NECAB2 is an endosomal protein important for striatal function.

Synaptic signaling depends on ATP generated by mitochondria. Dysfunctional mitochondria shift the redox balance towards a more oxidative environment. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction.

Additional Assessment of Fecal Corticosterone Metabolites Improves Visual Rating in the Evaluation of Stress Responses of Laboratory Rats.

Since animal experiments cannot be completely avoided, the pain, suffering, and distress of laboratory animals must be minimized. To this end, a major prerequisite is reliable assessment of pain and distress. Usually, evaluation of animal welfare is done by visual inspection and score sheets.

Image-Derived Input Functions for Quantification of A Adenosine Receptors Availability in Mice Brains Using PET and [F]CPFPX.

Purpose: imaging for the A adenosine receptors (AARs) with positron emission tomography (PET) using 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propylxan- thine ([F]CPFPX) has become an important tool for studying physiological processes quantitatively in mice. However, the measurement of arterial input functions (AIFs) on mice is a method with restricted applicability because of the small total blood volume and the related difficulties in withdrawing blood. Therefore, the aim of this study was to extract an appropriate [F]CPFPX image-derived input function (IDIF) from dynamic PET images of mice.

Influence of binding affinity and blood plasma level on cerebral pharmacokinetics and PET imaging characteristics of two novel xanthine PET radioligands for the A adenosine receptor.

Introduction: The suitability of novel positron emission tomography (PET) radioligands for quantitative in vivo imaging is affected by various physicochemical and pharmacological parameters. In this study, the combined effect of binding affinity, lipophilicity, protein binding and blood plasma level on cerebral pharmacokinetics and PET imaging characteristics of three xanthine-derived A adenosine receptor (AAR) radioligands was investigated in rats.

Methods: A comparative evaluation of two novel cyclobutyl-substituted xanthine derivatives, 8-cyclobutyl-3-(3-[F]fluoropropyl)-1-propylxanthine ([F]CBX) and 3-(3-[F]fluoropropyl)-8-(1-methylcyclobutyl)-1-propylxanthine ([F]MCBX), with the reference AAR radioligand 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propylxanthine ([F]CPFPX) was conducted.

Relevance of In Vitro Metabolism Models to PET Radiotracer Development: Prediction of In Vivo Clearance in Rats from Microsomal Stability Data.

The prediction of in vivo clearance from in vitro metabolism models such as liver microsomes is an established procedure in drug discovery. The potentials and limitations of this approach have been extensively evaluated in the pharmaceutical sector; however, this is not the case for the field of positron emission tomography (PET) radiotracer development. The application of PET radiotracers and classical drugs differs greatly with regard to the amount of substance administered.

Effects of Long-Term Caffeine Consumption on the Adenosine A Receptor in the Rat Brain: an In Vivo PET Study with [F]CPFPX.

Purpose: Caffeine, a nonselective antagonist of adenosine receptors, is the most popular psychostimulant worldwide. Recently, a protective role of moderate chronic caffeine consumption against neurodegenerative diseases such as Alzheimer's and Parkinson's disease has been discussed. Thus, aim of the present study was an in vivo investigation of effects of long-term caffeine consumption on the adenosine A receptor (AAR) in the rat brain.

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D R binding and reduces striatal D R binding in male hemiparkinsonian rats.

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7).

Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain.

The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague-Dawley rats.