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Neuron subset-specific Pten deletion induces abnormal skeletal activity in mice
Joaquin N Lugo1, Marjorie H Thompson2, Philippe Huber2
1Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA; Institute of Biomedical Sciences, Baylor University, Waco, TX 76798, USA.
Experimental Neurology
|February 7, 2017
Summary
Genetic epilepsy in mice lacking Pten leads to low bone mineral density and impaired bone mineralization. These findings suggest a link between epilepsy and increased fracture risk, independent of anti-seizure medications.
Area of Science:
- Bone biology
- Neuroscience
- Genetics
Background:
- Individuals with epilepsy face a higher risk of bone fractures.
- While anti-seizure medications are linked to low bone mineral density (BMD), the direct impact of seizures on bone health remains unclear.
Purpose of the Study:
- To investigate if seizures alter bone mass, morphology, and mineralization.
- To test this hypothesis in a genetic epilepsy model (NS-Pten knockout mice) and in mice experiencing status epilepticus.
Main Methods:
- Microcomputed tomography (microCT) was used to assess BMD, bone morphology, and mineralization in NS-Pten knockout and wildtype mice.
- Locomotion was measured to rule out hypoactivity as a cause for bone changes.
- Kainic acid-induced seizures were also studied in wildtype mice.
Main Results:
- NS-Pten knockout mice showed significantly lower BMD in the tibia compared to controls.
- These mice also exhibited altered bone morphology, including decreased trabecular bone and endocortical expansion.
- Reduced tissue mineral density in the midshaft indicated impaired bone mineralization. Hyperactivity was observed, excluding hypoactivity as a cause for bone deficits.
- No significant BMD differences were found after kainic acid-induced seizures or in the Kv4.2 knockout model.
Conclusions:
- Deletion of Pten in the brain leads to impaired bone mass and mineralization in mice.
- These bone deficits may contribute to an increased fracture risk in individuals with epilepsy.
- Epilepsy itself, independent of medication, may negatively impact bone health.

