Authors :
Maggie Sheridan, BS – Cincinnati Childrens Hosp Medical Center
Mckenzie Rice, PhD – Cincinnati Childrens Hosp Medical Center
Ramona Mahadeshwar, BS – Cincinnati Childrens Hosp Medical Center
Chitra Sunil, BS – Cincinnati Childrens Hosp Medical Center
Christina Gross, PhD – Cincinnati Childrens Hosp Medical Center
Presenting Author: Durgesh Tiwari, PhD – Cincinnati Childrens Hosp Medical Center
Rationale:
Contactin-associated protein-like 2 (CNTNAP2) is a transmembrane protein that mediates neuron glia interaction and regulates dendritic spine growth and neuronal migration. Mutations in the Cntnap2 gene are linked to autism and epilepsy. Younger Cntnap2 KO mice mimic autism phenotypes, while older mice are a model for epilepsy. Thus, comparing behavioral phenotypes across different ages is needed to better understand the age dependent development of disordered brain networks caused due to lack of Cntnap2 expression.
Methods:
Male and female Cntnap2 KO and WT controls were tested across different age groups (4, 5, 7, 9, and ~11 months) using digging, stimulus (reactivity), and nesting assays. Later, mouse brains were perfused and collected for histological analyses using immunohistochemistry.
Results:
Older Cntnap2 KO mice (7, 9, and ~11 months) showed a significant increase in home cage reactivity (stimulus) assay compared to younger mice at 4 and 5 months of age (p< 0.05). Similar trends were observed in male and female Cntnap2 KO mice. No significant differences were observed in the WT controls. A significant difference in digging assay was observed in KO female mice between younger (4 month) and older mice post nest removal (p=0.03). An age-dependent significant reduction in nesting behavior was observed in female KO mice (p=0.006), however no difference was observed in the WT controls.
Conclusions:
Our findings suggest disruption in home cage behavior and reactivity in older epileptic Cntnap2 KO mice indicating an age-dependent network alteration and behavior deficits. Ongoing analysis is looking at the age dependent interneuronal network in the Cntnap2 KO mice using parvalbumin immunostaining.
Funding:
This research was supported by a postdoctoral fellowship from the American Epilepsy Society (D.T), CCTST-MTRS (D.T), and NIH grant R01NS092705 (C.G.), R01NS107453 (C.G).