increased neuroblast plasticity via pCREB and BDNF activation in the dentate gyrus.