| First Author | Bland KM | Year | 2021 |
| Journal | Neurobiol Dis | Volume | 150 |
| Pages | 105253 | PubMed ID | 33421563 |
| Mgi Jnum | J:307760 | Mgi Id | MGI:6707128 |
| Doi | 10.1016/j.nbd.2021.105253 | Citation | Bland KM, et al. (2021) FMRP regulates the subcellular distribution of cortical dendritic spine density in a non-cell-autonomous manner. Neurobiol Dis 150:105253 |
| abstractText | Fragile X syndrome (FXS) is the most common form of intellectual disability that arises from the dysfunction of a single gene-Fmr1. The main neuroanatomical correlate of FXS is elevated dendritic spine density on cortical pyramidal neurons, which has been modeled in Fmr1(-/Y) mice. However, the cell-autonomous contribution of Fmr1 on cortical dendritic spine density has not been assessed. Even less is known about the role of Fmr1 in heterozygous female mosaic mice, which are a putative model for human Fmr1 full mutation carriers (i.e., are heterozygous for the full Fmr1-silencing mutation). In this neuroanatomical study, spine density in cortical pyramidal neurons of Fmr1(+/-) and Fmr1(-/Y) mice was studied at multiple subcellular compartments, layers, and brain regions. Spine density in Fmr1(+/-) mice is higher than WT but lower than Fmr1(-/Y). Not all subcellular compartments in layer V Fmr1(+/-) and Fmr1(-/Y) cortical pyramidal neurons are equally affected: the apical dendrite, a key subcellular compartment, is principally affected over basal dendrites. Within apical dendrites, spine density is differentially affected across branch orders. Finally, identification of FMRP-positive and FMRP-negative neurons within Fmr1(+/-) permitted the study of the cell-autonomous effect of Fmr1 on spine density. Surprisingly, layer V cortical pyramidal spine density between FMRP-positive and FMRP-negative neurons does not differ, suggesting that the regulation of the primary neuroanatomical defect of FXS-elevated spine density-is non-cell-autonomous. |
