Expression Levels Of Brain-derived Neurotrophic Factor Research Articles

원감, 수수 및 누에번데기 추출물로 조제된 조성물의 인지기능 개선 효과

Dementia including Alzheimer’s disease, is a severe neurodegenerative disorder characterized by progressive cognitive deficits as major symptom. The compositions (BBGS171) including extracts from root of Wongam (a Glycyrriza cultivar), seed of Sorghum bicolor (L.) pupae of Moench and Bombyx mori L. was selected based on preliminary experiments on the ability to improve cognition function in vitro. BBGS171 showed inhibitory activity on cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuchE) and inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-treated BV2 cells (a microglial cell line). The Y-maze test and passive avoidance test (PAT) were used to evaluate the behavior of an animal model of scopolamine-induced cognitive impairment. Rats administered BBGS171 (EM, extract mixture) in the diet showed better spontaneous alteration and escape latency than those of control rats. Levels of hippocampal choline acetyltransferase (ChAT) and serum acetylcholine (ACh) were significantly higher in the BBGS171 diet group than in the control group. Expression levels of brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) 1/2 in the hippocampus of the BBGS171 diet group were also higher than those of control group. These results suggest that BBGS171 (EM) could ameliorate cognition impairment and showed potential as a useful functional material.

Effects of Ozone on Hippocampus BDNF and Fos Expressions in Rats with Chronic Compression of Dorsal Root Ganglia.

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups (n = 12): sham operation (sham group), CCD group, CCD with 20 μg/ml of ozone (CCD + AO3 group), and CCD with 40 μg/ml of ozone (CCD + BO3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + AO3 and CCD + BO3 groups were injected with 100 μl of ozone with concentrations of 20 and 40 μg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group (P < 0.05). The TWLs and MWTs of the CCD + AO3 and CCD + BO3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group (P < 0.05). The TWLs were longer and the MWTs were higher in the CCD + BO3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + AO3 group (P < 0.05). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.

Effects of photoperiod and diet on BDNF daily rhythms in diurnal sand rats

Brain-derived neurotrophic factor (BDNF), its receptors and epigenetic modulators, are implicated in the pathophysiology of affective disorders, T2DM and the circadian system function. We used diurnal sand rats, which develop type 2 diabetes (T2DM), anxiety and depressive-like behavior under laboratory conditions. The development of these disorders is accelerated when animals are maintained under short photoperiod (5:19L:D, SP) compared to neutral photoperiod (12:12L:D, NP). We compared rhythms in plasma BDNF as well as BDNF and PER2 expression in the frontal cortex and suprachiasmatic nucleus (SCN) of sand rats acclimated to SP and NP. Acclimation to SP resulted in higher insulin levels, significantly higher glucose levels in the glucose tolerance test, and significantly higher anxiety- and depression-like behaviors compared with animals acclimated to NP. NP Animals exhibited a significant daily rhythm in plasma BDNF levels with higher levels during the night, and in BDNF expression levels in the frontal cortex and SCN. No significant BDNF rhythm was found in the plasma, frontal cortex or SCN of SP acclimated animals. We propose that in sand rats, BDNF may, at least in part, mediate the effects of circadian disruption on the development of anxiety and depressive-like behavior and T2DM.

Can Early Electrical Stimulation Accelerates the Neural Regeneration by Increasing the Expression of BDNF and GDNF in Distal Part of Injured Peripheral Nerve? An Animal Experimental Study

