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Evaluation of Biochemical and Epigenetic Measures of Peripheral Brain-Derived Neurotrophic Factor (BDNF) as a Biomarker in Huntington’s Disease Patients

March 7, 2020 by IISBR

Background: Huntington’s disease (HD) is an autosomal-dominant neurodegenerative movement disorder that presents with prominent cognitive and psychiatric dysfunction. Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of HD, as well as other neurodegenerative and psychiatric disorders, and epigenetic alterations in the complex BDNF promoter have been associated with its deregulation in pathological conditions. BDNF has gained increased attention as a potential biomarker of disease; but currently, the conflicting results from measurements of BDNF in different biofluids difficult the assessment of its utility as a biomarker for HD. Here, we measured BDNF protein levels in plasma (n = 85) and saliva (n = 81) samples from premanifest and manifest HD patients and normal controls using ELISA assays. We further examined DNA methylation levels of BDNF promoter IV using DNA derived from whole blood of HD patients and healthy controls (n = 40) using pyrosequencing. BDNF protein levels were not significantly different in plasma samples across diagnostic groups. Plasma BDNF was significantly correlated with age in control subjects but not in HD patients, nor were significant gender effects observed. Similar to plasma, salivary BDNF was correlated with age only in control subjects, with no gender effects observed. Importantly, we detected significantly lower levels of salivary BDNF in premanifest and manifest HD patients compared to control subjects, with lower BDNF levels being observed in premanifest patients within a predicted 10 years to disease onset. Salivary and plasma BDNF levels were not significantly correlated with one another, suggesting different origins. DNA methylation at four out of the 12 CpG sites studied in promoter IV were significantly altered in HD patients in comparison to controls. Interestingly, methylation at three of these CpG sites was inversely correlated to the Hospital Anxiety and Depression Scale (HADS) scores. BDNF promoter methylation was not correlated with motor or cognitive scores in HD patients, and was not associated with sex or age in neither disease nor control groups. Conclusion: Our studies show that BDNF protein levels are decreased in saliva; and BDNF promoter methylation increased in blood in HD subjects when compared to controls. These findings suggest that salivary BDNF measures may represent an early marker of disease onset and DNA methylation at the BDNF promoter IV, could represent a biomarker of psychiatric symptoms in HD patients.

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Tagged With: bdnf, biochemical measures, Biomarkers, brain-derived neeurotrophic factor, huntington's disease

Use of Pathogen-Specific Antibody Biomarkers to Estimate Waterborne Infections in Population-Based Settings

August 6, 2016 by IISBR

Background: There is increasing interest in the mechanisms and biomarkers through which physical activity influence health across the lifespan. Studies that require phlebotomy are challenging for investigations involving children. Not surprisingly, there is growing interest in the use of saliva in pediatrics for exercise-related biomarker discovery. Very little is known about the relationship of key potential salivary biomarkers (SaBs) and exercise during childhood.

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Tagged With: Antibodies, Biomarkers, Immunoconversion, Pathogens, saliva, Serology, Waterborne infections

Salivary Biomarkers in Response to an Acute Bout of Exercise Before and After Training Program: Poster

July 26, 2016 by IISBR

Background: There is increasing interest in the mechanisms and biomarkers through which physical activity influence health across the lifespan. Studies that require phlebotomy are challenging for investigations involving children. Not surprisingly, there is growing interest in the use of saliva in pediatrics for exercise-related biomarker discovery. Very little is known about the relationship of key potential salivary biomarkers (SaBs) and exercise during childhood.

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Tagged With: Biomarkers, childhood, exercise, saliva, training

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Recent Publications

  • Kimonis, E. R., et al. (2018). Dehydroepiandrosterone (DHEA) and its ratio to cortisol moderate associations between maltreatment and psychopathology in male juvenile offenders. Psychoneuroendocrinology.
  • Gatzke-Kopp, L. M., et al. (2018). Magnitude and Chronicity of Environmental Smoke Exposure Across Infancy and Early Childhood in a Sample of Low-Income Children. Nicotine Tob Res.
  • Pisanic, N., et al. (2018). Minimally Invasive Saliva Testing to Monitor Norovirus Infection in Community Settings. J Infect Dis.
  • Affifi, T. D., et al. (2018). Testing the theory of resilience and relational load (TRRL) in families with type I diabetes. Health Commun.
  • Wheelock, M.D., et al. (2018). Psychosocial stress reactivity is associated with decreased whole brain network efficiency and increased amygdala centrality. Behav Neurosci.
  • Kornienko, O., et al. (2018). Associations Between Secretory Immunoglobulin A and Social Network Structure. Int J Behav Med.
  • Kuhlman, K. R., et al. (2018). Interparental conflict and child HPA-axis responses to acute stress: Insights using intensive repeated measures. J Fam Psychol.
  • Kuhlman, K. R., et al. (2018). HPA-Axis Activation as a Key Moderator of Childhood Trauma Exposure and Adolescent Mental Health. Journal of abnormal child psychology.
  • Corey-Bloom, J., et al. (2018). Salivary levels of total huntingtin are elevated in Huntington’s disease patients. Sci Rep.
  • Martinez, A. D., et al. (2018). Household fear of deportation in Mexican-origin families: Relation to body mass index percentiles and salivary uric acid. Am J Hum Biol.
  • Lucas, T., et al. (2018). Justice for all? Beliefs about justice for self and others and telomere length in African Americans. Cultur Divers Ethnic Minor Psychol.
  • Woerner, J., et al. (2018). Salivary uric acid: Associations with resting and reactive blood pressure response to social evaluative stress in healthy African Americans. Psychoneuroendocrinology.
  • Riis J.L., et al. (2018). The validity, stability, and utility of measuring uric acid in saliva. Biomark Med.

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