title: Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia.
abstract: Although transforming growth factor-beta (TGF-beta) is known to be multifunctional in many physiological systems, its role in the brain is undergoing elucidation. The situation is made more complex by the presence of multiple isoforms, which may be differentially regulated and have various activities in each particular cell type. Because neurons are dependent on neurotrophic factors for survival, we utilized a rat model of transient forebrain ischemia (TFI) to test the hypothesis that TGF-beta isoforms are important in the hippocampal response to injury. Northern blot analysis demonstrated a differential and temporal alteration in TGF-beta isoform expression following TFI. In-situ hybridization experiments revealed that at day 1 following TFI, there was a strong neuronal increase in the TGF beta-1 transcript but a reciprocal decrease in TGF-beta 2 and -beta 3 transcript levels. Immunohistochemical analysis of all three TGF-beta s demonstrated at day 1 following TFI a loss of the immunoreactive proteins in the vulnerable CA-1 hippocampal neurons, but protein preservation in the CA-2-4 neurons which are more resistant to the ischemic insult. At 3-5 days following TFI, significant extraneuronal changes in TGF-beta isoform expression were also detected. Double-staining experiments with antibody to glial fibrillary acidic protein (GFAP) as a marker for astrocytes, and lectin isolectin B4 Griffonia simplicifolia for microglia, demonstrated increased expression of all TGF-beta isoforms in astrocytes but not microglia. Taken together, these results suggest that the TGF-beta peptides in neurons and astrocytes are important endogenous mediators in the CNS response to ischemic injury.
authors.affiliation: Department of Neurosurgery, Sir Charles Gairdner Hospital, Perth, W.A., Australia.
authors.forename: N W
authors.initials: NW
authors.lastname: Knuckey
authors.forename: P
authors.initials: P
authors.lastname: Finch
authors.forename: D E
authors.initials: DE
authors.lastname: Palm
authors.forename: M J
authors.initials: MJ
authors.lastname: Primiano
authors.forename: C E
authors.initials: CE
authors.lastname: Johanson
authors.forename: K C
authors.initials: KC
authors.lastname: Flanders
authors.forename: N L
authors.initials: NL
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D016212:Transforming Growth Factor beta