Abstract
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.
Highlights
Transthyretin (TTR) is a 55 kDa homotetrameric protein, composed of four identical subunits, each containing 127 amino acids [1]
TTR is mainly synthesized by the liver and by the epithelial cells of the choroid plexus (CP), which are the sources of TTR in plasma and cerebrospinal fluid (CSF), respectively [2,3]
The present study was conducted to evaluate if transthyretin (TTR), a major transport protein for thyroid hormones and retinol-binding protein in the plasma and CSF, is expressed in the postischemic brain during the first 14 days following permanent focal ischemia induced by photothrombosis (PT)
Summary
Transthyretin (TTR) is a 55 kDa homotetrameric protein, composed of four identical subunits, each containing 127 amino acids [1]. TTR is mainly synthesized by the liver and by the epithelial cells of the choroid plexus (CP), which are the sources of TTR in plasma and cerebrospinal fluid (CSF), respectively [2,3]. TTR is one of the most abundant proteins in the CSF (up to 25% of total CSF protein) and, of both humans and rodents, it is the carrier protein of 3,5,3’,5’tetraiodo-L-thyronine (T4) and 3,5,3’-triodo-L-thyronine (T3), TTR has much higher affinity for T4 than T3. Swedish Brain Fund (No FO2019-0254 and FO2018-0316) (KR), ALF Skåne (KR), Sparbanksstiftelsen Fars & Frosta (KR), the Crafoord Foundation (KR), Sveriges Stroke Riksforbundet (KR), the Hans-Christian and Alice Wachtmeister Foundation (KR) and the Stiftelsen Sven-Olof Jansons livsverk (KR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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