Dataset Information

BDNF mRNA Expression in Leukocytes and Frontal Cortex Function in Drug Use Disorder.

ABSTRACT: The brain-derived neurotrophic factor (BDNF) is a neurotrophin recognized to play a major role in neuroplastic modifications associated to drug abuse, being involved in various behavioral changes found in drug use disorders, such as drug sensitization, craving and relapses. These neuroplastic changes were shown to affect the prefrontal cortex functions, which can be briefly measured through cognitive tests such as the Frontal Assessment Battery (FAB). In this study we investigated the BDNF mRNA expression in peripheral blood lymphocytes of crack-cocaine use disorder (CUD) and alcohol use disorder (AUD) patients, after drug detoxification treatment, using a real-time PCR approach and examining its association to FAB performance. BDNF mRNA expression was found to be higher by 2.25-fold in CUD patients and by 2-fold in the AUD patients when normalized to controls, and these values were found to be associated with FAB scores. This preliminary study evaluates, for the first time, BDNF mRNA expression in leukocytes and its relationship to FAB scores in crack-cocaine and alcohol use disorder patients.

SUBMITTER: Anders QS

PROVIDER: S-EPMC7248396 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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BDNF mRNA Expression in Leukocytes and Frontal Cortex Function in Drug Use Disorder.

Anders Quézia Silva QS Ferreira Leonardo Villaverde Buback LVB Rodrigues Livia Carla de Melo LCM Nakamura-Palacios Ester Miyuki EM

Frontiers in psychiatry 20200519

The brain-derived neurotrophic factor (BDNF) is a neurotrophin recognized to play a major role in neuroplastic modifications associated to drug abuse, being involved in various behavioral changes found in drug use disorders, such as drug sensitization, craving and relapses. These neuroplastic changes were shown to affect the prefrontal cortex functions, which can be briefly measured through cognitive tests such as the Frontal Assessment Battery (FAB). In this study we investigated the BDNF mRNA ...[more]

PMID: 32508693

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Project description:Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD (n = 20), iCJD (n = 11), sCJD (n = 23), gPrD (n = 30), and AD (n = 14) patients and age-matched controls (n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin dysregulation found in prion and non-prion neurodegenerative disorders. In addition, these results suggest that gene expression of HBB and HBA1/2 in brain tissue is differentially affected by distinct prion and prion-like aggregating protein strains. Validation of these results in more accessible tissues could prompt the development of novel diagnostic tests for neurodegenerative disorders.

Dataset Information

BDNF mRNA Expression in Leukocytes and Frontal Cortex Function in Drug Use Disorder.

Publications

BDNF mRNA Expression in Leukocytes and Frontal Cortex Function in Drug Use Disorder.

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