Circulating leptin, cortisol and gender differences associated with anorexia or obesity in depression

Haleem, Darakhshan Jabeen; Gul, Sumera

doi:10.1080/15622975.2019.1648870

Cited by 12 publications

(6 citation statements)

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“…Interaction of genetic and environmental factors is therefore thought to play a role in the development and precipitation of ADHD. Stress, as one of the aversive environmental factors, has been found to activate the hypothalamic-pituitary-adrenal (HPA) axis to increase the circulating level of glucocorticoids (GCs) (e.g., cortisol in humans) ( Corominas et al, 2012 ; Haleem and Gul, 2020 ). However, we and some other research groups have found a low level of plasma cortisol in ADHD children, indicating the hypo-responsiveness of the HPA axis in ADHD children and suggesting the close relationship between cortisol and the symptoms of attention deficit, hyperactivity, and impulsive behavior ( Ma et al, 2011 ; Pinto et al, 2016 ; Angeli et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Disturbed relationship between glucocorticoid receptor and 5-HT1AR/5-HT2AR in ADHD rats: A correlation study

Lin

Huang

et al. 2023

Front. Neurosci.

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ObjectiveThis work is to investigate the alterations of the central 5-hydroxytryptamine (5-HT) system in spontaneously hypertensive rats (SHR) and the correlation with the behaviors of SHR, and to explore the effects of glucocorticoid intervention on the central 5-HT system and SHR behaviors.Materials and methodsThree weeks old SHR were chosen as the attention-deficit hyperactivity disorder (ADHD) model and treated with glucocorticoid receptor (GR) agonist or inhibitor, whereas Wista Kyoto rats (WKY) were chosen as the normal control group. Open-field test and Làt maze test were used to evaluate the spontaneous activities and non-selective attention. The levels of 5-HT in the extracellular fluid specimens of the prefrontal cortex of rats were analyzed by high-performance liquid chromatography. The expressions of GR, 5-HT1A receptor (5-HT1AR), and 5-HT2A receptor (5-HT2AR) in the prefrontal cortex were analyzed through immunohistochemistry.ResultsOur study demonstrated that the 5-HT level was lower in the prefrontal cortex of SHR compared to that of WKY. The Open-field test and Làt maze test showed that GR agonist (dexamethasone, DEX) intervention ameliorated attention deficit and hyperactive behavior, whereas GR inhibitor (RU486) aggravated the disorders. With DEX, the expression levels of 5-HT and 5-HT2AR in the prefrontal cortex of SHR were significantly higher than those in the control group, whereas the expression level of 5-HT1AR was lower. However, the expression levels of 5-HT and 5-HT2AR were significantly decreased after the intervention with RU486, while the expression level of 5-HT1AR increased. Results showed that glucocorticoid was negatively correlated with 5-HT1AR and positively correlated with 5-HT2AR.ConclusionIn the prefrontal cortex of ADHD rats, the down-regulation of 5-HT and 5-HT2AR expressions and the up-regulation of 5-HT1AR, compared with WYK rats, suggested a dysfunctional central 5-HT system in ADHD rats. The GR agonist can upregulate the expression of 5-HT and 5-HT2AR and downregulate the expression of 5-HT1AR in the prefrontal cortex of SHR as well as reduce the hyperactivity and attention deficit behavior in SHR, while the opposite was true for the GR inhibitor. It is suggested that the dysfunction of the 5-HT system in ADHD rats is closely related to glucocorticoid receptor activity.

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Section: Introductionmentioning

confidence: 99%

Disturbed relationship between glucocorticoid receptor and 5-HT1AR/5-HT2AR in ADHD rats: A correlation study

Lin

Huang

et al. 2023

Front. Neurosci.

