Imaging correlates of behavioral impairments: An experimental PET study in the rat pilocarpine epilepsy model

Valentina Di Liberto, Valentina Di Liberto, Sibylle Ziegler, Fabio Gualtieri, Rupert Palme, R. Maarten Van Dijk, Ann-Marie Waldron, Matthias Brendel, Barbara Von Ungern-Sternberg, Christina Möller, Magdalena Lindner, Ines Koska, Isabel Seiffert, Franz Josef Gildehaus, Heidrun Potschka, Rainer Hellweg, Peter Bartenstein, Peter Gass

Risultato della ricerca: Articlepeer review

16 Citazioni (Scopus)


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 [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and 2′-methoxyphenyl-(N-2′-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine ([18F]MPPF) as imaging correlates of neurobehavioral comorbidities in the pilocarpine rat model of epilepsy. Findings from rats with epilepsy revealed a regional reduction in [18F]FDG uptake indicating thalamic hypometabolism. In addition, an increase in septal [18F]MPPF binding was observed in rats with spontaneous recurrent seizures. Both thalamic [18F]FDG and septal [18F]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 [18F]FDG data. Moreover, thalamic [18F]FDG and septal [18F]MPPF data exhibited a correlation with brain-derived neurotrophic factor (BDNF) serum concentrations, which were lowered in rats with epilepsy. In conclusion, μPET 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 [18F]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.
Lingua originaleEnglish
pagine (da-a)9-21
Numero di pagine13
RivistaNeurobiology of Disease
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

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