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Altered Hippocampal Activation in Seizure-Prone CACNA2D2 Knock-out Mice
Alyssa B Danis1,2, Ashlynn A Gallagher1,2, Ashley N Anderson1,2
1Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, Oregon 97239.
Eneuro
|May 15, 2024
Summary
Mice lacking the α2δ-2 calcium channel subunit show altered hippocampal activity after seizures, with different gene expression patterns but no typical temporal lobe epilepsy pathology. This suggests functional network changes, not structural ones, contribute to epilepsy in these mice.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The voltage-gated calcium channel subunit α2δ-2 (encoded by CACNA2D2) is crucial for calcium signaling in neurons.
- Loss of α2δ-2 function is linked to epilepsy in both mice and humans.
- Understanding hippocampal changes in α2δ-2 deficient mice is key to epilepsy research.
Purpose of the Study:
- To investigate hippocampal activation and histopathological changes in α2δ-2 knock-out (KO) mice.
- To compare c-fos and ΔFosB expression, as well as TLE markers, between wild-type (WT) and KO mice.
Main Methods:
- Immunohistochemical staining and confocal microscopy were used on hippocampal tissue from WT and CACNA2D2 KO mice.
- Expression of activity-dependent genes (c-fos, ΔFosB) was measured.
- Histopathological markers of temporal lobe epilepsy (TLE), including neurogenesis, glial activation, and mossy fiber sprouting, were assessed.
Main Results:
- Baseline c-fos and ΔFosB expression in the dentate granule cell layer (GCL) was similar between WT and KO mice.
- After handling-induced convulsions, KO mice showed reduced c-fos but increased ΔFosB in the dentate gyrus compared to WT.
- KO mice exhibited increased c-fos expression after a subthreshold pentylenetetrazol (PTZ) dose, unlike WT mice.
- Histopathological markers for TLE were largely similar, with a minor increase in hilar mossy cell density in KO mice, contrary to typical TLE findings.
Conclusions:
- Absence of α2δ-2 protein leads to altered seizure-associated dentate gyrus function.
- These functional differences appear to stem from altered network properties rather than structural hippocampal changes.
- The findings suggest a novel mechanism contributing to epilepsy in the absence of α2δ-2.