BACKGROUND: The role of neurotrophic factors (brain-derived neurotrophic factors and glial cell line-derived neurotrophic factors) and early electrical stimulation (EES) in the injured nerve has found promising in several studies. However, there is still limited knowledge about the effect of EES in the distal part of the nerve to sustain this level of expression of growth factors. AIM: We aim to evaluate the effects of EES in in neural regeneration by measuring the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in animal model. METHODS: The research was conducted starting from April to May 2021 using male Wistar rats. Using general anesthesia, the sciatic nerve was cut. The intervention group was treated with EES in the distal stump, right after nerve resection (20 Hz, 1–2 mA, 2–5 s), while the control group received no treatment after nerve resection. A reoperation on day 3 was performed in both groups to measure BDNF and GDNF expression level of the distal nerve tissue by ELISA as well as histopathological examination of sprouting axons of the injured proximal nerve. RESULTS: A total of 32 samples were included in the study. A statistically significant levels of GDNF is found higher in the EES group (n = 16) than the control group (n = 16) (35. 71 pg/100 mg, confidence interval (CI) 95% 23.93, 47.48, p &lt; 0.05). The number of sprouting axons is found lower in the EES group (p &lt; 0.05). The BDNF level is similar between the two groups, however not significant. After a subgroup analysis, it was found that the greater the level of GDNF, the fewer the axon sprouts in both groups (fewer axon group 58.35 [n = 22, CI 95% 45.14, 71.55] vs. more axon group 47.14 [n = 10, CI 95% 35.33, 58.95]), p &lt; 0.05. CONCLUSION: The EES proves its benefit in accelerating the axonal regeneration by increasing the expression GDNF in the distal nerve stumps in the electrical excited degenerated sciatic nerve in the rat model.

MiR-132-3p, miR-106b-5p, and miR-19b-3p Are Associated with Brain-Derived Neurotrophic Factor Production and Clinical Activity in Multiple Sclerosis: A Pilot Study.

Introduction: Brain-derived neurotrophic factor (BDNF) levels are reduced in advanced stages of multiple sclerosis (MS) and may be associated with reduced regenerative capability in progressive MS. This has brought increased attention to factors regulating BDNF production in MS. Our aim was to investigate the link between neurotrophin-regulating microRNAs (miRNA) and disease progression in MS. Materials and Methods: Serum levels of BDNF and peripheral blood mononuclear cell (PBMC) expression levels of miR-132-3p, miR-106b-5p and miR-19b-3p were respectively measured by ELISA and real time PCR in twelve relapsing remitting MS (RRMS) patients, seven secondary progressive MS (SPMS) patients and fourteen healthy controls. Results: Serum BDNF levels were significantly reduced in SPMS patients, while selected miRNAs were significantly upregulated in PBMC of RRMS and SPMS patients. miR-106b-5p and miR-19b-3p respectively showed the highest sensitivity and specificity for MS diagnosis by receiver operating characteristic curve analysis. There was a negative correlation between levels of BDNF and the miRNAs in RRMS. Likewise, levels of BDNF and the investigated miRNAs showed positive and negative correlations respectively with the expanded disability status scale in RRMS and SPMS patients. miR-132-3p and miR-106b-5p levels showed positive correlations with the progression index in SPMS patients. Conclusion: Our results suggest that increased disability is associated with downregulation of miR-132-3p, miR-106b-5p and miR-19b-3p in RRMS patients and putatively promotes increased production of neuroprotective BDNF as a compensatory mechanism. This link between the investigated miRNAs and BDNF in RRMS does not appears to hold for SPMS. This might be one of the factors contributing to reduced regenerative ability in the progressive stage of MS.

Effect of forced treadmill exercise on stimulation of BDNF expression, depression symptoms, tactile memory and working memory in LPS-treated rats

Neuroinflammation has been implicated in cognitive dysfunction and the occurrence of depression in neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is believed to be involved with the benefits of exercise training in boosting memory and learning processes and antidepressant therapies. This study aimed to investigate the effect of forced treadmill exercise on hippocampal BDNF expression levels, depression symptoms, tactile memory and working memory in lipopolysaccharide (LPS)-treated rats. For this purpose, 40 male Wistar rats received 0.25 mg/kg of LPS or saline intraperitoneally for 9 consecutive days before exercise. They again received a single injection of 0.5 mg/kg of LPS or saline on days 20 and 41 after exercise. Exercise groups had to run on a motorized treadmill 5 days a week for 8 weeks. Following the last exercise training session, forced swim test (FST), Y maze and novel object recognition (NOR) task were performed. Finally, the hippocampus of rats was removed and used for determination of BDNF expression levels by real-time polymerase chain reaction (real-time PCR). The data showed that LPS decreased BDNF expression levels, Y maze score, and recognition index in NOR and increased immobility time in FST (p < 0.05). In contrast, forced treadmill exercise increased BDNF expression levels and improved the percentage of spontaneous alternation, recognition index, and immobility time in LPS-treated rats (p < 0.05). There was a significant correlation between BDNF expression levels with immobility time and recognition index (p < 0.05) but not with the percentage of spontaneous alternation (p > 0.05). The findings suggest that forced treadmill exercise may protect the brain of LPS-treated rats by improving the symptoms of depression and cognitive function through its effect on BDNF expression levels.

