Abstract
Choroid plexus epithelial cells produce and secrete transthyretin (TTR). TTR binds and distributes thyroid hormone (TH) to brain cells via the cerebrospinal fluid. The adult murine subventricular zone (SVZ) is in close proximity to the choroid plexus. In the SVZ, TH determines neural stem cell (NSC) fate towards a neuronal or a glial cell. We investigated whether the loss of TTR also disrupted NSC fate choice. Our results show a decreased neurogenic versus oligodendrogenic balance in the lateroventral SVZ of Ttr knockout mice. This balance was also decreased in the dorsal SVZ, but only in Ttr knockout male mice, concomitant with an increased oligodendrocyte precursor density in the corpus callosum. Quantitative RTqPCR analysis following FACS-dissected SVZs, or marked-coupled microbeads sorting of in vitro neurospheres, showed elevated Ttr mRNA levels in neuronal cells, as compared to uncommitted precursor and glial cells. However, TTR protein was undetectable in vivo using immunostaining, and this despite the presence of Ttr mRNA-expressing SVZ cells. Altogether, our data demonstrate that TTR is an important factor in SVZ neuro- and oligodendrogenesis. They also reveal important gender-specific differences and spatial heterogeneity, providing new avenues for stimulating endogenous repair in neurodegenerative diseases.
Highlights
Choroid plexus epithelial cells produce and secrete transthyretin (TTR)
We assessed whether TTR regulates neuro- and oligodendrogenesis in the subventricular zone (SVZ) of adult mice by analysing consequences for the neuron/glia balance in the absence of TTR
TTR production and secretion by choroid plexus epithelial cells facilitates the distribution of thyroid hormone (TH) via the cerebrospinal fluid (CSF), enabling access to target brain cells[1,3,4]
Summary
Choroid plexus epithelial cells produce and secrete transthyretin (TTR). TTR binds and distributes thyroid hormone (TH) to brain cells via the cerebrospinal fluid. In the central nervous system, TTR is produced by choroid plexus epithelial cells facilitating TH distribution across the blood-cerebrospinal fluid (CSF) barrier, allowing THs to reach various regions within the brain, one of the most TH-sensitive organs[3,4]. The subventricular zone (SVZ), lining the lateral ventricular walls, is a key neurogenic region in close contact with the CSF5 This stem cell niche sustains lifelong de novo generation of neurons and oligodendrocytes[6]. This is relevant to neurodegenerative diseases, which are characterised by neuronal or glial cell loss, and show gender-specific susceptibility. It has been shown that TH is required for efficient remyelination[30,31]
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