Biology subjects

Chaudhari, A. J.

Publications and source records attributed to Chaudhari, A. J..

5 recordsLinked to original sources

bioRxiv2026

Kappa Opioid-Oxytocin Interactions During Long-Term Partner Separation: Insights from PET Imaging in Titi Monkeys (Plecturocebus cupreus)

Social bonds are fundamental to health and well-being, and their disruption through partner separation is associated with significant physiological and psychological consequences. The kappa opioid receptor (KOR) system has been proposed as a key modulator of oxytocin (OT) release during partner separation, with prolonged separation hypothesized to trigger KOR downregulation in the paraventricular nucleus of the hypothalamus that disinhibits OT release over time (Bales & Rogers, 2022). However, this model has been difficult to assess non-invasively in primates. The present study used positron emission tomography (PET) with the KOR-selective radiotracer [11C]GR103545 to examine KOR availability in vivo across brain regions implicated in social bonding and separation distress in 16 pair-bonded titi monkeys using a within-subject two-week separation paradigm. Plasma OT, cerebrospinal fluid OT, and plasma cortisol were collected at each scan as complementary indices of peripheral and central OT signaling and physiological stress. We hypothesized that long-term separation would downregulate KORs in the hypothalamus and pituitary, indexed by reduced non-displaceable binding potential (BPND), consistent with the Bales and Rogers model, and increase plasma OT consistent with KOR downregulation disinhibiting OT release. Partner separation significantly elevated plasma cortisol in both sexes, confirming the physiological stress of the manipulation. A significant Condition x Sex interaction was observed for plasma OT, reflecting a crossover pattern in which males, who had significantly higher plasma OT than females at baseline, showed a significant decrease during separation while females showed a non-significant increase, though the sex difference during separation did not reach significance. KOR availability was significantly reduced in the nucleus accumbens during separation, with a non-significant trend toward reduction in the anterior cingulate cortex, while no significant condition effects were observed in the remaining a priori chosen regions. No significant sex effects or Condition x Sex interactions were observed in any a priori chosen PET region. Together, these findings provide the first in vivo neuroimaging evidence of KOR system engagement during partner separation in a pair-bonded primate species, and reveal a sex-dependent OT response to separation that extends and adds nuance to the Bales and Rogers (2022) framework.

neuroscience↗

bioRxiv2026

Brain Kappa Opioid Receptor Availability Across Stress and Social Buffering Conditions: A Positron Emission Tomography Study in Coppery Titi Monkeys

Social connectedness strongly influences health and longevity, and adult pair bonds provide psychological benefits distinct from other social relationships. Oxytocin (OT), corticotropin-releasing hormone (CRH), and opioids, play an important role in the formation and maintenance of pair bonds. Evidence suggests that OT modulates the stress response via the hypothalamic-pituitary-adrenal (HPA) axis, while the kappa ({kappa}) opioid system interacts with and may modulate OT signaling in contexts of stress and separation. In this study 20 coppery titi monkeys were exposed to a physical stressor under three social conditions: baseline (no stressor, partner present), stress (stressor, no partner present) and buffering (stressor, partner present). We predicted stress-induced dynorphin release would reduce {kappa}-opioid receptor availability measured via [{superscript 1}{superscript 1}C]GR103545 Positron Emission Tomography (PET) and lower cerebrospinal fluid (CSF) OT, whereas partner presence would mitigate dynorphin release and increase CSF OT, with reduced dynorphin inferred from higher {kappa}-opioid receptor radioligand binding. Our results show condition-dependent differences in [{superscript 1}{superscript 1}C]GR103545 binding in several brain regions, including the amygdala and hippocampus, with altered binding in both the stress and social buffering conditions. Cortisol levels were elevated in the stress condition compared to baseline. Females exhibited lower CSF OT levels during stress than at baseline, whereas plasma OT levels did not differ across conditions or between sexes. Spearman correlations revealed no significant associations between plasma and CSF OT. Together, these findings highlight the complex interaction between {kappa}-opioid signaling, OT, and HPA axis activity in the context of social relationships and highlight neuroendocrine mechanisms underlying stress regulation in pair-bonded species.

neuroscience↗

bioRxiv2024

Mapping Kappa Opioid Receptor Binding in Titi Monkeys with 11C-GR103545 PET

PurposeThe kappa opioid receptor (KOR) plays a pivotal role in stress- and anxiety-related behaviors, especially in social separation and bonding. However, KOR modulations in these social contexts are not fully characterized. The coppery titi monkey (Plecturocebus cupreus) has been utilized as a translational animal model for studying the neurobiology of attachment, as they form socially monogamous adult pair bonds. While the PET radiotracer 11C-GR103545 has shown the ability to track KOR activity in other species, it has not been utilized in titi monkeys. This study assessed 11C-GR103545 PET for characterizing KOR activity in vivo and its pharmacological blockade in titi monkeys. MethodsAdult titi monkeys (N=6) underwent 11C-GR103545 PET brain scans at baseline, followed by repeat scans upon administration of a KOR antagonist (CERC-501) and a KOR agonist (U50,488). Region-specific, non-displaceable binding potential (BPND) was calculated, with the cerebellum as the reference region, focusing on 14 brain volumes of interest (VOIs) implicated in social bonding. ResultsBaseline 11C-GR103545 uptake characteristics across VOIs were consistent with previous reports in humans and other monkey models. CERC-501 pretreatment led to a significant reduction in BPND (average 55.99%) across several, but not all brain VOIs, with the most notable reduction in the superior frontal gyrus (76.25%). In contrast, U50,488 pretreatment resulted in no significant BPND changes across the VOIs analyzed. ConclusionsThis study demonstrates the utility of 11C-GR103545 to assess KOR binding dynamics in a monkey model of social bonding. Region-specific blockade of KOR was observed after pretreatment by CERC-501, while blockade by the KOR agonist U50,488 did not change 11C-GR103545 binding.

neuroscience↗

bioRxiv2018

Skeletal Muscle Metrics on Clinical 18F- FDG PET/CT Predict Health Outcomes in Patients with Sarcoma

The aim of this study was to determine the association of measures of skeletal muscle determined from 18F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18F-FDG PET/CT is associated with outcomes and serum hemoglobin and albumin in patients with sarcoma.

bioengineering↗

bioRxiv2018

Sex-dependent Relationship Between Wrist Deviation and Scaphoid Kinematics

Several methods of describing patterns of carpal kinematics from radiographs have emerged due to their potential use in developing personalized treatments for wrist pathologies. Such radiography-derived metrics have been used to infer associations between patterns of scaphoid kinematics and other clinically relevant factors such as sex, but the simultaneous effects of sex and wrist position on scaphoid kinematic metrics has yet to be considered. We sought to investigate the relationship between wrist position in the coronal plane and radiographic measurements of the scaphoid for each sex independently, then identify sex-specific differences in scaphoid measurements and calculated metrics. We retrospectively identified 38 subjects with posteroanterior radial and ulnar deviation radiographs. Radiographic scaphoid measurements were collected and used to calculate five scaphoid kinematic metrics per participant. We used Pearson correlation coefficients to explore the relationships between the degrees of wrist deviation in the coronal plane and radiographic scaphoid measurements for men and women independently. We used the non-parametric Wilcoxon signed-rank test to compare values between sexes. The correlations between degrees of coronal wrist deviation and radiographic measurements of scaphoid inclination were significant only for men. Men also had significantly greater values for all radiographic scaphoid measurements. Our study demonstrated sex-specific differences in the relationship between the degrees of radial and ulnar wrist deviation and scaphoid positioning.\n\nClinical RelevanceOur findings show the importance of stratifying by sex in studies of carpal kinematics, such as scaphoid kinematics, and that investigation of strategies to restore normal carpal function should incorporate sex as a biological variable.

physiology↗