Transthyretin expression in the postischemic brain

• Published in: PloS one Vol. 14; no. 9; p. e0221555
• Main Authors: Talhada, Daniela, Gonçalves, Isabel, Gomes, João Carlos, Saraiva, Maria João, Reis Santos, Cecília, Ruscher, Karsten
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.09.2019; Public Library of Science (PLoS)
• Subjects: Alzheimer's disease; Animals; Astrocytes; Astrocytes - metabolism; Basic Medicine; Biology and Life Sciences; Brain; Brain - metabolism; Brain - pathology; Brain Ischemia - genetics; Brain Ischemia - metabolism; Brain Ischemia - pathology; Brain research; Bupivacaine; Cerebrospinal fluid; Choroid plexus; Choroid Plexus - metabolism; Choroid Plexus - pathology; Disease Models, Animal; Gene Expression; Glial fibrillary acidic protein; Globules; Health sciences; Immunoblotting; Immunohistochemistry; Ischemia; Laboratories; Legumain; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine and Health Sciences; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Microglia; Microglia - metabolism; Neurodegeneration; Neuronal-glial interactions; Neurons; Neurons - metabolism; Neurosciences; Neurosurgery; Neurovetenskaper; Peptides; Polymerase chain reaction; Prealbumin - cerebrospinal fluid; Prealbumin - genetics; Prealbumin - metabolism; Proteins; Recovery of function; Research and Analysis Methods; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stroke; Studies; Synthesis; Territory; Transthyretin; Transthyretin amyloidosis; United States > US; Portugal; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221555

The unknown role of the carrier protein transthyretin (TTR) in mechanisms of functional recovery in the postischemic brain prompted us to study its expression following experimental stroke. Male C57/B6 mice (age 9 to 10 weeks) were subjected to permanent focal ischemia induced by photothrombosis (PT) and brain tissues were analyzed for ttr expression and TTR levels at 24 hours, 48 hours, 7 days and 14 days following the insult by RT-PCR, Western blot and immunohistochemistry. Fourteen days after PT, non-specific TTR-like immunoreactive globules were found in the ischemic core and surrounding peri-infarct region by immunohistochemistry that could not be allocated to DAPI positive cells. No TTR immunoreactivity was found when stainings were performed with markers for neurons (Neuronal Nuclei, NeuN), reactive astrocytes (glial fibrillary acidic protein, GFAP) or microglia (cluster of differentiation 68, CD68). In addition, we could not find TTR by immunoblotting in protein extracts obtained from the ischemic territory nor ttr expression by RT-PCR at all time points following PT. In all experiments, ttr expression in the choroid plexus and TTR in the mouse serum served as positive controls and recombinant legumain peptide as negative control. Together, our results indicate that TTR is not synthesized in brain resident cells in the ischemic infarct core and adjacent peri-infarct area. Thus, it seems unlikely that in situ synthesized TTR is involved in mechanisms of tissue reorganization during the first 14 days following PT.