scholarly journals The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 498
Author(s):  
Sofia Dionysopoulou ◽  
Evangelia Charmandari ◽  
Alexandra Bargiota ◽  
Nikolaos F Vlahos ◽  
George Mastorakos ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Hpa Axis ◽  
Causal Link ◽  
Healthy Diet ◽  
Hypothalamic Pituitary Adrenal ◽  
Peptide Receptor ◽  
Diet Induced Obesity ◽  
Hypothalamic Inflammation ◽  
Glucagon Like Peptide

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.

scholarly journals Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?

2021 ◽  
Author(s):  
Susanne Fischer ◽  
Tabea Schumacher ◽  
Christine Knaevelsrud ◽  
Ulrike Ehlert ◽  
Sarah Schumacher
Keyword(s):  
Hpa Axis ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Ptsd Symptoms ◽  
Post Traumatic Stress ◽  
Alternative Treatments ◽  
Hypothalamic Pituitary Adrenal ◽  
Post Traumatic

Abstract Background Less than half of all individuals with post-traumatic stress disorder (PTSD) remit spontaneously and a large proportion of those seeking treatment do not respond sufficiently. This suggests that there may be subgroups of individuals who are in need of augmentative or alternative treatments. One of the most frequent pathophysiological findings in PTSD is alterations in the hypothalamic–pituitary–adrenal (HPA) axis, including enhanced negative feedback sensitivity and attenuated peripheral cortisol. Given the role of the HPA axis in cognition, this pattern may contribute to PTSD symptoms and interfere with key processes of standard first-line treatments, such as trauma-focused cognitive behavioural therapy (TF-CBT). Methods This review provides a comprehensive summary of the current state of research regarding the role of HPA axis functioning in PTSD symptoms and treatment. Results Overall, there is preliminary evidence that hypocortisolaemia contributes to symptom manifestation in PTSD; that it predicts non-responses to TF-CBT; and that it is subject to change in parallel with positive treatment trajectories. Moreover, there is evidence that genetic and epigenetic alterations within the genes NR3C1 and FKBP5 are associated with this hypocortisolaemic pattern and that some of these alterations change as symptoms improve over the course of treatment. Conclusions Future research priorities include investigations into the role of the HPA axis in day-to-day symptom variation, the time scale in which biological changes in response to treatment occur, and the effects of sex. Furthermore, before conceiving augmentative or alternative treatments that target the described mechanisms, multilevel studies are warranted.

scholarly journals TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandre Moura-Assis ◽  
Pedro A. S. Nogueira ◽  
Jose C. de-Lima-Junior ◽  
Fernando M. Simabuco ◽  
Joana M. Gaspar ◽  
...  
Keyword(s):  
Dietary Fats ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Hypothalamic Inflammation ◽  
Novel Target ◽  
Tlr4 Activation ◽  
Leucine Rich Repeats ◽  
Body Energy

AbstractObesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalamic inflammation remains unknown. Here, we demonstrate that the knockdown of TLR4-interactor with leucine-rich repeats (Tril), a functional component of TLR4, resulted in reduced hypothalamic inflammation, increased whole-body energy expenditure, improved the systemic glucose tolerance and protection from diet-induced obesity. The POMC-specific knockdown of Tril resulted in decreased body fat, decreased white adipose tissue inflammation and a trend toward increased leptin signaling in POMC neurons. Thus, Tril was identified as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental obesity and its inhibition in the hypothalamus may represent a novel target for obesity treatment.

Headliner in Physiology and Management of Childhood Asthma: Hypothalamic-Pituitary-Adrenal Axis

2020 ◽  
Vol 16 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Nese Akcan ◽  
Nerin N. Bahceciler
Keyword(s):  
Side Effects ◽  
Hpa Axis ◽  
Inhaled Corticosteroids ◽  
Cushing Syndrome ◽  
Early Recognition ◽  
Persistent Asthma ◽  
Receptor Expression ◽  
Hypothalamic Pituitary Adrenal

Asthma is the most common chronic inflammatory disease of children. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy which are the most effective, commonly used treatment of persistent asthma. Mostly, studies on the relationship between asthma and cortisol have focused on side effects of treatment. Recently, asthmatic patients not treated with ICS have been reported to have an attenuated activity and/or responsiveness of their Hypothalamic-Pituitary- Adrenal (HPA) axis. Moreover, it has been proposed that asthma worsening with stress may be due to a dysfunctional HPA axis, or cortisol insensitivity due to chronic psychological stress through impaired glucocorticoid receptor expression or function. Although long-term ICS treatment might produce adrenal suppression or iatrogenic Cushing syndrome, improvement of adrenal function has also been detected in some of asthmatic cases. Thus, the response scheme of HPA axis still contains undiscovered features in asthma. The management of asthma can be improved by increasing knowledge on the role of HPA axis in asthma pathophysiology. The risk for side effects of ICS can be minimized through increased awareness, early recognition of at-risk patients and regular patient follow-up. This review was written to draw attention to the role of HPA axis in both asthma and its treatment and to illustrate a follow up algorithm of HPA axis in the management of asthma.

