RT Journal Article
T1 Microglial angiotensin type 2 receptors mediate sex-specific expression of inflammatory cytokines independently of circulating estrogen
A1 Garrido Gil, Pablo
A1 Pedrosa Sánchez, María Ángeles
A1 García Garrote, María
A1 Pequeño Valtierra, Ana
A1 Rodríguez Castro, Jorge
A1 García Souto, Daniel
A1 Rodríguez Pérez, Ana Isabel
A1 Labandeira García, José Luis
K1 AT2 receptor
K1 Gender
K1 Gonadal hormones
K1 Interleukins
K1 Neuroinflammation
K1 Sex dimorphism
K1 Sex chromosome complement
AB There are sex differences in microglia, which can maintain sex-related gene expression and functional differences in the absence of circulating sex steroids. The angiotensin type 2 (AT2) receptors mediate anti-inflammatory actions in different tissues, including brain. In mice, we performed RT-PCR analysis of microglia isolated from adult brains and RNA scope in situ hybridization from males, females, ovariectomized females, orchiectomized males and brain masculinized females. We also compared wild type and AT2 knockout mice. The expression of AT2 receptors in microglial cells showed sex differences with much higher AT2 mRNA expression in females than in males, and this was not dependent on circulating gonadal hormones, as observed using ovariectomized females, brain masculinized females and orchiectomized males. These results suggest genomic reasons, possibly related to sex chromosome complement, for sex differences in AT2 expression in microglia, as the AT2 receptor gene is located in the X chromosome. Furthermore, sex differences in expression of AT2 receptors were associated to sex differences in microglial expression of key anti-inflammatory cytokines such as interleukin-10 and pro-inflammatory cytokines such as interleukin-1β and interleukin-6. In conclusion, sex differences in microglial AT2 receptor expression appear as a major factor contributing to sex differences in the neuroinflammatory responses beyond the effects of circulating steroids
PB Wiley
SN 0894-1491
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29720
UL http://hdl.handle.net/10347/29720
LA eng
NO Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, Grant/Award Numbers: XUGA, ED431C 2018/10, ED431G/05; Instituto de Salud Carlos III, Grant/Award Numbers: PI20/00385, RD16/0011/0016, CIBERNED; Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: RTI2018-098830-B-I00; Regional European Development Fund (FEDER)
NO There are sex differences in microglia, which can maintain sex-related gene expression and functional differences in the absence of circulating sex steroids. The angiotensin type 2 (AT2) receptors mediate anti-inflammatory actions in different tissues, including brain. In mice, we performed RT-PCR analysis of microglia isolated from adult brains and RNA scope in situ hybridization from males, females, ovariectomized females, orchiectomized males and brain masculinized females. We also compared wild type and AT2 knockout mice. The expression of AT2 receptors in microglial cells showed sex differences with much higher AT2 mRNA expression in females than in males, and this was not dependent on circulating gonadal hormones, as observed using ovariectomized females, brain masculinized females and orchiectomized males. These results suggest genomic reasons, possibly related to sex chromosome complement, for sex differences in AT2 expression in microglia, as the AT2 receptor gene is located in the X chromosome. Furthermore, sex differences in expression of AT2 receptors were associated to sex differences in microglial expression of key anti-inflammatory cytokines such as interleukin-10 and pro-inflammatory cytokines such as interleukin-1β and interleukin-6. In conclusion, sex differences in microglial AT2 receptor expression appear as a major factor contributing to sex differences in the neuroinflammatory responses beyond the effects of circulating steroids
DS Minerva
RD 28 abr 2026