Biologic that disrupts PDE11A4 homodimerization in hippocampus CA1 reverses age-related cognitive decline of social memories in mice.

ABSTRACT: Age-related abnormalities in phosphodiesterase 11A (PDE11A), which degrades 3',5'-cAMP/cGMP and is enriched in the ventral hippocampus (VHIPP), drive age-related cognitive decline (ARCD) of social memories. Age-related PDE11A4 ectopically accumulates within the membrane compartment and in filamentous structures termed ghost axons. Previous studies show that expressing an isolated PDE11A4-GAF-B binding domain disrupts homodimerization and reverses aging-like PDE11A4 accumulations in vitro. Here, we show that in vivo lentiviral expression of the isolated PDE11A4-GAFB domain in hippocampal CA1 of aged mice reverses age-related PDE11A4 accumulations and ARCD of social transmission of food preference memory (STFP). It also improves 7-day remote long-term memory for social odor recognition witho

SUBMITTER: Pilarzyk K 

PROVIDER: S-EPMC10528525 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature