Related Experiment Video
Updated: Sep 15, 2025
Using a Bipolar Electrode to Create a Temporal Lobe Epilepsy Mouse Model by Electrical Kindling of the Amygdala
Published on: June 29, 2022
Comorbidities in the mouse model of temporal lobe epilepsy induced by intrahippocampal kainate
Loan Samalens1,2, Camille Beets1, Clothilde Courivaud1
1Grenoble Institut Neurosciences, Université Grenoble Alpes, Inserm, U1216, Grenoble, France.
Objective:
Mesial temporal lobe epilepsy (MTLE) is generally associated with cognitive and psychiatric comorbidities. Here we examined whether similar comorbidities are observed in mice injected with kainate in the dorsal hippocampus, a model known to recapitulate many features of human MTLE, and if these comorbidities are sex dependent.
Methods:
Male and female C57BL/6 mice were unilaterally injected with kainate in the dorsal hippocampus (KA-MTLE), and hippocampal paroxysmal discharges were recorded over 2 months. Behavioral tests assessed food intake (Novelty Palatable Food Intake test), well-being (Nesting), impulsivity (Marbles test), depression-related behavior (Splash test), spatial learning and memory (Barnes maze), working memory (Y-maze), motor coordination (Climbing Cage test), locomotion and activity (Open Field), and anxiety-like behavior (Elevated Plus Maze). Body weight and estrous cycle were also monitored and compared to saline-injected mice (sham).
Results:
We observed reduced environmental care (Nesting) but no changes in self-care (Splash test) or impulsivity (Marbles test) in KA-MTLE mice. Spatial memory (Barnes maze) was unaffected, although less efficient strategies were used by these mice. Working memory (Y-maze) remained similar to that of shams. No motor impairments were observed (Climbing Cage test, Open Field), but KA-MTLE mice displayed increased activity without anxiety-like behavior. They gained more weight, while their palatable food intake did not differ from shams, and females showed longer estrous cycles. Death that might correspond to sudden unexpected death in epilepsy (SUDEP) occurred in 10% and 3% of epileptic male and female mice, respectively, vs 0% in shams.
Significance:
Our results suggest that KA-MTLE mice display several features (hyperactivity, reduced well-being, subtle cognitive changes) evocative of an attention disorder associated with hyperactivity (attention-deficit/hyperactivity disorder [ADHD]), often described in young patients with MTLE. Along with the increase in body weight and the occurrence of SUDEP, our data further validate this mouse model to study the physiopathology of MTLE and develop treatments for both seizures and associated comorbidities.
Insights
Kainate-induced mesial temporal lobe epilepsy (MTLE) mouse models show hyperactivity and reduced well-being, similar to attention-deficit/hyperactivity disorder (ADHD) in human patients. These findings validate the model for studying MTLE comorbidities and potential treatments.
Area of Science:
- Neuroscience
- Epilepsy Research
- Animal Models of Disease
Background:
- Mesial temporal lobe epilepsy (MTLE) is frequently accompanied by cognitive and psychiatric issues.
- The kainate-induced dorsal hippocampus model (KA-MTLE) in mice mimics key aspects of human MTLE.
- Investigating sex-dependent comorbidities in this model is crucial for understanding MTLE.
Purpose of the Study:
- To determine if KA-MTLE mice exhibit comorbidities similar to human MTLE patients.
- To assess if these comorbidities are influenced by sex.
- To validate the KA-MTLE mouse model for studying epilepsy-associated conditions.
Main Methods:
- Male and female C57BL/6 mice received unilateral kainate injections in the dorsal hippocampus.
- Behavioral tests evaluated food intake, well-being, impulsivity, depression, spatial and working memory, motor coordination, locomotion, and anxiety.
- Body weight, estrous cycles, and seizure activity were monitored over two months.
Main Results:
- KA-MTLE mice showed reduced environmental care and increased activity without anxiety or motor deficits.
- Spatial and working memory were largely unaffected, though strategy use differed.
- Increased body weight and longer estrous cycles in females were observed; sudden unexpected death in epilepsy (SUDEP) occurred in 10% of males and 3% of females.
Conclusions:
- KA-MTLE mice exhibit hyperactivity and reduced well-being, mirroring attention-deficit/hyperactivity disorder (ADHD) symptoms seen in human MTLE patients.
- The model recapitulates weight gain and SUDEP, supporting its use for studying MTLE pathophysiology.
- This validated model aids in developing treatments for both seizures and associated comorbidities in MTLE.
