The influence of the HPG axis on stress response and depressive-like behaviour in a transgenic mouse model of Huntington's disease

Du, Xin; Pang, Terence Y; Mo, Christina; Renoir, Thibault; Wright, Dean; Hannan, Anthony J.

doi:10.1016/j.expneurol.2014.09.009

Cited by 30 publications

(18 citation statements)

References 89 publications

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“…In keeping, Plk2 was increased in WT animals subjected to maternal separation. BACHD rats, in contrast, showed decreased expression that was further decreased after MS, in line with a general aggravation of HD markers upon stress experiences 27 , 28 , 52 . This aggravating effect further suggests greater sensitivity of BACHD rats to stressful experiences agreeing with hyperactivity of the hypothalamic-pituitary-adrenal axis in HD patients 53 .…”

Section: Discussionmentioning

confidence: 56%

Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease

Novati

Hentrich

Wassouf

et al. 2018

Sci Rep

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Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene which results in progressive neurodegeneration in the striatum, cortex, and eventually most brain areas. Despite being a monogenic disorder, environmental factors influence HD characteristics. Both human and mouse studies suggest that mutant HTT (mHTT) leads to gene expression changes that harbor potential to be modulated by the environment. Yet, the underlying mechanisms integrating environmental cues into the gene regulatory program have remained largely unclear. To better understand gene-environment interactions in the context of mHTT, we employed RNA-seq to examine effects of maternal separation (MS) and environmental enrichment (EE) on striatal gene expression during development of BACHD rats. We integrated our results with striatal consensus modules defined on HTT-CAG length and age-dependent co-expression gene networks to relate the environmental factors with disease progression. While mHTT was the main determinant of expression changes, both MS and EE were capable of modulating these disturbances, resulting in distinctive and in several cases opposing effects of MS and EE on consensus modules. This bivalent response to maternal separation and environmental enrichment may aid in explaining their distinct effects observed on disease phenotypes in animal models of HD and related neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 56%

Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease

Novati

Hentrich

Wassouf

et al. 2018

Sci Rep

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“…puberty, pregnancy, menopause), and thus, may play an important role in the neurocircuitry mediating the interactions between stress, estrogen, and fear. Both the HPA and HPG axes are influenced by similar factors such as trauma, and dysregulation in either system can lead to disturbances in emotional health, and in turn, learning and memory deficits (Dismukes, Johnson, Vitacco, Iturri, & Shirtcliff, 2014; Du et al, 2014; Toufexis et al, 2014). Given this relationship, crosstalk between the HPA and HPG circuitry may be critical to understanding the greater vulnerability to stress and anxiety disorders during the different hormonal phases across the female lifespan (Fig.…”

Section: Gonadal Hormones Stress and Fear Extinctionmentioning

confidence: 99%

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

Maeng

Milad

2015

Hormones and Behavior

299

199

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Women are more vulnerable to stress- and fear-based disorders, such as anxiety and post-traumatic stress disorder. Despite the growing literature on this topic, the neural basis of these sex differences remains unclear, and the findings appear inconsistent. The neurobiological mechanisms of fear and stress in learning and memory processes have been extensively studied, and the crosstalk between these systems is beginning to explain the disproportionate incidence and differences in symptomatology and remission within these psychopathologies. In this review, we discuss the intersect between stress and fear mechanisms and their modulation by gonadal hormones and discuss the relevance of this information to sex differences in anxiety and fear-based disorders. Understanding these converging influences is imperative to the development of more effective, individualized treatments that take sex and hormones into account.

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“…This is especially pertinent as the hypothalamus also regulates the hypothalamic–pituitary–gonadal (HPG) axis, which has been shown to be dysregulated in HD patients ( 383 , 423 , 424 ) and rodent models ( 424 – 426 ). Recently, we reported that despite no changes to estrogen receptor expression in the hypothalamus, an acute injection of the estrogen receptor-β agonist diarylpropionitrile was sufficient to ameliorate the depression-like behavior of female R6/1 HD mice ( 427 ), suggesting that treatments based on modulation of estrogen signaling may prove to be fruitful.…”

Section: Depression In Hdmentioning

confidence: 99%

Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?

2015

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There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD). These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic–pituitary–adrenal (HPA)-axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioral deficits and/or mood disorders. Dysregulation of the HPA-axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, antidepressant drugs, such as the selective serotonin reuptake inhibitors have been shown to alter HPA-axis activity. In this review, we will summarize the current state of knowledge regarding HPA-axis pathology in Alzheimer’s, PD and HD, differentiating between prodromal and later stages of disease progression when evidence is available. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the preclinical evidence to better inform prospective, intervention studies.

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The influence of the HPG axis on stress response and depressive-like behaviour in a transgenic mouse model of Huntington's disease

Cited by 30 publications

References 89 publications

Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease

Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?

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