BDNF^+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders

Abstract

Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain‐derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF+/−) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF+/− rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety‐like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted‐in‐schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN+/− rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive‐like symptoms.

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

“…Indeed, cognitive ability including mood is largely dependent on BDNF, a neurotrophin playing a crucial role in neuroplasticity and neurogenesis (14). In agreement with this, BDNF +/− rats exhibited anhedonia and anxiety-like behaviour (15) and the Val66Met polymorphism that results in abnormal BDNF signalling (16) increased the risk of mental diseases (17,18). It is noteworthy that brain BDNF levels are decreased in diseases associated with ED (19,20) or after immune challenge (21).…”

PPARγ and Cognitive Performance

“…There is much evidence in literature describing a significant reduction in peripheral BDNF [149,150] concentrations in patients with schizophrenia. Very recently, Martis et al [151] have shown that mice with BDNF deficiency exhibit a depressive phenotype. Previously, Wysokinsky et al [152] observed a peripheral reduction in BDNF level in patients with schizophrenia with depressive symptoms.…”

Association Between Depressive Symptoms and Serum Brain-Derived Neurotrophic Factor Levels in Patients With First-Episode and Drug-Naïve Schizophrenia

“…In addition to schizophrenia, altered levels of BDNF in the hippocampus and blood have been associated with other psychiatric disorders, including depression ( 19 , 20 ). For example, several animal studies have shown that BDNF appears to have a crucial role in depressive-like behavior in rats ( 21 , 22 ). In human research, the description of BDNF levels in peripheral blood may be traced back to the early work of Karege, who suggested that major depression was characterized by low serum BDNF levels ( 23 ).…”