Diminished expression of microtubule-associated protein (MAP-2) and beta-tubulin as a putative marker for ischemic injury in neocortical transplants.
The present study examined the immunoexpression of the neuronal cytoskeletal proteins, MAP-2 and beta-tubulin within a timed series of rat fetal neocortical transplants. beta-tubulin is a major component of microtubules and MAP-2 regulates the assembly and stability of neuronal microtubules and is a major site for the phosphorylation cAMP dependent protein kinase in neurons. Both proteins are strongly expressed in the soma and dendrites of normal neurons. MAP-2 has been shown to be a sensitive marker for ischemia in neurons and is downregulated in this form of injury. Immunoexpression of both MAP-2 and beta-tubulin in grafted cortical neurons was markedly reduced when compared to age-matched or even perinatal specimens at all post-operative times. Dendritic staining was confined to random, thin processes with no laminar patterns and staining within somata was very weak. In some specimens, somatic expression was increased and dendrites were more robustly stained when a portion of the graft was juxtaposed to a fiber tract even though in other regions of the same graft there was very weak immunostaining. The present results corroborate previous studies of cortical transplants indicating an immature structure and metabolism, and it is suggested here that the primary factor is a sublethal form of ischemic injury. Another possibility for the relative paucity of cytoskeletal protein expression could be that transplanted neurons undergo a new developmental scheme (neodevelopment) that is brought about by truncated migration patterns and abnormal synaptic connections.
Rosenstein
J M
JM
Department of Anatomy, George Washington University Medical Center, Washington, DC 20037, USA.
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D016380:Brain Tissue Transplantation; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014404:Tubulin / Q000096:biosynthesis*
D015415:Biomarkers; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D014404:Tubulin