PMID- 29933054
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 118
DP  - 2018 Oct
TI  - Imaging correlates of behavioral impairments: An experimental PET study in the 
      rat pilocarpine epilepsy model.
PG  - 9-21
LID - S0969-9961(18)30187-6 [pii]
LID - 10.1016/j.nbd.2018.06.010 [doi]
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 [(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) and 
      2'-methoxyphenyl-(N-2'-pyridinyl)-p-(18)F-fluoro-benzamidoethylpiperazine 
      ([(18)F]MPPF) as imaging correlates of neurobehavioral comorbidities in the 
      pilocarpine rat model of epilepsy. Findings from rats with epilepsy revealed a 
      regional reduction in [(18)F]FDG uptake indicating thalamic hypometabolism. In 
      addition, an increase in septal [(18)F]MPPF binding was observed in rats with 
      spontaneous recurrent seizures. Both thalamic [(18)F]FDG and septal [(18)F]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 [(18)F]FDG data. Moreover, thalamic [(18)F]FDG and septal 
      [(18)F]MPPF data exhibited a correlation with brain-derived neurotrophic factor 
      (BDNF) serum concentrations, which were lowered in rats with epilepsy. In 
      conclusion, muPET data from rats with pilocarpine-induced epileptogenesis indicate 
      altered septal 5-HT(1A) receptor binding. Further research is necessary assessing 
      whether septal 5-HT(1A) 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 [(18)F]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.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Di Liberto, Valentina
AU  - Di Liberto V
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - van Dijk, R Maarten
AU  - van Dijk RM
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - Brendel, Matthias
AU  - Brendel M
AD  - Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, 
      Germany.
FAU - Waldron, Ann-Marie
AU  - Waldron AM
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - Moller, Christina
AU  - Moller C
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - Koska, Ines
AU  - Koska I
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - Seiffert, Isabel
AU  - Seiffert I
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - Gualtieri, Fabio
AU  - Gualtieri F
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany.
FAU - Gildehaus, Franz Josef
AU  - Gildehaus FJ
AD  - Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, 
      Germany.
FAU - von Ungern-Sternberg, Barbara
AU  - von Ungern-Sternberg B
AD  - Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, 
      Germany.
FAU - Lindner, Magdalena
AU  - Lindner M
AD  - Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, 
      Germany.
FAU - Ziegler, Sibylle
AU  - Ziegler S
AD  - Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, 
      Germany.
FAU - Palme, Rupert
AU  - Palme R
AD  - Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, 
      Austria.
FAU - Hellweg, Rainer
AU  - Hellweg R
AD  - Department of Psychiatry and Psychotherapy, Charite, Berlin, Germany.
FAU - Gass, Peter
AU  - Gass P
AD  - Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, 
      University of Heidelberg, Mannheim, Germany.
FAU - Bartenstein, Peter
AU  - Bartenstein P
AD  - Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, 
      Germany.
FAU - Potschka, Heidrun
AU  - Potschka H
AD  - Institute of Pharmacology, Toxicology, and Pharmacy, 
      Ludwig-Maximilians-University, Munich, Germany. Electronic address: 
      potschka@pharmtox.vetmed.uni-muenchen.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180620
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Epilepsy/*chemically induced/*diagnostic imaging/metabolism
MH  - Female
MH  - *Interpersonal Relations
MH  - Mental Disorders/chemically induced/diagnostic imaging/metabolism
MH  - Pilocarpine/*toxicity
MH  - Positron-Emission Tomography/*methods
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Serotonin, 5-HT1A/metabolism
OTO - NOTNLM
OT  - Animal model
OT  - BDNF
OT  - Behavior
OT  - Epilepsy
OT  - PET
OT  - [(18)F]FDG
OT  - [(18)F]MPPF
EDAT- 2018/06/23 06:00
MHDA- 2019/09/10 06:00
CRDT- 2018/06/23 06:00
PHST- 2018/02/26 00:00 [received]
PHST- 2018/06/05 00:00 [revised]
PHST- 2018/06/12 00:00 [accepted]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/06/23 06:00 [entrez]
AID - S0969-9961(18)30187-6 [pii]
AID - 10.1016/j.nbd.2018.06.010 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2018 Oct;118:9-21. doi: 10.1016/j.nbd.2018.06.010. Epub 2018 Jun 
      20.