Role of proBDNF and BDNF in dendritic spine plasticity and depressive-like behaviors induced by an animal model of depression

Abstract

Major depressive disorder (MDD) is one of the most common psychiatric disorder, but the underlying mechanisms are largely unknown. Increasing evidence shows that brain-derived neurotrophic factor (BDNF) plays an important role in the structural plasticity induced by depression. Considering the opposite effects of BDNF and its precursor proBDNF on neural plasticity, we hypothesized that the balance of BDNF and proBDNF plays a critical role in chronic unpredicted mild stress (CUMS)-induced depressive-like behaviors and structural plasticity in the rodent hippocampus. The aims of this study were to compare the functions of BDNF and proBDNF in the CUMS-induced depressive-like behaviors, and determine the effects of BDNF and proBDNF on expressions of kalirin-7, postsynaptic density protein 95 (PSD95) and NMDA receptor subunit NR2B in the hippocampus of stressed and naïve control rats, respectively. Our results showed that CUMS induced depressive-like behaviors, caused a decrease in the ratio of BDNF/proBDNF in the hippocampus and resulted in a reduction in spine density in hippocampal CA1 pyramidal neurons; these alterations were accompanied by a decrease in the levels of kalirin-7, PSD95 and NR2B in the hippocampus. Injection of exogenous BDNF into the CA1 area of stressed rats reversed CUMS-induced depressive-like behaviors and prevented CUMS-induced spine loss and decrease in kalirin-7, NR2B and PSD95 levels. In contrast, injection of exogenous proBDNF into the CA1 region of naïve rats caused depressive-like behavior and an accompanying decrease in both spine density and the levels of kalirin-7, NR2B and PSD95. Taken together, our results suggest that the ratio of BDNF to proBDNF in the hippocampus plays a key role in CUMS-induced depressive-like behaviors and alterations of dendritic spines in hippocampal CA1 pyramidal neurons. Kalirin-7 may play an important role during this process.

p75NTR regulates brain mononuclear cell function and neuronal structure in Toxoplasma infection‐induced neuroinflammation

“…Interestingly, the precursor protein proBDNF was strongly increased upon infection. Particularly, signaling of proBDNF via the p75 NTR has been shown to promote spine pruning and to negatively affect dendritic spine density and synaptic plasticity (Orefice, Shih, Xu, Waterhouse, & Xu, ; Qiao, An, Xu, & Ma, ; Yang et al, ). In addition, our data imply that activated immune cells contribute to proBDNF production upon infection‐induced inflammation since previous studies also observed the secretion of proBDNF by peripheral macrophages under certain inflammatory conditions (Luo et al, ; Wong et al, ).…”

α7 nicotinic ACh receptors are necessary for memory recovery and neuroprotection promoted by attention training in amyloid‐β‐infused mice

“…In the present study, the blockade of α7nAChR significantly increased the neurotrophin levels in hippocampus. Once the method used detects total BDNF, this effect could be related to an increase in proBDNF that is known to reduce spine density and NMDA receptor and postsynaptic density protein 95 (Qiao, An, Xu, & Ma, ). So, this observation deserves further investigation.…”

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain‐derived neurotrophic factor

“…Studies have indicated an association between marked deficits in synaptic proteins and dysregulation of mTOR signaling in depressed subjects. Furthermore, activation of mTOR is associated with local protein synthesis in the synapse, promoting the expression of proteins for synaptic connections such as PSD95 (Qiao, An, Xu, & Ma, ). Of note, the behavioral data that indicate that antidepressant‐like effect of the SCF and SD (12 hr) is dependent on activation of mTOR was reinforced by western blot results.…”