Effects of long-term infliximab and tocilizumab treatment on anxiety-like behavior and cognitive function in naive rats.

Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.

The Effect of Emotional Intelligence on Facial Expression Recognition: An ERP Study

Brain-derived neurotrophic factor (BDNF), its receptors and epigenetic modulators, are implicated in the pathophysiology of affective disorders, T2DM and the circadian system function. We used diurnal sand rats, which develop type 2 diabetes (T2DM), anxiety and depressive-like behavior under laboratory conditions. The development of these disorders is accelerated when animals are maintained under short photoperiod (5:19L:D, SP) compared to neutral photoperiod (12:12L:D, NP). We compared rhythms in plasma BDNF as well as BDNF and PER2 expression in the frontal cortex and suprachiasmatic nucleus (SCN) of sand rats acclimated to SP and NP. Acclimation to SP resulted in higher insulin levels, significantly higher glucose levels in the glucose tolerance test, and significantly higher anxiety- and depression-like behaviors compared with animals acclimated to NP. NP Animals exhibited a significant daily rhythm in plasma BDNF levels with higher levels during the night, and in BDNF expression levels in the frontal cortex and SCN. No significant BDNF rhythm was found in the plasma, frontal cortex or SCN of SP acclimated animals. We propose that in sand rats, BDNF may, at least in part, mediate the effects of circadian disruption on the development of anxiety and depressive-like behavior and T2DM.

Olfactory learning and memory in the greater short-nosed fruit bat Cynopterus sphinx: the influence of conspecifics distress calls.

This study was designed to test whether Cynopterus sphinx distress calls influence olfactory learning and memory in conspecifics. Bats were exposed to distress calls/playbacks (PBs) of distress calls/modified calls and were then trained to novel odors. Bats exposed to distress calls/PBs made significantly fewer feeding attempts and bouts of PBs exposed to modified calls, which significantly induced the expression of c-Fos in the caudomedial neostriatum (NCM) and the amygdala compared to bats exposed to modified calls and trained controls. However, the expression of c-Fos in the hippocampus was not significantly different between the experimental groups. Further, protein phosphatase-1 (PP-1) expression was significantly lower, and the expression levels of E1A homologue of CREB-binding protein (CBP) (P300), brain-derived neurotrophic factor (BDNF) and its tyrosine kinase B1 (TrkB1) receptor were significantly higher in the hippocampus of control/bats exposed to modified calls compared to distress calls/PBs of distress call-exposed bats. Exposure to the call possibly alters the reciprocal interaction between the amygdala and the hippocampus, accordingly regulating the expression levels of PP1, P300 and BDNF and its receptor TrkB1 following training to the novel odor. Thus, the learning and memory consolidation processes were disrupted and showed fewer feeding attempts and bouts. This model may be helpful for understanding the contributions of stressful social communications to human disorders.

Effect of BDNF on airway inflammation in a rat model of COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. The present study aimed to investigate the effect of brain-derived neurotrophic factor (BDNF) on lung function and airway inflammation in a rat model of COPD. A rat model of COPD was established in this study, and anti-BDNF antibody was injected to observe the effect of BDNF on pulmonary function and airway inflammation. Lung function and hematoxylin and eosin staining analyses were performed. BDNF in the airway was examined using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Levels of oxidant stress and inflammatory cytokines were measured. After long-term heavy cigarette exposure, pulmonary inflammation and emphysema were observed, while lung function had deteriorated in the COPD, COPD + anti-BDNF and COPD + normal saline groups. Levels of BDNF expression, malondialdehyde, tumor necrosis factor-α and interleukin-6 were increased in rats with COPD compared with control rats, while levels of superoxide dismutase and glutathione peroxidase were decreased. Anti-BDNF intervention improved airway inflammation. To conclude, anti-BDNF intervention could alleviate inflammation and improve any imbalance between oxidation and antioxidation in the airway.

Ventral tegmental area serotonin 5-HT1A receptors and corticolimbic cFos/BDNF/GFAP signaling pathways mediate dextromethorphan/morphine anti-allodynia

AimsThe present study examined the role of ventral tegmental area (VTA) serotonergic 5HT1A receptors in dextromethorphan/morphine-induced anti-allodynia and the possible changes of corticolimbic cFos, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) following the treatments. Materials and methodsThe VTA cannulation and the chronic constriction of the sciatic nerve were performed in male Wistar rats. Flexion withdrawal thresholds to mechanical stimulation in the hind-limb were determined using von Frey hairs. The expressions of cFos, BDNF, and GFAP were evaluated using the Western blotting technique. Key findingsBDNF (in the hippocampus), and GFAP (in the targeted sites) levels were increased following neuropathic pain. Morphine administration induced an anti-allodynic effect with a decrease in the amygdala BDNF level. Dextromethorphan/morphine-induced anti-allodynia was accompanied by the decrease of hippocampus/amygdala/PFC GFAP and amygdala cFos expressions. The PFC BDNF expression level was increased in dextromethorphan/morphine-treated rats. Intra-VTA microinjection of (S)-WAY100135 (1 µg/rat), a selective 5-HT1A receptor antagonist, inhibited the anti-allodynic effect of dextromethorphan/morphine. This treatment increased the cFos level in the hippocampus and the amygdala while decreased the PFC level of cFos. The hippocampal BDNF expression was significantly increased, while the amygdala and the PFC expressions of BDNF were decreased under treatment. (S)-WAY100135 plus dextromethorphan/morphine increased the hippocampal/amygdala and PFC levels of GFAP. SignificanceThese findings indicate that dextromethorphan could potentiate the analgesic effect of morphine via the implication of the VTA serotonin 5-HT1A receptors. It seems that the changes in the corticolimbic cFos/BDNF/GFAP signaling pathway may be involved in the observed anti-allodynic effect.

Long Non-coding RNA LINC01119 Promotes Neuropathic Pain by Stabilizing BDNF Transcript.

Neuropathic pain (NP) is caused by primary injury or dysfunction of the peripheral and the central nervous system. Long non-coding RNAs were critical regulators involved in nervous system diseases, however, the precise regulatory mechanism remains unclear. This study aims to uncover the essential role of LINC01119 in NP progression and further clarify the underlying regulatory mechanism at post-transcriptional level. LINC01119 was significantly upregulated in rats of spare nerve injury (SNI) group compared to sham group. Functionally, silencing of LINC01119 significantly alleviated the neuropathic pain-induced hypersensitivity and reduced the increase in IL−6, IL−1β, and TNF−α caused by SNI. Mechanistically, Brain-derived neurotrophic factor (BDNF) was identified as the functional target of LINC01119. Besides, an RNA binding protein, ELAVL1 could directly interact with LINC01119, and this formed LINC01119- ELAVL1 complex binds to BDNF mRNA, strengthening its RNA stability and increasing the expression level of BDNF at both transcript and protein levels. Clinically, serum LINC01119 was verified as a promising diagnostic biomarker for NP patients. LINC01119 induces NP progression via binding with ELAVL1 and increasing BDNF mRNA stability and expression level. Therefore, LINC01119 may serve as a promising diagnostic marker and therapeutic target for NP treatment.

