Behavioral and serotonergic consequences of decreasing or increasing hippocampus brain-derived neurotrophic factor protein levels in mice

Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders

“…BDNF heterozygotes were also found to have decreased serotonin outflow after treatment with various SSRIs, again suggesting that BDNF is involved in the action of SSRIs (Deltheil et al, 2008b). Investigators further showed that this impact of BDNF on 5HT function is region-specific, indicating that BDNF heterozygous mice display blunted 5HT outflow in ventral hippocampus after treatment with SSRIs (Deltheil et al, 2008a). These data suggest that BDNF may serve to provide functional modulation of the serotonergic system at the level of both the receptor and the transporter.…”

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

“…Divergent 5-HT and GABA Gene Expression Changes Following BDNF Loss from Promoters I and II vs IV and VI BDNF deficiencies are strongly associated with misregulation of both 5-HT and GABA signaling pathways (Deltheil et al, 2008;Guilloux et al, 2012;Hong et al, 2008;Lyons et al, 1999;Rios et al, 2006;Sakata et al, 2009;Tripp et al, 2012). The 5-HT neurochemical signaling system has been consistently associated with control of aggressive behavior (Takahashi et al, 2011).…”

“…Mice engineered to disrupt BDNF signaling display several phenotypes, including hyperphagia-induced obesity, enhanced aggression, changes in cognitive behavior, and blunted response to antidepressant treatments (Autry et al, 2011;Chan et al, 2006;Ito et al, 2011;Lyons et al, 1999;Monteggia et al, 2004;Monteggia et al, 2007;Sakata et al, 2013). In line with BDNF's ability to influence multiple pathways, markers of 5-HT signaling as well as GABAergic transmission are altered in these models (Deltheil et al, 2008;Guilloux et al, 2012;Homberg et al, 2014;Hong et al, 2008;Huang et al, 1999;Luellen et al, 2007;Martinowich and Lu, 2008;Rios et al, 2006;Sakata et al, 2009;Tripp et al, 2012). Consistent with data from manipulation of Bdnf in rodents, BDNF disruption in humans is associated with psychiatric manifestations and neurobehavioral alterations, including obesity and enhanced aggression (Ernst et al, 2012;Han et al, 2008).…”

Positive association between MET allele (BDNF Val66Met polymorphism) and obsessive-compulsive disorder

“…[1][2][3] Neurochemical and behavioral analysis have revealed that a partial impairment in BDNF expression causes physiological disturbances in central serotonergic neurons in early adulthood, eventually leading to the structural deterioration of such neurons in advanced age. Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric condition.…”

“…The Met allele of the BDNF Val66Met polymorphism is associated with reduced BDNF activity and harm avoidance, and it has been suggested that it may be associated with depression, schizophrenia, bipolar disorder and OCD, although findings have been inconsistent. [1][2][3] We sought to investigate this association in a sample of 127 Caucasian patients with OCD born in Brazil and 127 matched healthy controls. The study was approved by the Ethics Committee of the Hospital das Clínicas of the Universidade Federal de Minas Gerais and all participants were required to sign informed consent forms.…”