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“…Apart from this fast feedback control, substantial evidence showed that GCs effects via receptors in the adipocytes produced a slow inhibition of HPA axis activity. A negative relationship between circulating leptin and cortisol in depressed and nondepressed men and women of different weight groups also supported an inhibitory influence of adipocyte-released hormone on the HPA axis (Haleem and Gul 2020).…”

Section: Stress Glucocorticoid and Negative Feedback Control Over Hpa...mentioning

confidence: 87%

“…Considering the role of aversive environmental events, there is substantial evidence that these stressful events activate the hypothalamic-pituitary-adrenal (HPA) axis to increase circulating levels of glucocorticoids (GCs), and a greater sensitivity to this fright and flight response increases risk of depression (Haleem and Gul 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The ACTH binds to melanocortin receptors in the adrenal cortex to enhance synthesis and release of corticosteroid hormones, namely, glucocorticoids and mineralocorticoids, from the adrenal cortex (Herman and others 2003). An overactivity of HPA axis and higher circulating GCs can also modulate brain serotonin (5-hydroxytryptamine; 5-HT) and dependent responses to adaptation to stress and precipitate depression (de Kloet and others 2016; Haleem and Gul 2020; Keller and others 2017).…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoids in the Physiological and Transcriptional Regulation of 5-HT1A Receptor and the Pathogenesis of Depression

Haleem

2020

Neuroscientist

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There is growing increase in the global prevalence of depression, but treatment outcome of this highly disabling disease is not satisfactory. Many patients are not benefitted by the currently prescribed antidepressants—together with this partial remission is very common. Improving treatment strategies and developing better therapeutic agents for treating depression is therefore highly needed. Stress-related epigenetic changes play a critical role in the pathogenesis as well as treatment of depression. Stressful events activate hypothalamic-pituitary-adrenal axis to increase circulating levels of glucocorticoids (GCs), and a greater sensitivity to this fright and flight response increases risk of depression. A role of serotonin (5-hydroxytryptamine; 5-HT) in responses to stress and in the pathogenesis and treatment of depression is well established. Substantial evidence supports a critical role of 5-HT1A receptors in these effects of 5-HT. The present article targets stress-induced higher and sustained increases of GCs and mediated influences on the physiological as well transcriptional regulation of 5-HT1A receptors to evaluate their causal role in the pathogenesis of depression. It is suggested that synthetic compounds with antagonist activity for GC receptors and agonist activity for 5-HT1A receptors may prove better therapeutic agents for treating depression.

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“… 8 Studies suggest a potential relationship between 5-HT, leptin and cortisol. 9 5-HT regulates its endocrine functions through its several receptor types in brain. Administration of 5-HT precursors has shown to influence leptin levels.…”

Section: Introductionmentioning

confidence: 99%

Behavioral, Hormonal, and Serotonergic Responses to Different Restricted Feeding Schedules in Rats

Saeed

Mahmood

Ali

et al. 2022

Int J�Tryptophan�Res

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To determine the effect of long-term restricted feeding schedules on behavior, serotonergic responses, and neuro-endocrine functions, metabolism of serotonin (5-HT) in the striatum, expression of serotonin-1A (5-HT1A) auto-receptor in the raphe nuclei and circulating levels of leptin and corticosterone were determined in female Wistar rats kept on excessive food restriction schedule. Due to a role of dietary deficiency of tryptophan (Trp) in influencing serotonergic neurotransmission, circulating levels of Trp were also determined. Estimations were done in 2 different restricted feeding models: time-restricted feeding (TRF) and diet restricted (DR). TRF animals were given access to food ad libitum only for 2 hours/day. The DR animals were given a small calculated amount of food each day. We found that chronic food restriction for 5 weeks cause a significant decrease in the body weight and produced hyperactivity in both, TRF and DR animals. Levels of Trp were declined in circulation and in the striatum. Similarly, the levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were decreased in the striatum. Also, the expression of 5-HT1A auto-receptor was declined in the raphe nuclei. These changes in 5-HT metabolism and 5-HT1A auto-receptor expression were more profound in DR animals as compare to TRF animals. Similarly, hypoleptinemia and increased corticosterone found in both models was higher in DR animals. Effect of dietary deficiency of Trp in the modulation of striatal 5-HT metabolism and its consequences on circulating leptin and corticosterone are discussed.

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Circulating leptin, cortisol and gender differences associated with anorexia or obesity in depression

Cited by 12 publications

References 43 publications

Disturbed relationship between glucocorticoid receptor and 5-HT1AR/5-HT2AR in ADHD rats: A correlation study

Disturbed relationship between glucocorticoid receptor and 5-HT1AR/5-HT2AR in ADHD rats: A correlation study

Glucocorticoids in the Physiological and Transcriptional Regulation of 5-HT1A Receptor and the Pathogenesis of Depression

Behavioral, Hormonal, and Serotonergic Responses to Different Restricted Feeding Schedules in Rats

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