Neural Regeneration Research (Jan 2024)

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

  • Irene Navarro-Lobato,
  • Mariam Masmudi-Martín,
  • Manuel F López-Aranda,
  • Juan F López-Téllez,
  • Gloria Delgado,
  • Pablo Granados-Durán,
  • Celia Gaona-Romero,
  • Marta Carretero-Rey,
  • Sinforiano Posadas,
  • María E Quiros-Ortega,
  • Zafar U Khan

DOI
https://doi.org/10.4103/1673-5374.389301
Journal volume & issue
Vol. 19, no. 8
pp. 1835 – 1841

Abstract

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Memory deficit, which is often associated with aging and many psychiatric, neurological, and neurodegenerative diseases, has been a challenging issue for treatment. Up till now, all potential drug candidates have failed to produce satisfactory effects. Therefore, in the search for a solution, we found that a treatment with the gene corresponding to the RGS14414 protein in visual area V2, a brain area connected with brain circuits of the ventral stream and the medial temporal lobe, which is crucial for object recognition memory (ORM), can induce enhancement of ORM. In this study, we demonstrated that the same treatment with RGS14414 in visual area V2, which is relatively unaffected in neurodegenerative diseases such as Alzheimer's disease, produced long-lasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer's disease. Furthermore, we found that the prevention of memory deficits was mediated through the upregulation of neuronal arborization and spine density, as well as an increase in brain-derived neurotrophic factor (BDNF). A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer's disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits. These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer's disease. Therefore, our findings of RGS14414 gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

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