Dendritic spine head diameter is reduced in the prefrontal cortex of progranulin haploinsufficient mice.
Mol Brain
; 17(1): 33, 2024 Jun 05.
Article
in En
| MEDLINE
| ID: mdl-38840181
ABSTRACT
Loss-of-function mutations in the progranulin (GRN) gene are an autosomal dominant cause of Frontotemporal Dementia (FTD). These mutations typically result in haploinsufficiency of the progranulin protein. Grn+/- mice provide a model for progranulin haploinsufficiency and develop FTD-like behavioral abnormalities by 9-10 months of age. In previous work, we demonstrated that Grn+/- mice develop a low dominance phenotype in the tube test that is associated with reduced dendritic arborization of layer II/III pyramidal neurons in the prelimbic region of the medial prefrontal cortex (mPFC), a region key for social dominance behavior in the tube test assay. In this study, we investigated whether progranulin haploinsufficiency induced changes in dendritic spine density and morphology. Individual layer II/III pyramidal neurons in the prelimbic mPFC of 9-10 month old wild-type or Grn+/- mice were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D reconstruction for morphometry analysis. Dendritic spine density in Grn+/- mice was comparable to wild-type littermates, but the apical dendrites in Grn+/- mice had a shift in the proportion of spine types, with fewer stubby spines and more thin spines. Additionally, apical dendrites of Grn+/- mice had longer spines and smaller thin spine head diameter in comparison to wild-type littermates. These changes in spine morphology may contribute to altered circuit-level activity and social dominance deficits in Grn+/- mice.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prefrontal Cortex
/
Dendritic Spines
/
Haploinsufficiency
/
Progranulins
Limits:
Animals
Language:
En
Journal:
Mol Brain
Journal subject:
BIOLOGIA MOLECULAR
/
CEREBRO
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos