Differences in the Biological Functions of BDNF and proBDNF in the Central Nervous System

Borodinova, Anastasia A.; Саложин, С. В.

doi:10.1007/s11055-017-0391-5

Cited by 28 publications

(27 citation statements)

References 97 publications

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“…One of the typical signaling pathways downstream of the β2-AR activation involves pCREB at Ser-133 (pCREB) and facilitates the transcription of BDNF. BDNF is synthesized as a precursor molecule (proBDNF), and then cleaved into mature BDNF within endoplasmic reticulum, which plays an important role in synaptic plasticity and neuronal survival (Borodinova and Salozhin, 2017; Li et al, 2019). As shown in Figure 2B, sepsis significantly decreased the expressions of pCREB ( F 5,12 = 14.95, p < 0.001) and the ratio of mBDNF/proBDNF ( F 5,12 = 8.32, p = 0.001) at 24 h and persisted until 16 days following CLP.…”

Section: Resultsmentioning

confidence: 99%

Activation of β2-Adrenoceptor Attenuates Sepsis-Induced Hippocampus-Dependent Cognitive Impairments by Reversing Neuroinflammation and Synaptic Abnormalities

Zong

Zhou

et al. 2019

Front. Cell. Neurosci.

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Sepsis-associated encephalopathy induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation and synaptic plasticity impairment of the hippocampus. The β2-adrenoceptor (β2-AR) is a G-protein coupled receptor that regulates immune response and synaptic plasticity, whereas its dysfunction has been implicated in various neurodegenerative diseases. Thus, we hypothesized abnormal β2-AR signaling is involved in sepsis-induced cognitive impairment. In the present study, C57BL/6 mice were subjected to cecal ligation and puncture (CLP) to mimic the clinical human sepsis-associated encephalopathy. The levels of hippocampal β2-AR, proinflammatory cytokines tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, cAMP-response element binding protein (CREB), brain derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95), and NMDA receptor 2 B subtypes (GluN2B) were determined at 6, 12, 24 h and 7 and 16 days after CLP. For the interventional study, mice were treated with β2-AR agonist clenbuterol in two ways: early treatment (immediately following CLP) and delayed treatment (on the 8th day following CLP). Neurobehavioral performances were assessed by open field and fear conditioning tests. Here, we found that hippocampal β2-AR expression was significantly decreased starting from 12 h and persisted until 16 days following CLP. Besides, sepsis mice also exhibited increasing neuroinflammation, down-regulated CREB/BDNF, decreasing PSD95 and GluN2B expression, and displayed hippocampus-dependent cognitive impairments. Notably, early clenbuterol treatment alleviated sepsis-induced cognitive deficits by polarizing microglia toward an anti-inflammatory phenotype, reducing proinflammatory cytokines including IL-1β, TNF-α, and up-regulating CREB/BDNF, PSD95, and GluN2B. Intriguingly, delayed clenbuterol treatment also improved cognitive impairments by normalization of hippocampal CREB/BDNF, PSD95, and GluN2B. In summary, our results support the beneficial effects of both early and delayed clenbuterol treatment, which suggests that activation of β2-AR has a translational value in sepsis-associated organ dysfunction including cognitive impairments.

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Section: Resultsmentioning

confidence: 99%

Activation of β2-Adrenoceptor Attenuates Sepsis-Induced Hippocampus-Dependent Cognitive Impairments by Reversing Neuroinflammation and Synaptic Abnormalities

Zong

Zhou

et al. 2019

Front. Cell. Neurosci.

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“…Selective testing revealed epigenetic changes in the promoter regions of some "plasticity relat ed genes" (Bdnf, Reln) coupled with the increase in their transcription and translation. Products of these genes could participate in the changes of structural characteris tics and efficiency of connections between the neurons [30,31]. In another work, a rapid but reversible increase in the acetylation of histones was observed in the orbitofrontal cortex of animals following learning [23].…”

Section: Spatial Temporal Epigenetic Rearrangements In Functional Neumentioning

confidence: 91%

Epigenetic Regulation as a Basis for Long-Term Changes in the Nervous System: In Search of Specificity Mechanisms

Borodinova

Balaban

2020

Biochemistry Moscow

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Adaptive long-term changes in the functioning of nervous system (plasticity, memory) are not written in the genome, but are directly associated with the changes in expression of many genes comprising epigenetic regulation. Summarizing the known data regarding the role of epigenetics in regulation of plasticity and memory, we would like to highlight several key aspects. (i) Different chromatin remodeling complexes and DNA methyltransferases can be organized into high-order multiprotein repressor complexes that are cooperatively acting as the “molecular brake pads”, selectively restricting transcriptional activity of specific genes at rest. (ii) Relevant physiological stimuli induce a cascade of biochemical events in the activated neurons resulting in translocation of different signaling molecules (protein kinases, NO-containing complexes) to the nucleus. (iii) Stimulus-specific nitrosylation and phosphorylation of different epigenetic factors is linked to a decrease in their enzymatic activity or changes in intracellular localization that results in temporary destabilization of the repressor complexes. (iv) Removing “molecular brakes” opens a “critical time window” for global and local epigenetic changes, triggering specific transcriptional programs and modulation of synaptic connections efficiency. It can be assumed that the reversible post-translational histone modifications serve as the basis of plastic changes in the neural network. On the other hand, DNA methylation and methylation-dependent 3D chromatin organization can serve a stable molecular basis for long-term maintenance of plastic changes and memory.

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“…Meanwhile, brain-derived neurotrophic factor (BDNF) is well known as an important molecule during synapse development and plasticity [15]. This molecule stimulates the neural regeneration as well as enhanced the cognitive and memory function in mammalian system through the interaction with TrkB [16]. However, the precursor of BDNF (pro-BDNF) exhibits opposite biological function of BDNF via the interaction mainly with p75 NTR [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…This molecule stimulates the neural regeneration as well as enhanced the cognitive and memory function in mammalian system through the interaction with TrkB [16]. However, the precursor of BDNF (pro-BDNF) exhibits opposite biological function of BDNF via the interaction mainly with p75 NTR [16,17]. Especially, BDNF has the ability to cross blood-brain barrier (BBB) and be stably maintained in blood up to 60 min after intravenous injection [18].…”

Section: Introductionmentioning

confidence: 99%

Anti-Oxidant Activity of Gallotannin-Enriched Extract of Galla Rhois Can Associate with the Protection of the Cognitive Impairment through the Regulation of BDNF Signaling Pathway and Neuronal Cell Function in the Scopolamine-Treated ICR Mice

et al. 2019

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The antibacterial, anti-inflammatory, anti-metastatic/anti-invasion activities and laxative activity of Galla Rhois (GR) are well-known, although the neuropreservation effects of their extracts are still to be elucidated. To investigate the novel therapeutic effects and molecular mechanism of GR on alleviation of cognitive impairment, two different dosages of gallotannin-enriched GR (GEGR) were administered to Korl:ICR mice for three weeks, and to induce memory impairment, scopolamine (SP) was administered during the last seven days of the GEGR treatment period. GEGR showed the high level of the free radical scavenging activity to DPPH and suppressive activity to reactive oxygen species (ROS) in B35 cells as well as enhanced SOD and CAT activity in brains of the SP-induced model. Latency time for memory impairment assessed by the passive avoidance test significantly protected in the SP+GEGR treated group as compared to the SP+Vehicle treated group. Moreover, similar protective effects were observed on the secretion of BDNF in SP+GEGR treated mice. The expression of TrkB receptor, and phosphorylation of PI3K on the TrkB receptor signaling pathway were dramatically protected in the SP-induced model after GEGR treatment, whereas the expression of p75NTR receptor, the phosphorylation of JNK, and expression of Bax/Bcl-2 on the p75NTR receptor signaling pathway was significantly protected in the same group. Furthermore, the GEGR treated SP-induced model showed decreased number of dead neural cells and suppressed acetylcholine esterase (AChE) activity and inhibited inflammatory responses. Taken together, these results indicate that the anti-oxidant activity of GEGR contributes to improving the neuronal cell function and survival during cognitive impairment in the SP-induced model through regulation of BDNF secretion and their receptor signaling pathway.

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Differences in the Biological Functions of BDNF and proBDNF in the Central Nervous System

Cited by 28 publications

References 97 publications

Activation of β2-Adrenoceptor Attenuates Sepsis-Induced Hippocampus-Dependent Cognitive Impairments by Reversing Neuroinflammation and Synaptic Abnormalities

Activation of β2-Adrenoceptor Attenuates Sepsis-Induced Hippocampus-Dependent Cognitive Impairments by Reversing Neuroinflammation and Synaptic Abnormalities

Epigenetic Regulation as a Basis for Long-Term Changes in the Nervous System: In Search of Specificity Mechanisms

Anti-Oxidant Activity of Gallotannin-Enriched Extract of Galla Rhois Can Associate with the Protection of the Cognitive Impairment through the Regulation of BDNF Signaling Pathway and Neuronal Cell Function in the Scopolamine-Treated ICR Mice

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