Altered PI3K/mTOR Signaling within the Forebrain Leads to Respiratory Deficits in a Mouse Model of Epilepsy
Year: 2025
Type: article
Abstract: People with epilepsy may experience sudden death due to respiratory failure through mechanisms that are currently not well understood. Epilepsy causing mutations are thought to elicit seizures due to altered function of forebrain circuits, yet breathing is controlled largely by the brainstem. To investigate how altered forebrain activity could impact breathing, we examined respiratory and seizure phenotypes in a mouse epilepsy model with a forebrain-specific deletion of the phosphatase and tensin homolog ( Pten ) gene. Using chronic diaphragm electromyography and cortical electroencephalography, we monitored Pten conditional knock-out (PTEN–cKO) mice (six males and four females) and control littermates (six males and three females) continuously from preseizure onset through end-stage disease. PTEN–cKO mice develop spontaneous seizures that progress in frequency with age, accompanied by gradual changes in respiratory function, even during interictal periods. As seizure burden increases, PTEN–cKO mice experience an increased frequency of interictal apneas, slowing of respiratory rhythm, prolongation of inspiratory bursts, and elevation of inspiratory effort. All animals experienced a terminal apnea prior to cardiac arrest. These findings demonstrate that P ten deletion in the forebrain disrupts the control of breathing and leads to terminal respiratory failure.
Source: eNeuro
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,925
OpenAlex ID: W4416872471