Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the Hippocampus

Abstract

(Ϫ/Ϫ) mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor. Microinjecting the BDNF scavenger TrkB-Fc into the right ventricle before each PTZ treatment significantly suppressed the development of kindling in wild-type mice, whereas no effect was observed in MMP-9 (Ϫ/Ϫ) mice. On the other hand, bilateral injections of pro-BDNF into the hippocampal dentate gyrus significantly enhanced kindling in wild-type mice but not MMP-9 (Ϫ/Ϫ) mice. These findings suggest that MMP-9 is involved in the progression of behavioral phenotypes in kindled mice because of conversion of pro-BDNF to mature BDNF in the hippocampus.

Increased Expression of Matrix Metalloproteinase-9 in Patients with Temporal Lobe Epilepsy

“…In parallel to these findings Mizoguchi et al provided additional data suggesting that mossy fiber sprouting induced by repeated PTZ treatment was reduced in MMP-9 null mice compared to wild type mice, suggesting that increased hippocampal MMP-9 activity is associated with sprouting of mossy fibers (23). Besides, the previous studies have also revealed that several MMPs are acutely upregulated after status epilepticus (12).…”

“…There are convincing preclinical studies demonstrating that the expression and activity of MMP-9 is regulated by repetitive activation of NMDA receptors (23). In fact, the inhibition of NMDA receptors prevented PTZ-induced convulsions and kindling (9).…”

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

“…Gel zymography was performed to evaluate the activities of MMP-2 and MMP-9. Sample preparation was done as previously described by Mizoguchi et al (34). Samples were run on SDS-PAGE (10%) gels that contained 0.1% gelatin under non-reducing conditions.…”

Role of GPR40 for Fish Oil PUFA-mediated BDNF Synthesis in the Monkey Hippocampus

“…Since the present data showed that increases of m-BDNF and furin concomitant with a decrease of p-BDNF occurred in both the normal and post-ischemic DG tissues in response to the two agonists, it is probable that GPR40 activation stimulated furin to cleave p-BDNF to m-BDNF intracellularly. Likewise, p-BDNF might be secreted extracellularly and might be cleaved by metalloproteinases and/ or plasmin to m-BDNF [11,33]. Among four possible proteolytic enzymes that can be involved in p-BDNF cleavage including furin, proconvertases, metalloproteinases and plasmin, the strongest candidate that can be activated by PUFA-GPR40 signaling may be furin.…”