Dataset Information

Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender.

ABSTRACT: Previous research reported an age-related decline in brain norepinephrine transporter (NET) using (S, S)-[11C]O-methylreboxetine ([11C]MRB) as a radiotracer. Studies with the same tracer have been mixed in regard to differences related to body mass index (BMI). Here, we investigated potential age-, BMI-, and gender-related differences in brain NET availability using [11C]MRB, the most selective available radiotracer. Forty-three healthy participants (20 females, 23 males; age range 18-49 years), including 12 individuals with normal/lean weight, 15 with overweight, and 16 with obesity were scanned with [11C]MRB using a positron emission tomography (PET) high-resolution research tomograph (HRRT). We evaluated binding potential (BP_ND ) in brain regions with high NET availability using multilinear reference tissue model 2 (MRTM2) with the occipital cortex as a reference region. Brain regions were delineated with a defined anatomic template applied to subjects' structural MR scans. We found a negative association between age and NET availability in the locus coeruleus, raphe nucleus, and hypothalamus, with a 17%, 19%, and 14% decrease per decade, respectively, in each region. No gender or BMI relationships with NET availability were observed. Our findings suggest an age-related decline, but no BMI- or gender-related differences, in NET availability in healthy adults.

SUBMITTER: Koohsari S

PROVIDER: S-EPMC10416616 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender.

Koohsari Sheida S Sadabad Faranak Ebrahimian FE Pittman Brian B Gallezot Jean-Dominque JD Carson Richard E RE van Dyck Christopher H CH Li Chiang-Shan R CR Potenza Marc N MN Matuskey David D

Synapse (New York, N.Y.) 20230629 5

Previous research reported an age-related decline in brain norepinephrine transporter (NET) using (S, S)-[11C]O-methylreboxetine ([11C]MRB) as a radiotracer. Studies with the same tracer have been mixed in regard to differences related to body mass index (BMI). Here, we investigated potential age-, BMI-, and gender-related differences in brain NET availability using [11C]MRB, the most selective available radiotracer. Forty-three healthy participants (20 females, 23 males; age range 18-49 years), ...[more]

PMID: 37382240

Similar Datasets

Project description:Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder. The norepinephrine transporter (NET) inhibitor atomoxetine, the first nonstimulant drug licensed for ADHD treatment, also acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist. The compound's effects on gene expression and protein levels of NET and NMDAR subunits (1, 2A, and 2B) are unknown. Therefore, adolescent Sprague Dawley rats were treated with atomoxetine (3 mg/kg, intraperitoneal injection [i.p.]) or saline (0.9%, i.p.) for 21 consecutive days on postnatal days (PND) 21-41. In humans, atomoxetine's earliest clinical therapeutic effects emerge after 2-3 weeks. Material from prefrontal cortex, striatum (STR), mesencephalon (MES), and hippocampus (HC) was analyzed either directly after treatment (PND 42) or 2 months after termination of treatment (PND 101) to assess the compound's long-term effects. In rat brains analyzed immediately after treatment, protein analysis exhibited decreased levels of the NET in HC, and NMDAR subunit 2B in both STR and HC; the transcript levels were unaltered. In rat brains probed 2 months after final atomoxetine exposure, messenger RNA analysis also revealed significantly reduced levels of genes coding for NMDAR subunits in MES and STR. NMDAR protein levels were reduced in STR and HC. Furthermore, the levels of two SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, synaptophysin and synaptosomal-associated protein 25, were also significantly altered in both treatment groups. This in vivo study detected atomoxetine's effects beyond NET inhibition. Taken together, these data reveal that atomoxetine seems to decrease glutamatergic transmission in a brain region-specific manner. Long-term data show that the compound's impact is not due to an acute pharmacological effect but lasts or even amplifies after a drug-free period of 2 months, leading to altered development of synaptic composition. These alterations might contribute to atomoxetine's clinical effects in the treatment of ADHD, a neurodevelopmental disorder in which synaptic processes and especially a dysregulated glutamatergic metabolism seem to be involved.

Project description:IntroductionThe incidence of pediatric urolithiasis has been increasing over the years; however, the etiology of this increase is not well understood. Age, body mass index, and gender have been examined as possible risk factors for stone disease, but with inconsistent and variable associations.ObjectiveWe aim to investigate the urine chemistry factors, as assessed by 24-h urinary parameters, in pediatric stone formers at a large volume tertiary referral center in the highest areas in the United States, the Southeast, based on age, body mass index, and gender.Study designWe retrospectively reviewed all pediatric stone formers who completed a 24-h study between 2005 and 2016. Patients were stratified by age (3-10 versus 11-18 years of age), overweight status (above versus below the 85th percentile for body mass index), and gender (male versus female) (Summary Figure). Statistical analysis included analysis of variance and logistic regression.Results243 patients were included in our analysis. Patients in the first decade of life were found to have greater numbers of urinary risk factors than those in the second decade. Non-overweight patients were more likely to have hyperoxaluria and hyperuricosuria, while overweight patients were more likely to have hypocitraturia. Female patients were more likely to have higher hyperoxaluria, while male patients were more likely to have hypercalciuria.DiscussionIn contrast to prior publications, obesity is not linked to increased risk of urolithiasis with non-overweight individuals having a greater number of risk factors than the overweight cohort. Despite stone disease being more prevalent in adolescents, the greatest number of risk factors were present in the first decade of life. Lastly, female children had more urinary risk factors than males. Further understanding of the underlying causes of stone disease in various pediatric populations is warranted.ConclusionWhile more urinary risk factors were identified in younger, non-overweight, and female patients, there remains no consensus on the urinary risk factors for pediatric urolithiasis. Further study is needed to elucidate the risk factors and pathophysiology of pediatric stone disease.

Dataset Information

Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender.

Publications

Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets