Biology subjects

Kantonen, T.

Publications and source records attributed to Kantonen, T..

6 recordsLinked to original sources

bioRxiv2022

The predictive power of mRNA mapping for Cannabinoid 1 receptor protein in the human brain

Type 1 cannabinoid (CB1) receptor is expressed in cortex, hippocampus, amygdala, basal ganglia, and cerebellum. With the help of the Allen Human Brain Atlas, genomic maps visualize not only the gene expression across whole brain regions, but also the functional profile of brain structures. Therefore, it is more timely than ever to integrate genomic mapping from brain mRNA atlas with the protein expression from positron emission tomography (PET) scans for better understanding of CB1 receptor of the human brain. F18-FMPEP-d2 PET scans were retrieved from the AIVO neuroinformatics project. Autoradiography data were based on the study with H3-CP55940. mRNA expressions of CNR1 gene (Cannabinoid receptor 1) were downloaded from the Allen Human Brain Atlas. Volume of distribution (VT) from F18-FMPEP-d2 PET scans, CNR1 gene expression, and H3-CP55940 binding were calculated and Spearman correlation analysis was performed. Also, a meta-analysis was done to investigate the association between protein expression from PET and mRNA expression from the Allen Human Brain Atlas. Between VT of F18-FMPEP-d2 PET scans and CNR1 mRNA expression, moderate strength of correlation was observed (rho = 0.5026, p = 0.0354). Strong positive correlation was also found between CNR1 mRNA expression and H3-CP55940 binding (rho = 0.6727, p = 0.0281), validating the finding between F18-FMPEP-d2 PET scans and CNR1 mRNA. From the meta-analysis, the correlation coefficient ranged from -0.46 to 0.99, with a pooled effect of 0.58. In conclusion, the moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression. From the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains. HIGHLIGHTSO_LIWe investigated the association between CNR1 gene expression from the Allen Human Brain Atlas and type 1 cannabinoid (CB1) receptor expression from F18-FMPEP-d2 PET scans. C_LIO_LIThe moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression. C_LIO_LIFrom the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains. C_LI

neuroscience↗

bioRxiv2021

Endogenous μ-opioid receptor system modulates sex drive in human males

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. Here we measured healthy male subjects (n=52) brains MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n=108) provided limited evidence for association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.

neuroscience↗

bioRxiv2020

Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior

Eating behavior varies greatly between healthy individuals, but the neurobiological basis of these trait-like differences in feeding remains unknown. Central {micro}-opioid receptors (MOR) and cannabinoid CB1-receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brains opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2 scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating - individuals with low MORs reported being more likely to eat in response to environments palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically and functionally in the brain, they have distinct roles in mediating individual feeding patterns.

neuroscience↗

bioRxiv2020

Seasonal variation in brain mu-opioid receptor availability

Seasonal rhythms influence mood and sociability. The brain -opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. Here, we studied the seasonal effects on brain MOR availability via analysing a dataset (n=204) of [11C]carfentanil positron emission tomography (PET) scans of healthy volunteers. We found that seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability. Brain regions sensitive to daylength spanned the socio-emotional brain circuits, where MOR availability formed a spring-like peak. Causal effect of daylength on brain MOR availability was further verified by a post hoc experiment with repeated PET imaging of rats (n=9) under seasonal photoperiodic simulation. Therefore, the in vivo brain MOR availability in normal humans shows significant seasonal variation, which aligns with expected seasonal variation in mood and suicidality.

neuroscience↗

bioRxiv2019

Interindividual variability and lateralization of μ-opioid receptors in the human brain

The brains {micro}-opioid receptors (MORs) are involved in analgesia, reward and mood regulation. Several neuropsychiatric diseases have been associated with dysfunctional MOR system, and there is also considerable variation in receptor density among healthy individuals. Sex, age, body mass and smoking have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. Here we quantified in vivo MOR availability in the brains of 204 individuals with no neurologic or psychiatric disorders using positron emission tomography (PET) with tracer [11C]carfentanil. We then used Bayesian hierarchical modeling to estimate the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential. We also examined hemispheric lateralization of MOR availability. Age had regionally specific effects on MOR availability, with age-dependent increase in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders.

neuroscience↗

bioRxiv2019

Magia: Robust automated modeling and image processing toolbox for PET neuroinformatics

IntroductionModelling of the radioactivity images produced by PET scanners into biologically meaningful quantities, such as binding potential, is a complex multi-stage process involving data retrieval, preprocessing, drawing reference regions, kinetic modelling, and post-processing of parametric images. The process is challenging to automatize mainly because of manual work related to input generation, thus prohibiting large-scale standardized analysis of brain PET data. To resolve this problem, we introduce the Magia pipeline that enables processing of brain PET data with minimal user intervention. We investigated the accuracy of Magia in the automatic brain-PET data processing with four tracers binding to different binding sites: [11C]raclopride, [11C]carfentanil, [11C]MADAM, and [11C]PiB.\n\nMaterials and methodsFor each tracer, we processed 30 historical control subjects data with manual and automated methods. Five persons manually delineated the reference regions (cerebellar or occipital cortex depending on tracer) for each subject according to written and visual instructions. The automatic reference-region extraction was based on FreeSurfer parcellations. We first assessed inter-operator variance resulting from manual delineation of reference regions. Then we compared the differences between the manually and automatically produced reference regions and the subsequently obtained metrics.\n\nResultsThe manually delineated reference regions were remarkably different from each other. The differences translated into differences in outcome measures (binding potential or SUV-ratio), and the intra-class correlation coefficients were between 47 % and 96 % for the tracers. While the Magia-derived reference regions were topographically very different from the manually defined reference regions, Magia produced outcome measures highly consistent with average of the manually obtained estimates. For [11C]carfentanil and [11C]PiB there was no bias, while for [11C]raclopride and [11C]MADAM Magia produced 3-5 % higher binding potentials as a result of slightly lower time-integrals of reference region time-activity curves.\n\nConclusionEven if Magia produces reference regions that are anatomically different from manually drawn reference regions, the resulting outcome measures are highly similar. Based on these results and considering the high inter-operator variance of the manual method, the high level of standardization and strong scalability of Magia, we conclude that Magia can be reliably used to process brain PET data.

neuroscience↗