Biology subjects

Helin, S.

Publications and source records attributed to Helin, S..

10 recordsLinked to original sources

bioRxiv2026

Seasonal photoperiod cycling reduces inter-individual variability in mu-opioid receptor density in rats

RationaleThe -opioid receptor (MOR) is widely expressed across tissues and plays crucial roles in pain and stress responses, social behaviour, and immune regulation. Recent evidence indicates seasonal variation in in vivo MOR signalling; for example, short photoperiods are associated with reduced central MOR availability, increased MOR expression in brown adipose tissue (BAT), and strengthened brain-BAT interactions. However, despite this coupling with photoperiod, it remains unclear whether static daylength and dynamically changing photoperiods exert distinct effects, as adaptation to photoperiod transitions may itself induce stress-related modulation of the MOR system. Elucidating how seasonal, stress-related adaptations influence MOR signalling is essential for advancing our understanding of seasonal fluctuations in mood and stress regulation. MethodsWe compared rats housed under seasonal photoperiod cycling with those maintained under constant photoperiod conditions, using ex vivo radioligand binding to directly assess MOR density in central and peripheral tissues. ResultsRats exposed to seasonal photoperiod cycling showed markedly reduced inter-individual variability in MOR density in both the brain (including the cerebellum and striatum) and peripheral tissues (adrenal glands), whereas no tissues exhibited substantially increased variability. ConclusionsThese findings demonstrate that seasonal photoperiod cycling stabilizes MOR dynamics at the population level, suggesting stress-related synchronization of MOR signalling. The findings deepen our understanding of seasonal effects on endogenous MOR signalling, and further underscore the role of seasonal light variation in modulating mood-related processes.

neuroscience↗

bioRxiv2024

Endogenous opioid system modulates proximal and distal threat signals in the human brain

BACKGROUNDFear promotes rapid detection of threats and appropriate fight-or-flight responses. The endogenous opioid system modulates responses to pain and psychological stressors. Opioid agonists also have also anxiolytic effects. Fear and anxiety constitute major psychological stressors for humans, yet the contribution of the opioid system to acute human fear remains poorly characterized. METHODSWe induced intense unconditioned fear in the subjects by gradually exposing them to a living constrictor snake (threat trials) versus an indoor plant (safety trials). Brain haemodynamic responses were recorded from 33 subjects during functional magnetic resonance imaging (fMRI). In addition, 15 subjects underwent brain positron emission tomography (PET) imaging using [11C]carfentanil, a high affinity agonist radioligand for -opioid receptors (MORs). PET studies under threat or safety exposure were performed on separate days. Pupillary arousal responses to snake and plant exposure were recorded in 36 subjects. Subjective fear ratings were measured throughout the experiments. RESULTSSelf-reports and pupillometric responses confirmed significant experience of fear and autonomic activation during the threat trials. fMRI data revealed that proximity with the snake robustly engaged brainstem defense circuits as well as thalamus, dorsal attention network, and motor and premotor cortices. These effects were diminished during repeated exposures. PET data revealed that [11C]carfentanil binding to MORs was significantly higher during the fear versus safety condition, and the acute haemodynamic responses to threat were dependent on baseline MOR binding in the cingulate gyrus and thalamus. Finally, baseline MOR tone predicted dampening of the haemodynamic threat responses during the experiment. CONCLUSIONSPreparatory response during acute fear episodes involves a strong motor component in addition to the brainstem responses. These haemodynamic changes are coupled with a deactivation of the opioidergic circuit, highlighting the role of MORs in modulating the human fear response.

neuroscience↗

bioRxiv2024

Dopamine D2R and opioid MOR availability in autism spectrum disorder

Opioid and dopamine receptor systems are implicated in the pathoetiology of autism, but in vivo human brain imaging evidence for their role remains elusive. Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11C]raclopride (D2R) and [11C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 19 age and sex matched controls. Regional group differences in D2R and MOR receptor availabilities were tested with linear mixed models and associations between regional receptor availabilities were examined with correlations. There were no group differences in whole-brain voxel-wise analysis of DR2 but ROI analysis presented a lower overall mean D2R availability in striatum of the ASD versus control group. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens of the ASD group. The whole-brain voxel-wise analysis of MOR revealed precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens. These alterations may translate to disrupted modulation of social motivation and reward in ASD.

neuroscience↗

bioRxiv2023

Aberrant type 2 dopamine receptor availability in criminal psychopathy

BackgroundPsychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. MethodsHere we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n=11) and healthy matched controls (n=19) using positron emission tomography (PET). D2R were measured with radioligand [11C]raclopride and MORs with radioligand [11C]carfentanil. ResultsPsychopathic subjects had lowered D2R availability in caudate and putamen, and D2R striatal availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability amygdala and nucleus accumbens. ConclusionsWe conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for the aberrant MOR system is more limited.

