BDNF transcripts modulation in the blood of subjects exposed to childhood trauma history

Adverse influences, particularly early in development, can result in permanent changes in physiology and metabolism, which result in increased disease risk in adulthood. Childhood trauma experiences have been indeed found able to modulate brain structure and functions through alterations in neuroplasticity [1]. Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin that plays a crucial role in neuronal development and plasticity; it is involved in the effects of stress and also in the pathogenesis of several mental disorders. The human BDNF gene is very complex and it consists of several transcripts that are all characterized by the presence of the common coding exon at the 3’end [2,3]. To date no information regarding the expression of BDNF transcripts in the blood and of their possible modulation by stressful experiences is available. The aim of this study was to characterize the expression of BDNF transcripts in the blood of human subjects and investigate their modulation in association to exposure to stressful life experiences. We have measured total BDNF mRNA levels through Real Time PCR in peripheral blood of adult subjects (n=40) clinically assessed for exposure during childhood to sexual, emotional and/or physical trauma by childhood trauma questionnaire. We found a significant reduction in the mRNA levels of total BDNF in the blood of subjects exposed to childhood trauma versus not exposed subjects (p<0.05, −32%). Then, to identify the BDNF transcript able to contribute to this BDNF modulation, we assessed the expression levels of the different BDNF transcript in the blood and we found that only transcripts IV and IX were well expressed. Thus, we focused our subsequent analyses on these transcripts and we evaluated by Real Time PCR their modulation in association with childhood trauma events. We found a significant modulation of both the transcripts, although a more pronounced effect was observed for transcript IV (−71%, p<0.05 for transcript IV; −35%, p<0.05 for transcript IX). Share Like 0 Tweet. In order to better characterize BDNF variants modulation we measured the levels of total BDNF and of the transcript IV and IX in an in vitro model represented by human hippocampal progenitors stem cells (HPSc) that we treated for three days during proliferation phase. Gene expression analyses were performed after 10 days of differentiation. We found that BDNF total levels and transcript IV and IX were downregulated also in HPC treated with cortisol (total BDNF −25%, p<0.05; transcript IV −19%, p<0.05; transcript IX −27%, p<0.05). In order to investigate the molecular mechanisms underlying these long lasting changes in BDNF we are evaluating the role of DNA methylation and miRNAs as possible epigenetic mechanisms. These data indicate that BDNF levels are reduced in the peripheral blood of subjects exposed to childhood trauma and that similar modulation occurs in neurons. BDNF variants IV and IX are the transcripts that contribute to BDNF modulation and a better characterization of their modulation may identify novel target for preventative therapies in subjects exposed to trauma and thus at higher risk to develop psychiatric illnesses in adulthood.