Anti-RPIA monoclonal antibody Made to order

The intrathecal administration of prostaglandin F2-alpha to conscious mice resulted in spontaneous agitation and touch-evoked agitation (allodynia) in the animals. The maximum allodynia induced by prostaglandin F2-alpha was observed at 10-15 min after intrathecal injection, and the response did not disappear by 120 min. Prostaglandin F2-alpha produced allodynia over a wide range of dosage from 0.1 pg to 2.5-mu-g/mouse. Dose dependency of prostaglandin F2-alpha for allodynia showed a skewed bell-shaped pattern, and the maximal allodynic effect was observed at 1.0-mu-g. This allodynia was dose-dependently relieved by alpha-1-adrenergic (methoxamine), alpha-2-adrenergic (clonidine), and A1-adenosine (RPIA) agonists. Clonidine was 1.5 orders of magnitude more potent than methoxamine in blocking prostaglandin F2-alpha-induced allodynia. The blockade by clonidine was dose-dependently reversed by the alpha-2-adrenergic antagonist yohimbine but not by the alpha-1-adrenergic antagonist prazosin. These results demonstrate that prostaglandin F2-alpha administered intrathecally induces allodynia in conscious mice and that the allodynia involves the alpha-2-adrenergic and A1-adenosine systems. Because this allodynia has a clear resemblance to the characteristics of chronic pain in patients with causalgia and reflex sympathetic dystrophy, prostaglandin F2-alpha may be involved in allodynia observed with these disorders.

The deleterious effects of aging on the brain remain to be fully elucidated. In the present study, proteomic changes of young (4-month) and aged (16-month) B6129SF2/J male mouse hippocampus and cerebral cortex were investigated by using nano liquid chromatography tandem mass spectrometry (NanoLC-ESI-MS/MS) combined with tandem mass tag (TMT) labeling technology. Compared with the young animals, 390 hippocampal proteins (121 increased and 269 decreased) and 258 cortical proteins (149 increased and 109 decreased) changed significantly in the aged mouse. Bioinformatic analysis indicated that these proteins are mainly involved in mitochondrial functions (FIS1, DRP1), oxidative stress (PRDX6, GSTP1, and GSTM1), synapses (SYT12, GLUR2), ribosome (RPIA, RPS3), cytoskeletal integrity, transcriptional regulation, and GTPase function. The mitochondrial fission-related proteins FIS1 and DRP1 were significantly increased in the hippocampus and cerebral cortex of the aged mice. Further results in the hippocampus showed that ATP content was significantly reduced in aged mice. A neurotrophin brain-derived neurotrophic factor (BNDF), a protein closely related with synaptic plasticity and memory, was also significantly decreased in the hippocampus of the aged mice, with the tendency of synaptic protein markers including complexin-2, synaptophysin, GLUR2, PSD95, NMDAR2A, and NMDAR1. More interestingly, 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA oxidative damage, increased as shown by immunofluorescence staining. In summary, we demonstrated that aging is associated with systemic changes involving mitochondrial dysfunction, energy reduction, oxidative stress, loss of neurotrophic factor, synaptic proteins, and ribosomal proteins, as well as molecular deficits involved in various physiological/pathological processes.