Related Experiment Video
Updated: Jun 10, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Hypothalamic-pituitary-adrenal axis functioning in Huntington's disease mutation carriers compared with
Erik van Duijn1, Mischa A Selis, Erik J Giltay
1Department of Psychiatry, Leiden University Medical Center, The Netherlands. e.van_duijn@lumc.nl
Brain Research Bulletin
|August 18, 2010
Summary
Huntington's disease (HD) mutation carriers show altered morning cortisol secretion, specifically a higher cortisol awakening response (CAR), even before motor symptoms appear. This suggests early HPA axis changes in neurodegeneration.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Huntington's disease (HD) involves neurodegeneration across brain regions, including the hypothalamus.
- The hypothalamic-pituitary-adrenal (HPA) axis is a key neuroendocrine system potentially affected in HD.
Purpose of the Study:
- To investigate HPA axis functioning in individuals with and without Huntington's disease mutations.
- To determine if HPA axis disturbances are present before the onset of motor symptoms in HD.
Main Methods:
- Cross-sectional study of 26 presymptomatic HD mutation carriers, 58 symptomatic HD mutation carriers, and 28 controls.
- Assessment of HPA axis function using salivary cortisol measurements: day curve, cortisol awakening response (CAR), area under the curve (AUC), morning rise, and dexamethasone suppression test (DST).
Main Results:
- A statistically significant difference in CAR was observed between the three groups.
- Presymptomatic HD mutation carriers exhibited higher cortisol concentrations at 45 and 60 minutes post-awakening compared to symptomatic carriers and controls.
- No significant differences were found in AUC, evening, or post-DST cortisol concentrations.
Conclusions:
- A mild disturbance in morning cortisol secretion, specifically the CAR, is evident in HD mutation carriers.
- This alteration in HPA axis function precedes the development of motor symptoms in Huntington's disease.
- Findings suggest early neuroendocrine changes associated with neurodegeneration in HD.
More Related Videos
10:52Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
Published on: December 10, 2021
09:37A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Related Concept Videos
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
01:37Hypothalamic-Pituitary Axis
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
01:19Cushing Syndrome II: Pathophysiology
Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
01:26Cushing Syndrome I: Introduction
Cushing syndrome refers to the collection of clinical manifestations that arise when tissues are exposed to excessive amounts of cortisol or cortisol-like medications over an extended period. Cortisol, a glucocorticoid produced by the adrenal cortex, regulates metabolism, immune responses, and the body’s adaptation to stress. When its concentration remains chronically elevated, these physiological pathways become dysregulated, resulting in the characteristic features of the syndrome.Exogenous...
01:27Adrenal Gland Disorders
Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...