The potential role of metalloproteinases in neurogenesis in the gerbil hippocampus following global forebrain ischemia

• Published in: PloS one 2011-07, Vol.6 (7), p.e22465
• Main Authors: Wójcik-Stanaszek, Luiza, Sypecka, Joanna, Szymczak, Patrycja, Ziemka-Nalecz, Malgorzata, Khrestchatisky, Michel, Rivera, Santiago, Zalewska, Teresa
• Format: Article
• Language: English
• Subjects: Activation; Angiogenesis; Animals; Biology; Brain; Brain injury; Brain Ischemia - enzymology; Brain Ischemia - pathology; Brain research; Cell adhesion & migration; Cell Hypoxia - drug effects; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Cells (biology); Cord blood; Dentate gyrus; Differentiation; DNA repair; Extracellular matrix; Extracellular Space - drug effects; Extracellular Space - enzymology; Forebrain; Gerbillinae; Growth factors; Hippocampus; Hippocampus - drug effects; Hippocampus - enzymology; Hippocampus - pathology; Humans; Immunoglobulins; Ischemia; Localization; Male; Matrix metalloproteinases; Medical research; Medicine; Metalloproteases - antagonists & inhibitors; Metalloproteases - metabolism; Morphology; Nervous system; Neural stem cells; Neurogenesis; Neurogenesis - drug effects; Neurons; Neurons - drug effects; Neurons - enzymology; Neurons - pathology; Prosencephalon; Protease Inhibitors - pharmacology; Proteases; Pyramidal cells; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; Rodents; Stem cells; Stem Cells - drug effects; Stem Cells - enzymology; Stem Cells - pathology; Umbilical cord
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022465

Matrix metalloproteinases (MMPs) have recently been considered to be involved in the neurogenic response of adult neural stem/progenitor cells. However, there is a lack of information showing direct association between the activation of MMPs and the development of neuronal progenitor cells involving proliferation and/or further differentiation in vulnerable (Cornus Ammoni-CA1) and resistant (dentate gyrus-DG) to ischemic injury areas of the brain hippocampus. We showed that dynamics of MMPs activation in the dentate gyrus correlated closely with the rate of proliferation and differentiation of progenitor cells into mature neurons. In contrast, in the damaged CA1 pyramidal cells layer, despite the fact that some proliferating cells exhibited antigen specific characteristic of newborn neuronal cells, these did not attain maturity. This coincides with the low, near control-level, activity of MMPs. The above results are supported by our in vitro study showing that MMP inhibitors interfered with both the proliferation and differentiation of the human neural stem cell line derived from umbilical cord blood (HUCB-NSCs) toward the neuronal lineage. Taken together, the spatial and temporal profiles of MMPs activity suggest that these proteinases could be an important component in neurogenesis-associated processes in post-ischemic brain hippocampus.