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RESEARCH PRODUCT

Imaging and biochemical biomarkers of psychiatric comorbidities in a rat epilepsy model

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Aims: Biomarkers of epilepsy-associated psychiatric comorbidities represent a powerful tool for an early diagnosis and personalized therapy in patients with epilepsy. Here, in order to identify new candidates as biomarkers of epilepsy comorbidities, alterations in brain metabolic activity and serotonergic neurotransmission in a rat post-status epilepticus model were explored and cross-correlated with alterations in various neurobehavioral and biochemical parameters. Methods: Status epilepticus was induced in twelve female Sprague Dawley rats by lithium chloride-pilocarpine treatment. µPET analysis to determine [18F]FDG uptake and [18F]MPPF binding were performed in the chronic phase of epilepsy, followed by the assessment of alterations in several behavioral paradigms and biochemical markers. A Spearman cross-correlation analysis was performed including all µPET, behavioral and biochemical data. Results: Epileptic rats showed a reduction in thalamic [18F]FDG uptake, indicating regional hypometabolism, and increased septal [18F]MPPF binding suggesting changes in serotoninergic neurotransmission. Both, thalamic [18F]FDG and septal [18F]MPPF data correlate with behavioral alterations including decreases in burrowing behavior, in social interaction, and changes in anxiety-related behaviors. Moreover, thalamic [18F]FDG correlate with seizure frequency. Importantly, thalamic [18F]FDG and septal [18F]MPPF data correlate with BDNF serum levels, which were decreased in epileptic rats. Conclusions: µPET data suggest that alterations in septal 5HT1a receptor binding can be employed as imaging biomarker of epilepsy-associated neuropsychiatric comorbidities, as well as BDNF, which might be used as a peripheral circulatory biomarker. In contrast [18F]FDG uptake, which reflects epilepsy severity, might not represent a specific biomarker for psychiatric comorbidities. Project supported by Deutsche Forschungsgemeinschaft grants (FOR 2591, GZ: PO681/9-1)