Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder

Abstract

Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins-as crucial moderators of neuroplasticity-impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = -2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η (2) = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.

Serotonin dysregulation in Fragile X Syndrome: implications for treatment

“…Serum levels of BDNF mRNA and BDNF protein are overall lower in patients with autism (49) and serum BDNF mRNA levels may positively correlate with IQ in patients with ASD (49). A crucial experiment by Lauterborn et al (44) showed that impaired LTP (long term potentiation) in the Fmr1-KO mouse model is rescued when hippocampal slices are bathed in BDNF.…”

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

“…Contradictory evidences support an association between BDNF expression and ASD [25][26][27][29][30][31][32]. Recently, peripheral mRNA expression of BDNF was analysed also in the whole blood searching for possible biologic markers for ASD [32].…”

“…Nevertheless, other authors reported decreased BDNF and NT3 levels in serum of autistic patients [30,31]. Regarding messenger RNA (mRNA) levels, more recent studies revealed a significant reduction in BDNF expression [32]. The diversity of hitherto existing results might be due to varying patient groups included, differences in analysed tissues and utilized methods as well as influences of cofactors such as age and puberty state [32].…”

“…Regarding messenger RNA (mRNA) levels, more recent studies revealed a significant reduction in BDNF expression [32]. The diversity of hitherto existing results might be due to varying patient groups included, differences in analysed tissues and utilized methods as well as influences of cofactors such as age and puberty state [32]. Peripheral expression analyses and molecular biomarker approaches, such as those described, finally aim at the knowledge of specific blood expression profiles for an early diagnosis of ASD and early beginning of specific therapeutic interventions.…”

7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders

“…Studies have found reduced peripheral BDNF protein and mRNA levels in the blood of neonates (Abdallah et al, 2013), children, adolescents (Katoh-Semba et al, 2007;Taurines et al, 2014) and adults with ASDs (Hashimoto et al, 2006). In particular, KatohSemba and colleagues found when examining the early developmental profile of BDNF expression that in healthy controls, serum BDNF protein level increase over the first few years of development before plateauing at adulthood whereas in autism sufferers BDNF levels were significantly lower from the ages 0e9 years compared to teenage and adult patients as well as controls, strongly indicative of a delayed BDNF developmental trajectory (Katoh-Semba et al, 2007).…”