PRDX6 inhibits neurogenesis of neural precursor cells through downregulation of wdfy1 mediated TLR4 signal

Abstract

Impaired neurogenesis has been associated with brain disorders. The role of peroxiredoxin 6 (PRDX6) in the neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared neurogenesis ability and studied the molecular mechanisms. It was found that the neurogenesis of neural stem cells and expression of the marker protein were lowered in PRDX6 Tg-mice compared with non-tg mice. Moreover, the expression of wdfy1 was dramatically decreased in PRDX6-Tg mice, also, we observed that wdfy1 siRNA decreases the differentiation ability of primary neural stem cells to astrocyte and neuronal cells as well as PC12 cells. However, knockdown of PRDX6 recovered neurogenesis in the brain of PRDX6-Tg mice as well as PC-12 cells. We also showed that TLR4 was dramatically reduced in PRDX6 Tg mice as well as PC-12 cells and PRDX6 overexpression reduced neurogenesis was rescued after treatment of TLR4 siRNA.We further found that reduced TLR4 expression and neurogenesis was reversed in the neuron from PRDX6-Tg mice as well as PC12 cells by introduction of wdfy1 plasmid. Moreover, TLR4 siRNA reduced neurogenesis and wdfy1 expression. This study indicated that PRDX6 inhibits neurogenesis of neural precursor cells through TLR4 dependent downregulation of wdfy1.

Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes

“…As expected, we observed a decrease in Nrcam expression in KO compared to wild-type control mice in each tanycyte subset ( Figure 6C ) and a decrease in Nestin and Rax ( Figure 6C ), adding weight to the idea that tanycytes are reduced in the NrCAM KO mouse. We also observed reduced levels of Hes1 and Prdx6— both previously implicated in regulating the balance of radial glial-like neural stem cells and neurons elsewhere in the CNS ( Bai et al, 2007 ; Park et al, 2016 ; Bosze et al, 2020 ) and reduced levels of Metr , a gene implicated in astrocyte differentiation ( Nishino et al, 2004 ; Supplementary Table 1 ). Additionally, we observed lower levels of the tanycyte-enriched genes, Ndn , Crym and Gpr50 , previously shown to regulate thyroid hormone signaling ( Figure 6C and Supplementary Table 1 ; Bechtold et al, 2012 ; Hasegawa et al, 2012 ; Kinney and Bloch, 2021 ).…”

The neural cell adhesion molecule NrCAM regulates development of hypothalamic tanycytes

“…As expected, we observed a decrease in NrCAM in KO compared to wildtype control mice in each tanycyte subset (Fig 6C ) and a decrease in Nestin and Rax (Fig 6C), adding weight to the idea that tanycytes are reduced in the NrCAM KO mouse. We also observed reduced levels of Hes1 and Prdx6 -both previously implicated in regulating the balance of radial glial-like neural stem cells and neurons elsewhere in the CNS (Park et al;Bai et al, 2007;Bosze et al, 2020) and reduced levels of metr, a gene implicated in astrocyte differentiation (Nishino et al, 2004) (Table 1). Finally, we observed lower levels of the tanycyte-enriched genes, Ndn, Crym and Gpr50, previously shown to regulate thyroid hormone signaling (Fig 6C ; Table 1) (Bechtold et al, 2012;Hasegawa et al, 2012;Kinney and Bloch, 2021).…”