The Role of the Amygdala in Regulating the Hypothalamic-Pituitary-Adrenal Axis

Weidenfeld, Joseph; Ovadia, Haim

doi:10.5772/67828

Cited by 12 publications

(14 citation statements)

References 50 publications

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“…Our results also complement previous reports of dissociations between anxiety endophenotypes (Blaser and Rosemberg, 2012;Bai et al, 2016;van den Bos et al, 2017;Golla et al, 2020). The relationship between stress and feeding has been established in humans, rodents and zebrafish (Born et al, 2010;Rudenga et al, 2013;De Marco et al, 2014;Weidenfeld and Ovadia, 2017). Stress results in appetite dysregulation, causing stress-induced anorexia or in other cases, excessive caloric intake.…”

Section: Discussionsupporting

confidence: 90%

Osmotic Stress Uncovers Correlations and Dissociations Between Larval Zebrafish Anxiety Endophenotypes

Cheng

Tan²,

Chua³

et al. 2022

Front. Mol. Neurosci.

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Larval zebrafish are often used to model anxiety disorders. However, since it is impossible to recapitulate the full complexity and heterogeneity of anxiety in this model, examining component endophenotypes is key to dissecting the mechanisms underlying anxiety. While individual anxiety endophenotypes have been examined in zebrafish, an understanding of the relationships between them is still lacking. Here, we investigate the effects of osmotic stress on a range of anxiety endophenotypes such as thigmotaxis, dark avoidance, light-dark transitions, sleep, night startle, and locomotion. We also report a novel assay for stress-induced anorexia that extends and improves on previously reported food intake quantification methods. We show that acute <30 min osmotic stress decreases feeding but has no effect on dark avoidance. Further, acute osmotic stress dose-dependently increases thigmotaxis and freezing in a light/dark choice condition, but not uniform light environmental context. Prolonged >2 h osmotic stress has similar suppressive effects on feeding while also significantly increasing dark avoidance and sleep, with weaker effects on thigmotaxis and freezing. Notably, the correlations between anxiety endophenotypes were dependent on both salt and dark exposure, with increased dissociations at higher stressor intensities. Our results demonstrate context-dependent effects of osmotic stress on diverse anxiety endophenotypes, and highlight the importance of examining multiple endophenotypes in order to gain a more complete understanding of anxiety mechanisms.

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Section: Discussionsupporting

confidence: 90%

Osmotic Stress Uncovers Correlations and Dissociations Between Larval Zebrafish Anxiety Endophenotypes

Cheng

Tan²,

Chua³

et al. 2022

Front. Mol. Neurosci.

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“…Evidence from cellular to human studies indicates that pain and stress activate the HPA axis. The amygdala and hippocampus may play important yet distinct roles in the HPA axis (Smith and Vale, 2006 ; Weidenfeld and Ovadia, 2017 ). BDNF also substantially participates in the regulation of HPA axis activity (Naert et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity

Low

Kuo

Tsai³

et al. 2018

Front. Neurosci.

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The irregularity and uncertainty of neurophysiologic signals across different time scales can be regarded as neural complexity, which is related to the adaptability of the nervous system and the information processing between neurons. We recently reported general loss of brain complexity, as measured by multiscale sample entropy (MSE), at pain-related regions in females with primary dysmenorrhea (PDM). However, it is unclear whether this loss of brain complexity is associated with inter-subject genetic variations. Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin in the brain and is crucial to neural plasticity. The BDNF Val66Met single-nucleotide polymorphism (SNP) is associated with mood, stress, and pain conditions. Therefore, we aimed to examine the interactions of BDNF Val66Met polymorphism and long-term menstrual pain experience on brain complexity. We genotyped BDNF Val66Met SNP in 80 PDM females (20 Val/Val, 31 Val/Met, 29 Met/Met) and 76 healthy female controls (25 Val/Val, 36 Val/Met, 15 Met/Met). MSE analysis was applied to neural source activity estimated from resting-state magnetoencephalography (MEG) signals during pain-free state. We found that brain complexity alterations were associated with the interactions of BDNF Val66Met polymorphism and menstrual pain experience. In healthy female controls, Met carriers (Val/Met and Met/Met) demonstrated lower brain complexity than Val/Val homozygotes in extensive brain regions, suggesting a possible protective role of Val/Val homozygosity in brain complexity. However, after experiencing long-term menstrual pain, the complexity differences between different genotypes in healthy controls were greatly diminished in PDM females, especially in the limbic system, including the hippocampus and amygdala. Our results suggest that pain experience preponderantly affects the effect of BDNF Val66Met polymorphism on brain complexity. The results of the present study also highlight the potential utilization of resting-state brain complexity for the development of new therapeutic strategies in patients with chronic pain.

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“…Appetite, or the drive to consume food, is often dysregulated in mood and anxiety disorders, as observed behaviorally and supported by numerous studies (Rudenga et al, 2013;Weidenfeld and Ovadia, 2017). Feeding when stressed is correlated with reduced activation in reward areas of the brain (amygdala, hippocampus, and cingulate cortex), suggesting that stress causes reduced sensitivity to the pleasurable rewards derived from food, which leads to excessive eating (Born et al, 2010).…”

Section: Appetite Dysregulationmentioning

confidence: 93%

Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health

Tan

Ang

Wee

2022

Front. Mol. Neurosci.

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Animal models are essential for the discovery of mechanisms and treatments for neuropsychiatric disorders. However, complex mental health disorders such as depression and anxiety are difficult to fully recapitulate in these models. Borrowing from the field of psychiatric genetics, we reiterate the framework of ‘endophenotypes’ – biological or behavioral markers with cellular, molecular or genetic underpinnings – to reduce complex disorders into measurable behaviors that can be compared across organisms. Zebrafish are popular disease models due to the conserved genetic, physiological and anatomical pathways between zebrafish and humans. Adult zebrafish, which display more sophisticated behaviors and cognition, have long been used to model psychiatric disorders. However, larvae (up to 1 month old) are more numerous and also optically transparent, and hence are particularly suited for high-throughput screening and brain-wide neural circuit imaging. A number of behavioral assays have been developed to quantify neuropsychiatric phenomena in larval zebrafish. Here, we will review these assays and the current knowledge regarding the underlying mechanisms of their behavioral readouts. We will also discuss the existing evidence linking larval zebrafish behavior to specific human behavioral traits and how the endophenotype framework can be applied. Importantly, many of the endophenotypes we review do not solely define a diseased state but could manifest as a spectrum across the general population. As such, we make the case for larval zebrafish as a promising model for extending our understanding of population mental health, and for identifying novel therapeutics and interventions with broad impact.

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The Role of the Amygdala in Regulating the Hypothalamic-Pituitary-Adrenal Axis

Cited by 12 publications

References 50 publications

Osmotic Stress Uncovers Correlations and Dissociations Between Larval Zebrafish Anxiety Endophenotypes

Osmotic Stress Uncovers Correlations and Dissociations Between Larval Zebrafish Anxiety Endophenotypes

Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity

Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health

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