BDNF and Schizophrenia: From Neurodevelopment to Neuronal Plasticity, Learning, and Memory

Abstract

Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been related not only to neurodevelopment and neuroprotection, but also to synapse regulation, learning, and memory. Research focused on the neurobiology of schizophrenia has emphasized the relevance of neurodevelopmental and neurotoxicity-related elements in the pathogenesis of this disease. Research focused on the clinical features of schizophrenia in the past decades has emphasized the relevance of cognitive deficits of this illness, considered a core manifestation and an important predictor for functional outcome. Variations in neurotrophins such as BDNF may have a role as part of the molecular mechanisms underlying these processes, from the neurodevelopmental alterations to the molecular mechanisms of cognitive dysfunction in schizophrenia patients.

Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury

“…Variables included in the models (age, gender, race, blood pressure, history of hypertension, history of depression or schizophrenia) [34][35][36][37] were selected based on an a priori literature …”

Envolvimento Da Flora Intestinal Na Modulação De Doenças Psiquiátricas

“…Os fatores etiológicos incluem o envolvimento de fatores genéticos e ambientais. Muitos pacientes esquizofrênicos também apresentam distúrbios gastrointestinais, evidenciando um possível envolvimento da composição da microbiota intestinal na patofisiologia da doença (146)(147)(148). Além disso, vários estudos têm demonstrado que o sistema imunológico está desregulado em pacientes esquizofrênicos, além de haver uma correlação entre o risco de desenvolver esquizofrenia e genes relacionados com o sistema imunológico (149)(150)(151)(152)(153), sugerindo uma possível modulação da flora intestinal.…”

Intronic miRNA miR-3666 Modulates its Host Gene FOXP2 Functions in Neurodevelopment and May Contribute to Pathogenesis of Neurological Disorders Schizophrenia and Autism

“…We assume the upregulation of FOXP2 may be responsible for low BDNF levels; FOXP2 and miR-3666 may indirectly repress BDNF by inhibition of CREB1. In the BDNF expression profile, one sample shows much higher expression level compared to the rest, which may be due to age-related differences or the use of anti-psychotic drugs [88,91,92]. Moreover, FOXP2 probably directly inhibit DISC1 (Disrupted-In-Schizophrenia 1) [93], whereas miR-3666 may indirectly inhibit it by repressing NDEL1 and hence disrupting DISC1-NDEL1 interaction [63].…”

“…As model 3 (Figure 5c) shows, the candidate gene ERBB4 [87], being a common target gene, may be directly regulated by miR-3666 and FOXP2. However, miR-3666 and FOXP2 can regulate the levels of candidate genes BDNF (Brain-Derived Neurotrophic Factor) [88], DGCR2 (DiGeorge syndrome critical region gene 2) [89], NRG1 [60] through common target CREB1. This relation is evident from the GEO2R analysis of GSE17612 [90] expression data where upregulation of FOXP2 The left circle represents disease candidate genes, where the number in the blue circle corresponds to genes exclusive for the disease.…”