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Di Liberto, Valentina; Dijk, R. Maarten van; Brendel, Matthias; Waldron, Ann-Marie; Möller, Christina; Koska, Ines; Seiffert, Isabel; Gualtieri, Fabio; Gildehaus, Franz Josef; Ungern-Sternberg, Barbara von; Lindner, Magdalena; Ziegler, Sibylle; Palme, Rupert; Hellweg, Rainer; Gass, Peter; Bartenstein, Peter; Potschka, Heidrun (2018): Imaging correlates of behavioral impairments: An experimental PET study in the rat pilocarpine epilepsy model. In: Neurobiology of Disease, Vol. 118: pp. 9-21
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Abstract

Psychiatric comorbidities are prevalent in patients with epilepsy and greatly contribute to the overall burden of disease. The availability of reliable biomarkers to diagnose epilepsy-associated comorbidities would allow for effective treatment and improved disease management. Due to their non-invasive nature, molecular imaging techniques such as positron emission tomography (PET) are ideal tools to measure pathologic changes. In the current study we investigated the potential of [F-18]fluoro-2-deoxy-o-glucose ([F-18]FDG) and 2'-methoxyphenyl(N-2'-pyridinyl)-p-F-18-fluoro-benzamidoethylpiperazine ([F-18]MPPF) as imaging correlates of neurobehavioral comorbidities in the pilocarpine rat model of epilepsy. Findings from rats with epilepsy revealed a regional reduction in [F-18]FDG uptake indicating thalamic hypometabolism. In addition, an increase in septal [F-18]MPPF binding was observed in rats with spontaneous recurrent seizures. Both thalamic [F-18]FDG and septal [F-18]MPPF data proved to correlate with behavioral alterations including decreases in luxury behavior such as burrowing and social interaction, and changes in behavioral patterns in anxiety tests. A correlation with seizure frequency was confirmed for thalamic [F-18]FDG data. Moreover, thalamic [F-18]FDG and septal [F-18]MPPF data exhibited a correlation with brain-derived neurotrophic factor (BDNF) serum concentrations, which were lowered in rats with epilepsy. In conclusion, mu PET data from rats with pilocarpine-induced epileptogenesis indicate altered septal 5-HT1A receptor binding. Further research is necessary assessing whether septal 5-HT1A receptor binding may serve as an imaging correlate of neuropsychiatric comorbidities in epilepsy patients and for severity assessment in rodent epilepsy models. In contrast, we obtained evidence that [F-18]FDG uptake also reflects the severity of epilepsy and, thus, might not constitute a biomarker with sufficient specificity for psychiatric comorbidities. Evidence has been obtained that BDNF might serve as a peripheral circulatory biomarker. Further experimental and clinical assessment is necessary for validation of the marker candidates.