| Popis: |
The relationship between hormonal fluctuations and changes to structure and function of CNS are well established during aging. Studies show increased peripheral LH is associated with decreased brain LHR signaling, and loss of cognition and structural plasticity. Additionally, treatments that lower peripheral LH and increase brain LHR signaling or directly activate LHR via ligand administration rescue cognition as well as signaling related to memory and structural plasticity. Interestingly, hormonal fluctuations are not limited to aging and circulating hormones, including LH, change throughout postnatal period into adulthood, which are characterized by massive changes to structure and functional change in CNS. However, the relationship between LH and LHR with CNS development is less described. Here, we determined expression of LH and LHR throughout lifespan and correlated with markers of synaptogenesis and spinogenesis. We found that expression of LH and LHR are region, sex, and age dependent. Additionally, we showed interesting correlations of LHR with synaptic markers suggesting distinct functions at different time-periods. Furthermore, we used CRISPR/Cas9 system to create gene edits in LHR in a CNS-specific manner to address LHR mechanism in CNS. We successfully created gene-edits within LHR in the CNS, however, they were not sufficient for LHR knockout highlighting a potential difficulty in targeting a complex gene such as LHR using CRISPR/Cas9 system. |
