Integrins are involved in synaptogenesis, cell spreading, and adhesion in the postnatal brain.
Integrins are a major family of heterodimeric surface glycoproteins that act as adhesion molecules, have a spectrum of extracellular matrix (ECM) molecules as their ligands, and regulate a variety of cellular functions. Integrins are known to be critical to embryonic brain development, and recent studies have indicated their essential role in adult brain function, although their role in postnatal brain development and function has not been examined. Here, we used the organotypic slice culture system to investigate the role of integrins in postnatal hippocampal development by exposing the tissue to either an integrin competitive antagonist, the peptide GRGDSP containing Arg-Gly-Asp (RGD) attachment site, or to function-blocking beta(1)-integrin antibodies to disrupt integrin interactions. These experiments revealed that beta(1)-integrin antibodies interfered with spreading of the culture, resulting in a rapid and marked diminution of slice area. beta(1)-integrin antibodies and RGD peptide disrupted cell adhesion, causing cell detachment and migration of glial cells from the explant. The majority of the detached cells were of macroglial origin and switched to expression of the intermediate filament proteins vimentin and nestin, suggesting a developmental regression. The organotypic organization of slice cultures was not affected, although exposure to either integrin antagonist or antibody resulted in a statistically significant reduction in the number of synapses measured in the apical dendrites of CA1 pyramidal neurons. The results demonstrate that integrins markedly affect postnatal CNS development, in both ultrastructural construction and organizational processes.
Nikonenko
Irina
I
Department of Pharmacology, Centre Médical Universitaire, 1211 4, Geneva, Switzerland. inikon@hotmail.com
Toni
Nicolas
N
Moosmayer
Marlis
M
Shigeri
Yasushi
Y
Muller
Dominique
D
Sargent Jones
Leslie
L
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D000906:Antibodies; D019012:Integrin beta1; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline