TY - JOUR
T1 - Imaging correlates of behavioral impairments: An experimental PET study in the rat pilocarpine epilepsy model
AU - Di Liberto, Valentina
AU - Di Liberto, Valentina
AU - Ziegler, Sibylle
AU - Gualtieri, Fabio
AU - Palme, Rupert
AU - Van Dijk, R. Maarten
AU - Waldron, Ann-Marie
AU - Brendel, Matthias
AU - Von Ungern-Sternberg, Barbara
AU - Möller, Christina
AU - Lindner, Magdalena
AU - Koska, Ines
AU - Seiffert, Isabel
AU - Gildehaus, Franz Josef
AU - Potschka, Heidrun
AU - Hellweg, Rainer
AU - Bartenstein, Peter
AU - Gass, Peter
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/349164
UR - http://www.elsevier.com/inca/publications/store/6/2/2/9/2/3/index.htt
M3 - Article
VL - 118
SP - 9
EP - 21
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -