Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain–liver axis

Abstract

Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF and BDNF pro-peptide in the parietal cortex, cerebellum, liver and spleen from control, major depressive disorder (MDD), schizophrenia (SZ) and bipolar disorder (BD) groups. The levels of mature BDNF in the parietal cortex from MDD, SZ and BD groups were significantly lower than the control group, whereas the levels of BDNF pro-peptide in this area were significantly higher than controls. In contrast, the levels of proBDNF and BDNF pro-peptide in the cerebellum of MDD, SZ and BD groups were significantly lower than controls. Moreover, the levels of mature BDNF from the livers of MDD, SZ and BD groups were significantly higher than the control group. The levels of mature BDNF in the spleen did not differ among the four groups. Interestingly, there was a negative correlation between mature BDNF in the parietal cortex and mature BDNF in the liver in all the subjects. These findings suggest that abnormalities in the production of mature BDNF and BDNF pro-peptide in the brain and liver might have a role in the pathophysiology of psychiatric disorders, indicating a brain–liver axis in psychiatric disorders.

Brain-derived neurotrophic factor-TrkB signaling in the medial prefrontal cortex plays a role in the anhedonia-like phenotype after spared nerve injury

“…In addition, we also found both SNI rats with or without anhedonia-like phenotypes have lower tissue levels of BDNF in the muscle and liver compared with those in sham-operated rats. Interestingly, we observed alterations in BDNF-TrkB signaling in the liver from mood disorders including major depressive disorder and bipolar disorder, suggesting a possible role of BDNF-TrkB signaling in mood disorders [47]. Given the key role of BDNF-TrkB signaling in psychiatric disorders [48,49], it is likely that alterations in BDNF-TrkB signaling may contribute to anhedonia susceptibility to SNI surgery.…”

Associations between Serum Brain-Derived Neurotrophic Factors and Bipolar Disorder

“…The participants were sorted Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the central nervous system (CNS), plays an important role in neurogenesis, neuronal survival, and synaptic plasticity [5,6]. BDNF levels measures in blood could reflect illness activity in the brain due to a positive correlation of BDNF levels between blood and cortex in mice, rats and pigs [7].…”

“…In addition, the tropomyosin receptor kinase (TrkB), a receptor of BDNF on cell membrane, is involved in bipolar disorder [8,9]. Several studies have adopted the BDNF as a molecular candidate for developing bipolar disorder [6,10]. Recent studies had demonstrated that BDNF levels are lower in patients during active phases than BDNF levels in healthy controls [10][11][12][13][14].…”

Emerging and evolving concepts in the pathobiology and treatment of psychosis

“…24,25 In this context, Kingston and colleagues 26 and antipsychotic drug action. 30,31 In conclusion, we hope that this Special Issue illuminates (i) important aspects of evolving concepts of schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder with psychotic features, and (ii) how these aspects are increasingly complemented by yet more heuristic emerging concepts of psychotic ideation, psychotic illness, and pathobiology across conventional diagnostic boundaries within a milieu of psychosis. Such juxtaposition refreshes the field and increases the likelihood of progress.…”

“…Liu and colleagues investigate the effects of Hcyb1, a novel inhibitor of phosphodiesterase2A (PDE2A), in 2 contexts: as a putative antidepressant agent and as a neuroprotective agent in terms of increasing cell viability/promoting neuronal proliferation. They report Hcyb1 to exert both antidepressant‐like effects in behavioral models and neuroprotective effects in cell lines that are likely mediated by cAMP/cGMP‐CREB‐BDNF signaling, disruption of which has been implicated both in depression and psychosis and in antidepressant and antipsychotic drug action …”