Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy

  1. Fernández-Albarral, José A. 1
  2. Salobrar-García, Elena 11
  3. Matamoros, José A. 11
  4. Fernández-Mendívil, Cristina 3
  5. del Sastre, Eric 23
  6. Chen, Lejing 1
  7. de Hoz, Rosa 11
  8. López-Cuenca, Inés 1
  9. Sánchez-Puebla, Lidia 1
  10. Ramírez, José M. 11
  11. Salazar, Juan J. 11
  12. Lopez, Manuela G. 23
  13. Ramírez, Ana I. 11
  1. 1 Universidad Complutense de Madrid
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    Universidad Complutense de Madrid

    Madrid, España

    ROR 02p0gd045

  2. 2 Universidad Autónoma de Madrid
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    Universidad Autónoma de Madrid

    Madrid, España

    ROR https://ror.org/01cby8j38

  3. 3 Hospital Universitario de la Princesa
    info

    Hospital Universitario de la Princesa

    Madrid, España

    ROR https://ror.org/03cg5md32

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Revista:
Antioxidants

ISSN: 2076-3921

Año de publicación: 2022

Volumen: 11

Número: 11

Páginas: 2151

Tipo: Artículo

DOI: 10.3390/ANTIOX11112151 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Antioxidants

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Resumen

Tauopathies such as Alzheimer’s disease are characterized by the accumulation of neurotoxic aggregates of tau protein. With aging and, especially, in Alzheimer’s patients, the inducible enzyme heme oxygenase 1 (HO-1) progressively increases in microglia, causing iron accumulation, neuroinflammation, and neurodegeneration. The retina is an organ that can be readily accessed and can reflect changes that occur in the brain. In this context, we evaluated how the lack of microglial HO-1, using mice that do not express HO-1 in microglia (HMO-KO), impacts retinal macro and microgliosis of aged subjects (18 months old mice) subjected to tauopathy by intrahippocampal delivery of AAV-hTauP301L (TAU). Our results show that although tauopathy, measured as anti-TAUY9 and anti-AT8 positive immunostaining, was not observed in the retina of WT-TAU or HMO-KO+TAU mice, a morphometric study of retinal microglia and macroglia showed significant retinal changes in the TAU group compared to the WT group, such as: (i) increased number of activated microglia, (ii) retraction of microglial processes, (iii) increased number of CD68+ microglia, and (iv) increased retinal area occupied by GFAP (AROA) and C3 (AROC3). This retinal inflammatory profile was reduced in HMO-KO+TAU mice. Conclusion: Reduction of microglial HO-1 could be beneficial to prevent tauopathy-induced neuroinflammation.

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Información de financiación

This research was funded by the Research Network RETIBRAIN (RED2018-102499-T) of the Spanish Ministry of Science and Innovation, and the Spanish Ministry of Science and Innovation Ref. RTI2018-095793-B-I00 and Ref. PID2021-125986OB-I00. J.A.F.-A. is currently supported by a Predoctoral Fellowship (FPU17/01023) from the Spanish Ministry of Science, Innovation, and Universities. E.d.S. is currently supported by a Predoctoral Fellowship (FPU18/00630) from the Spanish Ministry of Science, Innovation, and Universities. I.L.-C. is currently supported by a Predoctoral Fellowship (CT42/18-CT43/18) from the Complutense University of Madrid. L.S.-P. is currently supported by a Predoctoral Fellowship (CT82/20-CT83/20) from the Complutense University of Madrid. The sponsor or funding organization had no role in the design or conduct of this research.

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