Plasminogen activator is a mitogen for astrocytes in developing cerebellum

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Plasminogen activators (PAs) are enzymes involved in extracellular matrix remodeling.
• Neuronal signaling pathways during development are complex and not fully understood.
• Glial cells play crucial roles in supporting neuronal function and development.

Purpose of the Study:

• To investigate the presence and function of plasminogen activators (PAs) in the developing rat cerebellum.
• To determine if PAs secreted by cerebellar microexplants influence glial cell proliferation and outgrowth.
• To identify the specific types of PAs involved and their potential role as neuronoglial signaling molecules.

Main Methods:

• Culturing newborn rat cerebellum microexplants in Minimal Essential Medium.
• Detecting plasminogen activator (PA) activity using a substrate overlay assay in living cultures.
• Analyzing PA activity via gel electrophoresis and zymography.
• Identifying PA types using specific antisera (urokinase and tissue-type PA).
• Assessing the effect of conditioned medium and purified urokinase on glial cell proliferation.
• Evaluating the impact of the serine protease inhibitor phenyl methanesulfonylfluoride.

Main Results:

• Plasminogen activator (PA) activity was detected in cultured newborn rat cerebellum microexplants.
• Two distinct PA bands (48,000 and 75,000 daltons) were identified as urokinase and tissue-type PA, respectively.
• Cerebellum conditioned medium and purified human urokinase promoted the proliferation and outgrowth of glial fibrillary acid protein-positive cells.
• The mitogenic effect on glial cells was inhibited by phenyl methanesulfonylfluoride.
• PAs are likely of neuronal origin.

Conclusions:

• Newborn rat cerebellar neurons release both urokinase and tissue-type plasminogen activators (PAs).
• These PAs act as mitogenic signals, stimulating the proliferation and outgrowth of glial cells.
• The findings suggest a novel role for PAs in neuronoglial communication during cerebellar development.