The dual response of protein kinase Fyn to neural trauma: early induction in neurons and delayed induction in reactive astrocytes.

Abstract

In the developing central nervous system, a src-related protein-tyrosine kinase fyn participates in the myelination process, neuronal growth, and cytoskeletal organization. In adults, fyn has been implicated in learning and memory formation. To test if fyn expression is modulated by neuronal activity, we performed quantitative in situ hybridization (ISH) using brain sections of the adult rats that had undergone either kainic acid (KA)-induced seizures or neuronal deafferentation (entorhinal cortex lesion, ECL). In the KA model, a few hours after seizure activities, fyn mRNA was elevated in the dentate gyrus (DG) (+45%), cerebral cortex layer III (+35%), and piriform cortex (+25%). Conversely, fyn mRNA consistently decreased in the hippocampal neurons after transection of the major axonal inputs from the entorhinal cortex. Although fyn expression in the brain has been allegedly limited to neurons and oligodendrocytes, we provide in this study the first evidence that fyn mRNA is highly expressed in the astrocytes involved in reactive gliosis. In the KA model, the occurrence of fyn-overexpressing astrocytes increased with the progress of neuronal damage in the CA1 and CA3 regions of the hippocampus. In contrast, fyn-overexpressing astrocytes were not observed in the granular cell layer of dentate gyrus (DG), where neurons were not damaged. Likewise, in the ECL model, the most drastic change in fyn mRNA expression took place at the reactive astrocytes near the stab wound sites, where fyn mRNA levels were doubled 4-10 d after the lesion. Collectively, our data suggest that (i) an early induction of fyn mRNA in neurons is linked to neuronal activity, and (ii) the delayed induction of fyn mRNA in reactive astrocytes near the damaged cells may play novel signaling roles during glial response.

• Authors: Jong T Chun, Marianna Crispino, Georges Tocco
• Journal: Experimental neurology (Exp Neurol) Vol. 185 Issue 1 Pg. 109-19 (Jan 2004) ISSN: 0014-4886 [Print] United States
• PMID: 14697322 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proto-Oncogene Proteins
• RNA Probes
• RNA, Messenger
• Fyn protein, mouse
• Fyn protein, rat
• Proto-Oncogene Proteins c-fyn
• Kainic Acid

Topics

• Animals
• Astrocytes (enzymology, pathology)
• Blotting, Western
• Brain Damage, Chronic (enzymology, pathology, physiopathology)
• Cell Death
• Cells, Cultured
• Disease Models, Animal
• Entorhinal Cortex (pathology, physiopathology)
• Enzyme Induction
• Kainic Acid
• Male
• Mice
• Neurons (enzymology, pathology)
• Organ Specificity
• Perforant Pathway (physiopathology, surgery)
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins c-fyn
• RNA Probes (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Seizures (chemically induced, enzymology, pathology)