Bee venom phospholipase A2 ameliorates motor dysfunction and modulates microglia activation in Parkinson's disease alpha-synuclein transgenic mice

α-Synuclein (α-Syn) has a critical role in microglia-mediated neuroinflammation, which leads to the development of Parkinson's disease (PD). Recent studies have shown that bee venom (BV) has beneficial effects on PD symptoms in human patients or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin-induced PD mice. This study investigated whether treatment with BV-derived phospholipase A2 (bvPLA2) would improve the motor dysfunction and pathological features of PD in human A53T α-Syn mutant transgenic (A53T Tg) mice. The motor dysfunction of A53T Tg mice was assessed using the pole test. The levels of α-Syn, microglia and the M1/M2 phenotype in the spinal cord were evaluated by immunofluorescence. bvPLA2 treatment significantly ameliorated motor dysfunction in A53T Tg mice. In addition, bvPLA2 significantly reduced the expression of α-Syn, the activation and numbers of microglia, and the ratio of M1/M2 in A53T Tg mice. These results suggest that bvPLA2 could be a promising treatment option for PD.

Neuroprotective Effects of AMP-Activated Protein Kinase on Scopolamine Induced Memory Impairment

AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate-induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons.

Effect of High-Dose Steroid Treatment on Adipogenesis and Secretion of PAI-1 in Rats / 대한정형외과연구학회지

This study was conducted to invetigate the effect of high-dose steroid administration on adipogenesis and secretion of PAI-1 in rat. Sixty healthy Wistar rats were divided into three groups. Group A consisted of 20 control animals received 5 ml/kg isotonic saline for 1 weeks. Group B consisted of 20 animals received 10 ml/kg of methylprednisolone intraperitoeally for 1 week. Group C comprized 20 animals received 10 ml/kg of methylprednisolone intraperitoneally for 1 week. After the completionof treatment, blood sampling was performed for measurenement of PAI-1 and the animale were sacrificed for histopathologic examination and immunohistochemical study. The PAI-1 protein expressin of femoral heads were evaluated with Western-blotting. Blood level of PAI-1 increased significantly in high-dose steroid treated group(Group B and C) compared to control group. In histopathologic examination, significant fat morrow conversion, fat cell hypertrophy and fat cyst formation were observed in high-dose steroid treated group. Immunohistochemically, PAi-1 expression was sprominent in the fat cells. Protein expression of PAI-1 of femoral heads increased significantly in highdose steroid treated group compared to control group. In lights of above results, it is postulated that increased secretion of PAI-1 from fat cells could play a major role in the pathogenesis of osteonecrosis of the femoral head in rats treated with high-dose steroid.