Neurobiology of Mood Disorders

2018 ◽  
Author(s):  
Genoveva Uzunova ◽  
Vera Nezgovorova ◽  
Danya Schlussel ◽  
Eric Hollander
Keyword(s):  
Synaptic Plasticity ◽  
Transcranial Magnetic Stimulation ◽  
Mood Disorders ◽  
Magnetic Stimulation ◽  
Major Depressive ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Central Nervous Systems ◽  
Pituitary Adrenal Axis

Mood disorders (major depressive disorders [MDDs] and bipolar disorders [BDs]) are common psychiatric conditions and major causes of morbidity and mortality worldwide. Their neurobiology is extensively studied, and major advances have been made in understanding the neuroanatomic, neurochemical, synaptic plasticity, and genetic correlates. In this review, we discuss the major neuroanatomic regions in the brain affected in mood disorders and brain structural and functional alterations, the main hypotheses for the neurobiology, the major neurotransmitters and neuromodulators implicated, the synaptic plasticity changes, the role of stress and the hypothalamic-pituitary-adrenal axis, the importance of circadian rhythms, and the role of genetics. We discuss differences in the neurobiology between MDDs and BDs and connect the knowledge of neurobiology to therapeutics. We discuss the main classes of medications, such as antidepressants for treatment of MDD and mood-stabilizing drugs for treatment of BD, and neuromodulation therapies such as transcranial magnetic stimulation. We point to unanswered questions and future directions, such as elucidation of the role of atypical neurotransmitters in mood disorders, the need for better understanding of the genetics and interactions between the immune and central nervous systems, and the development of biomarkers and personalized therapeutics based on the neurobiology. Notably, there are discrepancies in the current scientific knowledge and many unanswered questions in the neurobiology due to the different ages of patients, disease stage, presence of medications, and other comorbidities. It is notable, however, that mood disorders have a clearly established biological basis with alterations in the immune and central nervous systems that affect synaptic plasticity, neural circuits, and larger-scale brain networks and communicate with the autonomic nervous system. This review contains 5 figures, 4 tables and 62 references Key words: antidepressant, bipolar disorder, epigenetics, hypothalamic-pituitary-adrenal axis, immune system, limbic system, major depressive disorder, mood stabilizer, neurotransmitter, synaptic plasticity, transcranial magnetic stimulation 

Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis

2005 ◽  
Vol 289 (5) ◽  
pp. E857-E863 ◽  
Author(s):  
Anastasia Kariagina ◽  
Svetlana Zonis ◽  
Mahta Afkhami ◽  
Dmitry Romanenko ◽  
Vera Chesnokova
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Leukemia Inhibitory Factor ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Inhibitory Factor ◽  
Mrna Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Protein Levels

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130 family. LIF is induced peripherally and within the brain during inflammatory or chronic autoimmune diseases and is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3 μg/mouse, ip) markedly decreased GR mRNA levels in murine hypothalamus (5-fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within 2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF effects on GR expression. Conversely, mice with LIF deficiency exhibited increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold, respectively; P < 0.01 for both) and increased GR protein expression when compared with wild-type littermates. The suppressive effects of dexamethasone on GR were more pronounced in LIF-null animals. These data suggest that LIF maintains the HPA axis activation by decreasing GR expression and raise the possibility that LIF might contribute to the development of central glucocorticoid resistance during inflammation.

Psychiatric disorders and biological factors

2019 ◽  
pp. 33-44
Author(s):  
Navneet Kapur ◽  
Robert Goldney
Keyword(s):  
Psychiatric Disorders ◽  
Mood Disorders ◽  
Suicidal Behaviour ◽  
Biological Factors ◽  
Hypothalamic Pituitary Adrenal ◽  
Important Interaction ◽  
Increase Risk ◽  
Physical Disorders ◽  
Drug And Alcohol

This chapter discusses the role of psychiatric disorders, biological factors, and genetic factors in suicidal behaviour. These increase risk and the susceptibility of some individuals to react more severely to stress but do not inevitably lead to suicide. All psychiatric disorders are associated with a higher risk of suicide, particularly mood disorders, schizophrenia, and drug and alcohol misuse. Comorbidity (multiple psychiatric disorders at the same time or psychiatric and physical disorders together) is common. The vulnerability to suicidal behaviour is partly inherited. The serotonin and hypothalamic–pituitary–adrenal systems are associated with suicide; however biological factors lack specificity. There is an important interaction between genetic susceptibility and the environment—stressors may have more of an impact in individuals who carry particular genes.

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