Abstract
BDNF plays a pivotal role in neuroplasticity events, vulnerability and resilience to stress-related disorders, being decreased in depressive patients and increased after antidepressant treatment. BDNF was found to be reduced in patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT−/−) is one of the animal models used to investigate the underlying molecular mechanisms of depression in humans. They present decreased BDNF levels, and anxiety- and depression-like behavior. To investigate whether upregulating BDNF would ameliorate the phenotype of SERT−/− rats, we overexpressed BDNF locally into the ventral hippocampus and submitted the animals to behavioral testing. The results showed that BDNF overexpression in the vHIP of SERT−/− rats promoted higher sucrose preference and sucrose intake; on the first day of the sucrose consumption test it decreased immobility time in the forced swim test and increased the time spent in the center of a novel environment. Furthermore, BDNF overexpression altered social behavior in SERT−/− rats, which presented increased passive contact with test partner and decreased solitary behavior. Finally, it promoted decrease in plasma corticosterone levels 60 min after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT−/− rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential target to new therapeutic approaches to improve depressive symptoms.
Highlights
An essential part of our daily performance has to do with our capability to adjust and respond to unforeseen events
Lentivirus Transfection Leads to brain-derived neurotrophic factor (BDNF) Overexpression in Ventral Hippocampus of serotonin reuptake transporter (SERT)+/+
It has been hypothesized that the intricate system regulating the BDNF gene results in the generation of BDNF transcripts that create a spatial code for BDNF gene expression throughout the brain [60]
Summary
An essential part of our daily performance has to do with our capability to adjust and respond to unforeseen events. Adaptation to unexpected environmental changes relies on our ability to develop resilience and display behavioral flexibility. This flexibility is a result of several mechanisms occurring in the brain that are generally called plasticity. Brain plasticity or neuroplasticity can be defined as the adjustments the nervous system undergoes in response to diverse stimuli to achieve reorganization at the structural, functional or cellular connectivity level [1]. Many molecular networks might be involved in neuroplasticity, including the serotonin and the brain-derived neurotrophic factor (BDNF)
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