neuroscience↗

bioRxiv2022

Endogenous opioid release following orgasm in man: A combined PET-fMRI study

Sex is one of the most rewarding and motivating behaviours for humans. Endogenous mu-opioid receptor system (MORs) plays a key role in the mammalian reward circuit. Both human and animal experiments suggest the involvements of MORs in human sexual pleasure, yet this hypothesis currently lacks in vivo support. We used positron emission tomography (PET) with the radioligand [11C]carfentanil, which has high affinity for MORs to quantify endogenous opioid release following orgasm in man. Subjects were scanned twice: Once immediately after reaching an orgasm and once in a baseline state. Haemodynamic activity was measured with functional magnetic resonance imaging during penile stimulation from partner. The PET data revealed significant opioid release in hippocampus. Haemodynamic activity in somatosensory and motor cortices as well as hippocampus and thalamus increased during penile stimulation, and thalamic activation was linearly dependent on self-reported sexual arousal. Altogether these data show that endogenous opioidergic activation in the medial temporal lobe is centrally involved in sexual arousal.

neuroscience↗

bioRxiv2022

APOE ε4 gene dose effect on imaging and blood biomarkers of glial reactivity and β-amyloid pathology

Increased reactivity of microglia and astrocytes is known to be present at various stages of the Alzheimers continuum but their relationship with core Alzheimers disease pathology in the preclinical stages is less clear. We investigated glial reactivity and {beta}-amyloid pathology in cognitively unimpaired APOE {varepsilon}4 homozygotes, heterozygotes and non-carriers using 11C-PK11195 PET (targeting 18-kDa translocator protein), 11C-PiB PET (targeting {beta}-amyloid), brain MRI, and a preclinical cognitive composite (APCC). Plasma glial fibrillary acidic protein (GFAP) by and plasma A{beta}1-42/1-40 were measured using single molecule array and immunoprecipitation combined with mass spectrometry, respectively. We observed that (i) 11C-PiB-binding was significantly higher in APOE {varepsilon}4 homozygotes compared with non-carriers in all evaluated regions, (ii) regional 11C-PK11195-binding did not differ between the APOE {varepsilon}4 gene doses or between A{beta}-positive and -negative individuals, and (iii) higher 11C-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, and elevated 11C-PiB-binding and plasma GFAP concentration with lower APCC scores. Increased glial reactivity might emerge in later stages of preclinical Alzheimers disease in parallel with early neurodegenerative changes.

neuroscience↗

bioRxiv2022

Photoperiod modulates mu-opioid receptor availability in brown adipose tissue

Photoperiod drives metabolic activity of brown adipose tissue (BAT), and affects food intake and weight gain in mammals. Sympathetic innervation in BAT controls thermogenesis and facilitates physiological adaption to seasons, but the exact mechanism remains elusive. Previous studies show that the central opioid signaling tunes BAT heating and the brain muopioid receptor (MOR) levels have seasonal patterns. It is hence intriguing to know whether the peripheral MOR signaling shows seasonal variation. Here, we examined the effect of photoperiod on BAT MOR availability using [11C]carfentanil positron emission topography (PET). Adult rats (n = 9) were repeatedly imaged under changing photoperiods which simulates the local seasons. Long photoperiod downregulated MOR availability in BAT, while MOR availability in the muscles was unaffected. We confirmed the expression of MOR in BAT and muscle using immunofluorescence imaging. We conclude that photoperiod causally affects MOR availability in BAT, and sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. Significance of the studyPhotoperiod impacts the metabolic activity of brown adipose tissue (BAT) with the exact mechanism still unclear. The current study shows that photoperiod causally affects the mu-opioid receptor (MOR) levels in BAT, with longer photoperiod leading to lower MOR availability. This possibly indicates down-regulated innervation during bright seasons. Immunofluorescence staining data reveal expression of MOR in both brain and peripheral tissues, drawing attention to the under-investigated peripheral MOR system. Also, the study highlights the feasibility of [11C]carfentanil PET in studying the peripheral MOR signaling.

molecular biology↗

bioRxiv2020

Mesolimbic opioid-dopamine interaction is disrupted in obesity but recovered by weight loss following bariatric surgery

BackgroundObesity is a growing burden to health and economy worldwide. Obesity is associated with central -opioid receptor (MOR) downregulation, and the interaction between MOR and dopamine D2 receptor (D2R) system in the ventral striatum is disrupted among obese subjects. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying subjects undergoing surgical weight loss (bariatric surgery) procedure. MethodsWe recruited 20 healthy non-obese (mean BMI 22) and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability was measured using positron emission tomography (PET) with [11C]carfentanil and [11C]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed to obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. ResultsIn the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but unaltered association in dorsal caudate (r = .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss (mean total weight loss 22 %). ConclusionsBariatric surgery and concomitant weight loss recovers the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioural interventions for treating obesity. Clinical Trials RegistrationSleevePET2, NCT01373892, http://www.clinicaltrials.gov

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

Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre PBR28 HRRT PET study

PurposeTo investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [11C]PBR28. Methods[11C]PBR28 data from 140 healthy volunteers (72 males and 68 females; n=78 with HAB and n=62 MAB genotype; age range 19-80 years; BMI range 17.6 - 36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (n=53), Turku PET centre (n=62) and Yale University PET Center (n=25). The total volume of distribution (VT) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. ResultsThere were significant positive correlations between age and VT in the frontal and temporal cortex. BMI showed a significant negative correlation with VT in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher VT. A subgroup analysis revealed a positive correlation between VT and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. ConclusionThese findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.

immunology↗