Caesalpinia sappan L. Ameliorates Scopolamine-Induced Memory Deficits in Mice via the cAMP/PKA/CREB/BDNF Pathway

Memory is an essential aspect of human cognition. A decrease in this aspect is well associated with Alzheimer’s disease (AD). The development of a novel cognitive enhancer (CE) may help overcome AD-related problems. In this study, we evaluated the CE effect of Caesalpinia sappan L. (CS) in memory deficit mice. Administration of its ethanolic extract (250 and 500 mg/kg body weight (BW)) and brazilin (5 and 10 mg/kg BW) ameliorated the scopolamine-amnesic effect, as evidenced by significant decreases (p &lt; 0.01, p &lt; 0.05) in the escape latency time and increases (p &lt; 0.01) in the percentage of time spent in the target quadrant of the Morris water maze test. We also examined the cyclic adenosine monophosphate (cAMP) level, protein kinase A (PKA) activity, and protein expression levels of phosphorylated cAMP response element binding (pCREB) and brain-derived neurotrophic factor (BDNF) in hippocampal tissues to elucidate the underlying molecular mechanism. Results showed that CS wood ethanolic extract and brazilin not only significantly increase (p &lt; 0.01, p &lt; 0.05) cAMP levels and PKA activity but also significantly enhance (p &lt; 0.01, p &lt; 0.05) the expression level of pCREB and BDNF in the hippocampus. These findings indicate that CS activates the cAMP/PKA/CREB/BDNF pathway. Taken together, our results demonstrate that CS is a promising herb that could be developed as a CE agent.

Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats.

Preconditioning exercise prior to stroke exerts neuroprotection, which is an endogenous strategy that leads the brain cells to express several intrinsic factors and inhibits their apoptosis. However, it is unclear how long these benefits last after exercise cessation. The aim of this study was to investigate the effects of detraining on preconditioning exercise-induced neuroprotective potential after stroke. Rats were trained using a treadmill for aerobic exercise 5days each week for 3weeks, and their neuroprotective effects were examined until 3weeks after exercise cessation. Stroke was induced by 60min of left middle cerebral artery occlusion at 3days, 1, 2, and 3weeks after exercise cessation. Infarct volume, neurological deficits, sensorimotor function, expression levels of brain-derived neurotrophic factor (BDNF), hypoxia-induced factor-1α (HIF-1α), glial fibrillary acidic protein (GFAP), and P2X7 receptors, and apoptosis activity were examined using immunohistochemical and western blot analyses. Preconditioning exercise significantly reduced infarct volume and ameliorated sensorimotor function after stroke, and its beneficial effects were observed until 2weeks after exercise cessation. The expression level of BDNF in the ischemic brain was significantly upregulated at 3days after exercise cessation; however, the expression levels of HIF-1α, GFAP, and P2X7 receptor were significantly increased until 2weeks after exercise cessation; thereby, significant anti-apoptotic effects were lost at 3weeks of detraining. Our findings suggest that preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. Neuroprotection through intrinsic protective factors, such as BDNF and HIF-1α, may provide different neuroprotective mechanisms in a time-dependent manner during detraining.

Effects of different implant surface properties on the biological behavior of Schwann cells.

This study investigated the effects of different implant surface properties on the biological behavior of Schwann cells. Schwann cells (SCs) were cultured on three types of implant surfaces including smooth polished (SMO), sand-blasted, large grit, acid-etched (SLA), and chemically-modified SLA (modSLA). At different time points, the morphology and adhesion of SCs on the implant surfaces were observed by scanning electron microscope. Cell proliferation activity was detected by MTT method. The expression levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were detected by enzyme-linked immunosorbent assay. Changes in the mRNA levels of NGF and BDNF were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). SCs adhered, stretched, and proliferated well on the three types of implant surfaces. On the 3rd, 5th, and 7th days, the OD values of the SMO group were higher than those of the SLA group and the modSLA group, and the difference was statistically significant (P<0.05). On the 3rd day, the expression and mRNA levels of NGF and BDNF in the SLA group and the modSLA group were higher than those in the SMO group (P<0.05); in particular, the levels in the modSLA group were higher than those in the SLA group (P<0.05). Different implant surface properties have different effects on the biological behavior of SCs. Proliferation of SCs is significantly promoted by smooth surface, while secretion and gene expression of neurotrophic factors are significantly promoted by modSLA surface at early stage.

Hospital-based case control study and animal study on the relationship between nonylphenol exposure and depression.

