Epidermal growth factor-induced cell proliferation in the adult rat striatum

• Published in: Brain research Vol. 1007; no. 1; pp. 29 - 38
• Main Authors: McGinn, Melissa J., Sun, Dong, Schneider, Stacie L., Alexander, John K., Colello, Raymond J.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 08-05-2004; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Autoradiography - methods; Biological and medical sciences; Bromodeoxyuridine - metabolism; Cell Count - methods; Cell Division - drug effects; Cell physiology; CNS; Corpus Striatum - cytology; Dose-Response Relationship, Drug; Drug Administration Schedule; Ectodysplasins; Epidermal Growth Factor - administration & dosage; Epidermal Growth Factor - pharmacology; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; Gliogenesis; Growth factors; Humans; Immunohistochemistry - methods; Intermediate Filament Proteins - metabolism; Male; Membrane Proteins - metabolism; Mitogens; Molecular and cellular biology; Nerve Tissue Proteins - metabolism; Nestin; Neurogenesis; Neuroglia - metabolism; Neurons - cytology; Neurons - drug effects; Phosphopyruvate Hydratase - metabolism; Rats; Rats, Wistar; Responses to growth factors, tumor promotors, other factors; Staining and Labeling - methods; Stem cells; Thymidine - pharmacokinetics; Tritium - pharmacokinetics; Vimentin - metabolism; Development and regeneration; Stem cells; CNS; Gliogenesis; Growth factors; Mitogens; Neurogenesis; Cell proliferation; Glial cell; Rat; Neuroglia; Stem cell; Rodentia; Central nervous system; Basal ganglion; Corpus striatum; Encephalon; Vertebrata; Mammalia; Epidermal growth factor; Neuron; Mitogen
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2003.12.054

Current strategies for repairing the adult CNS following injury include cell transplantation and/or the use of viral vectors to deliver therapeutic agents. Although promising, both techniques are limited in their usefulness due to the immunological response triggered in the brain as a result of the introduction of foreign antigens. An alternative method to repair the damaged CNS is to stimulate endogenous cells within the brain to divide thereby replacing cells lost to injury. Since it has been shown that growth factors such as epidermal growth factor (EGF) are potent mitogens to CNS cells in vitro, we sought to assess the mitogenic effect of an in vivo application of EGF to the adult mammalian brain. Accordingly, varying doses of human recombinant EGF were administered to the striatum of adult rats, followed 48 h later by intraperitoneal injections of 5-bromodeoxyuridine (BrdU), a marker for cell proliferation. Of four doses assessed, 0.05 ng of EGF induced the highest levels of cell proliferation. To determine the cellular identity of these proliferating cells, animals were injected with
3H-thymidine 48 h following EGF administration to label dividing cells. Sections were subsequently immunostained for markers to astrocytes, microglia, oligodendrocytes, neural precursors, and mature neurons. Compared to controls, a significant proportion of the newly generated cells resulting from EGF administration were identified as immature and mature astrocytes. Collectively, these results provide valuable information for utilizing a growth factor administration approach to mobilize the proliferative response of endogenous cells to replace those lost to injury or disease.