ObjectivesThe aim of this work is to explore the association between chronic exposure to nonylphenol (NP), a representative environmental endocrine disruptor (EED), and the risk of depression and its potential mechanism.MethodsA hospital-based case control study was conducted from August to December 2018. Forty-one patients with confirmed depression and 47 healthy volunteers were recruited. In vitro, 20 rats were randomly divided into the control group (corn oil) and NP exposure group (n=10 per group), which were gavaged at a dose of 4 mg/kg w/day for 180 days.ResultsThe depressed patient group had higher Zung Self-Rating Depression Scale (SDS) (P<0.001) and Self-Rating Anxiety Scale (SAS) (P<0.001) scores than the healthy group. The serum NP level (P=0.009) in the depressed group was higher than that in the healthy group, and the BDNF level (P=0.001) was lower. The serum levels of monoamine neurotransmitters dopamine (DA) (P=0.070), epinephrine (E) (P=0.001), and noradrenaline (NE) (P=0.000) were lower than those in the healthy group. In the sucrose preference test, the sucrose preference time for the exposure group of rats was lower than that of the control group (P<0.001). In the forced swim test, a longer resting time was measured for the exposure group of rats as compared to the control group (P<0.05). The level of NP (P<0.001) in the brain tissue of the NP exposure group was higher than that in the control group, and the serum level of brain-derived neurotrophic factor (BDNF) (P=0.004) was lower. Histopathological examination of the brain biopsies illustrated that the neuronal cells and nuclei in the hippocampus of the exposed group exhibited slight shrinkage.ConclusionChronic exposure to NP at environmental doses will result in the accumulation of NP in the brain and blood, and induction of depression, which might be associated with the alterations in the expression levels of BDNF and monoamine neurotransmitters.

Reversible Changes in BDNF Expression in MK-801-Induced Hippocampal Astrocytes Through NMDAR/PI3K/ERK Signaling.

Dizocilpine (MK-801), a non-competitive N-methyl-D-aspartic acid receptor (NMDA-R) antagonist, can induce schizophrenia-like symptoms in healthy individuals, implicating NMDA-R hypofunction in disease pathogenesis. Brain-derived neurotrophic factor (BDNF) is also implicated in schizophrenia, and expression is regulated by NMDA-R activity, suggesting a functional link. We previously found that BDNF signaling was upregulated by MK-801 in cultured hippocampal astrocytes, but the underlying mechanism is not clear. To address this issue, the levels of BDNF expression and secretion were evaluated in hippocampal astrocytes incubated with MK-801 by ELISA and qPCR, with and without NMDA co-incubation or pretreatment of either the ERK1/2 inhibitor, PD98059 or the PI3K inhibitor, LY294002. The apoptosis, viability, and proliferation of the astrocytes were also examined. In the current study, we demonstrate that MK-801 treatment (20 μM for 5 days) enhances the proliferation of rat cultured hippocampal astrocytes. Expression of BDNF mRNA was enhanced after 24 h in MK-801, but returned to near baseline over the next 24 h in the continued presence of MK-801. However, two successive 24-h treatments enhanced BDNF expression. These application regimens had no effect on apoptosis or proliferation rate. Co-addition of NMDA significantly inhibited MK-801-induced upregulation of BDNF. Similarly, MK-801-induced BDNF upregulation was blocked by pretreatment with inhibitors of PI3K and ERK1/2, but not by inhibitors of p38 and JNK. These findings suggested that astrocytes may contribute to the acute neurological and behavioral response to MK-801 treatment via a transient increase in BDNF expression involving NMDA-R–PI3K–ERK signaling.

The Val66 and Met66 Alleles-Specific Expression of BDNF in Human Muscle and Their Metabolic Responsivity.

Brain-derived neurotrophic factor (BDNF) plays an essential role in nervous system formation and functioning, including metabolism. Present only in humans, the “Val66Met” polymorphism of the BDNF gene (BDNF) is suggested to have a negative influence on the etiology of neurological diseases. However, this polymorphism has only been addressed, at the molecular level, in nonhuman models. Knowledge about Val66- and Met66-variant differences, to date, has been achieved at the protein level using either cell culture or animal models. Thus, the purpose of our study was to analyze the impact of the Val66Met polymorphism on BDNF expression in healthy humans and compare the allele-specific responses to metabolic stress. Muscle biopsies from 13 male recreational athletes (34 ± 9 years, 1.80 ± 0.08 m, 76.4 ± 10.5 kg) were obtained before and immediately following a VO2max test. Allele-specific BDNF mRNA concentrations were quantified by droplet digital PCR (ddPCR) in heterozygous and homozygous subjects. The results indicated that BDNF expression levels were influenced by the genotype according to the presence of the polymorphism. BDNF expression from the Met66-coding alleles, in heterozygotes, was 1.3-fold lower than that from the Val66-coding alleles. Total BDNF mRNA levels in these heterozygotes remained below the whole sample’s mean. A partial dominance was detected for the Val66-coding variant on the Met66-coding’s. BDNF expression levels decreased by an average of 1.8-fold following the VO2max test, independent of the individual’s genotype. The results of this study indicate that metabolic stress downregulates BDNF expression but not plasma BDNF concentrations. No correlation between expression level and plasma BDNF concentrations was found.

Long noncoding RNA LOC100911498 is a novel regulator of neuropathic pain in rats.

IntroductionNeuropathic pain (NP) is the most debilitating of all clinical pain syndromes and may be a consequence of dysfunction in the somatosensory nervous system. Unfortunately, the pathogenesis of NP is not fully understood yet and it cannot be cured totally. Long noncoding RNA (lncRNA) is a type of RNA molecule greater than 200 nucleotides, and dysregulated expression of lncRNAs play a critical role in the facilitation of NP. Previous study showed the expression level of LOC100911498 in the spinal cords of spared nerve injury (SNI) rats were increased. This research was aimed at exploring what role LOC100911498 plays in the pathophysiological process of NP.MethodsThe mechanical withdrawal threshold (MWT) of rats was measured by the von Frey test. The expression levels of P2X4 receptor (P2X4R), ionized calcium‐binding adaptor molecule 1 (Iba‐1), p‐p38 and brain‐derived neurotrophic factor (BDNF) in spinal cords were detected, respectively.ResultsOur results suggested that the level of LOC100911498 in SNI rats was markedly higher than that in the sham group; the MWT values in rats were treated with LOC100911498siRNA were increased, and the expression levels of P2X4R, Iba‐1, p‐p38 and BDNF in SNI+ LOC100911498siRNA group were reduced compared with those in the SNI group.ConclusionOur study indicated the effects lncRNA LOC100911498 siRNA exerted on NP were mediated by P2X4R on microglia in the spinal cords of rats. Further, LOC100911498 may be a novel positive regulator of NP by regulating the expression and function of the P2X4R.

Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics.

Vascular dementia, caused by cerebrovascular disease, is associated with cognitive impairment and reduced hippocampal metabolite levels. Specifically, cognitive impairment can be induced by decreased hippocampal brain-derived neurotrophic factor (BDNF) expression. The development of low or non-invasive biomarkers to characterize these diseases is an urgent task. Disturbance of metabolic pathways has been frequently observed in cognitive impairment, and salivary molecules also showed the potentials to reflect cognitive impairment. Therefore, we evaluated salivary metabolic profiles associated with altered hippocampal BDNF expression levels in a cerebral ischemia mouse model using metabolomic analyses. The effect of tacrine (a cholinesterase inhibitor) administration was also examined. The arteries of ICR mice were occluded with aneurysm clips to generate the cerebral ischemia model. Learning and memory performance was assessed using the elevated plus maze (EPM) test. Hippocampal and blood BDNF levels were quantified using an enzyme-linked immunosorbent assay. Glutamate decarboxylase 1 (GAD1) mRNA expression, is associated with cognitive impairment, was quantified by a real-time polymerase chain reaction. The EPM test revealed impaired spatial working memory in the cerebral ischemia mouse model; tacrine administration ameliorated this memory impairment. Cerebral ischemia suppressed GAD1 expression by decreasing hippocampal BDNF expression. In total, seven salivary metabolites, such as trimethylamine N-oxide and putrescine, were changed by cognitive impairment and tacrine administration. Our data suggest that salivary metabolite patterns were associated with cognitive function.