Protective effect of brain-derived neurotrophic factor on retinal neurovascular unit / 国际眼科杂志(Guoji Yanke Zazhi)

Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.

Asociación entre el polimorfismo Val66Met del gen BDNF y el desarrollo de disfunción ejecutiva en pacientes con cáncer de mama

Introducción. La disfunción ejecutiva asociada a quimioterapia es un efecto adverso del tratamiento antineoplásico convencional y afecta a un porcentaje considerable de personas. Se ha reportado que la presencia de ciertos polimorfismos en genes relevantes puede causar mayor susceptibilidad a padecerlo. Objetivo. Determinar la relación entre el polimorfismo Val66Met (196 G>A) del gen BDNF y el desarrollo de disfunción ejecutiva en mujeres con cáncer de mama tratadas con quimioterapia. Métodos. Se evaluaron a 73 pacientes mujeres con cáncer de mama para determinar disfunción ejecutiva antes y después de la quimioterapia. La evaluación fue realizada con la prueba INECO Frontal Screening (IFS). Se determinó el genotipo (GG=Val/Val, GA=Val/Met y AA=Met/Met) por PCR y secuenciamiento del gen BDNF. El análisis de asociación se realizó mediante el cálculo del odds ratio (OR). Resultados. El 13,7% (n = 10) de pacientes presentó el alelo A (GA y AA), además obtuvieron puntajes significativamente menores de la prueba IFS comparado con las homocigotas GG (p A) del gen BDNF y el desarrollo de disfunción ejecutiva en pacientes con cáncer de mama tratadas con quimioterapia; sin embargo, las portadoras del alelo A (Met) presentaron puntajes menores en la evaluación cognitiva.

Introduction. Chemotherapy-associated executive dysfunction is an adverse effect of conventional antineoplastic treatment that affects many patients. It has been reported that the presence of specific polymorphisms in key genes can cause a greater susceptibility to develop this condition. Objective. To determine the relationship between the Val66Met polymorphism (196 G>A) of the BDNF gene and the development of executive dysfunction in female patients with breast cancer treated with chemotherapy. Methods. 73 female breast cancer patients were evaluated for executive dysfunction before and after chemotherapy. The evaluation was carried out with the INECO Frontal Screening test (IFS). The genotype (GG=Val/Val, GA=Val/Met and AA=Met/Met) was determined by PCR and sequencing of BDNF gene. Association analysis was performed by calculating the Odds Ratio (OR) and by quantitative comparison. Results. 13.7% (n = 10) of the sample presented the allele A (GA and AA), which obtained significantly lower scores in the IFS test compared to the homozygous GG (p A) polymorphism of the BDNF gene and the development of executive dysfunction in patients with breast cancer treated with chemotherapy. However, patients with the allele A (Met) presented significant lower scores in the cognitive assessment.

Effects of Jieyu Zhitong Prescription on behavior and BDNF/ERK1/2/CREB signaling pathway in migraine-depressive comorbid model rats / 国际中医中药杂志

Objective:To observe the effects of Jieyu Zhitong Prescription on the behavior of migraine-depressed comorbid model rats; To explore its mechanism from the perspective of regulating brain derived neurotrophic factor (BDNF)/ERK1/2/cyclic adenosine responsive element binding protein (CREB) signaling pathway.Methods:Totally 36 SD male rats were divided into blank group, model group, nimodipine group and low-, medium-and high-dose group of Chinese medicine according to random number table method. The migraine-depressive comorbidity model was replicated by intermittent subcutaneous injection of nitroglycerin (10 mg/kg) and chronic unpredictable mild stimulation. Rats in each group were given corresponding drug intervention for 21 days, once a day. The weight of rats in each group before and on the 10th and 21st days after modeling was recorded. The threshold of mechanical pain was detected, and the behavior of rats was evaluated by open field test, forced swimming test, and novelty inhibition feeding test. The protein expressions of BDNF, TrKB, p-ERK1/2 and p-CREB in rat hippocampus were detected by Western blot.Results:On the 10th and 21st day of modeling intervention, compared with model group, the body weight, the scores of horizontal and vertical activity in open field experiment in each dose group of Chinese medicine increased ( P<0.05), and the latent time of novelty inhibition feeding and immobile time of forced swimming were shortened ( P<0.05). On the 7th, 14th and 21st days, compared with the model group at the same time point, the threshold of mechanical pain of rats in each dose group of Chinese medicine increased ( P<0.05). The expression of p-ERK1/2 protein increased in hippocampal tissue in each dose group of Chinese medicine ( P<0.05), and the expression of BDNF, TrkB, and p-CERB protein increased in the low- and high-dose group of Chinese medicine ( P<0.05). Conclusion:Jieyu Zhitong Prescription can significantly improve the symptoms of migraine-depressed comorbid rats, and its mechanism may be analgesic and antidepressant by affecting the expression of proteins in the BDNF/ERK1/2/CREB signaling pathway.

Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor / 南方医科大学学报

OBJECTIVE@#To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism.@*METHODS@#Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining.@*RESULTS@#Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05).@*CONCLUSION@#The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.

Effects of Electroacupuncture on Hippocampal AcH3 and BDNF in the Rat Model of SNI-induced Pain-Depression Dyad / 中山大学学报(医学科学版)

ObjectiveTo observe the impacts of electroacupuncture （EA） on the expression of hippocampal brain-derived neurotrophic factor （BDNF） and acetylated histone （AcH3） in the rat model of spared nerve injury （SNI）， so as to explore the analgesic and antidepressant effects of EA. MethodsTwenty-four Male SD rats were randomly divided into 4 groups， with 6 in each group. SNI was used to establish the model of pain and depression. All the groups were intervened one week after SNI surgery and persisted 5 weeks. The EA group was treated with EA （2 Hz） for 30 min every other day and imipramine drug group （IMP） group with peritoneal imipramine injection （10 mg/kg） per day. The sham surgery group （SS） and model group （SNI） received the same grasping stimulation. The paw mechanical withdrawal threshold （PWT） test was performed before the SNI surgery， 1， 2， 3， 4， 5， and 6 weeks after surgery， respectively. The forced swimming test （FST） and the sucrose preference test （SPT） were performed 6 weeks after SNI surgery. The Western blot method was employed to detect the expression of BDNF and AcH3 from the rat hippocampal tissue at the end of the behavioral tests. ResultsCompared with the SS group， the SNI group had significantly decreased PWT and sucrose consumption， prolonged FST immobility time （all P<0.01）， down-regulated BDNF and AcH3 expression （P<0.05 & P<0.01） in the hippocampus， which indicated the successful construction of the pain-depression model. Compared with the SNI group， 6 weeks after SNI surgery， the EA and IMP groups had significantly increased PWT and sucrose consumption， and reduced FST immobility time （all P<0.01）； the EA group had up-regulated BDNF and AcH3 expression （both P<0.05） in the hippocampus， the IMP group had up-regulated AcH3 （P<0.05） expression but no difference in BDNF expression. ConclusionEA could relieve pain and depressive behavioral symptoms in SNI rats. And its analgesic and antidepressant mechanisms may relate to the up-regulation of hippocampal AcH3 and BDNF expression.

Brain-derived neurotrophic factor interplay with oxidative stress: neuropathology approach in potential biomarker of Alzheimer's disease / Interação do fator neurotrófico encefálico com o estresse oxidativo: abordagem neuropatológica a um potencial biomarcador da doença de Alzheimer

ABSTRACT The aging population poses a serious challenge concerning an increased prevalence of Alzheimer's disease (AD) and its impact on global burden, morbidity, and mortality. Oxidative stress, as a molecular hallmark that causes susceptibility in AD, interplays to other AD-related neuropathology cascades and decreases the expression of central and circulation brain-derived neurotrophic factor (BDNF), an essential neurotrophin that serves as nerve development and survival, and synaptic plasticity in AD. By its significant correlation with the molecular and clinical progression of AD, BDNF can potentially be used as an objectively accurate biomarker for AD diagnosis and progressivity follow-up in future clinical practice. This comprehensive review highlights the oxidative stress interplay with BDNF in AD neuropathology and its potential use as an AD biomarker.

RESUMO O envelhecimento da população representa um sério desafio no que diz respeito ao aumento da prevalência da doença de Alzheimer (DA) e o seu impacto na carga, morbidade e mortalidade globais. O estresse oxidativo, como uma marca molecular que causa suscetibilidade na DA, interage com outras cascatas de neuropatologia relacionadas à DA e diminui a expressão do fator neurotrófico encefálico (brain-derived neurotrophic factor - BDNF), uma neurotrofina essencial que serve como desenvolvimento e sobrevivência nervosa, e plasticidade sináptica na DA. Pela sua correlação significativa com a progressão molecular e clínica da DA, o BDNF pode potencialmente ser usado como um biomarcador objetivamente preciso para o diagnóstico da DA e acompanhamento da progressividade na prática clínica futura. Esta revisão abrangente destacou a interação do estresse oxidativo com o BDNF na neuropatologia da DA e seu uso potencial como biomarcador da DA.

Blood levels of brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE): a systematic review and meta-analysis

Abstract Objectives BDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE. Methods We searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle-Ottawa scale was used to assess the quality of the included publications, and statistical analyses were carried out using R 4.0.4. Results The final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [− 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [− 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R2 were 26.89%, 16.53%, 18.8%, and 49.96%, respectively). Conclusion In conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies.

Effect of Anmeidan on Serum Levels of BDNF， GFAP， and Irisin in Patients with Chronic Insomnia / 中国实验方剂学杂志

ObjectiveTo explore the effect of Anmeidan on the sleep quality and serum levels of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and irisin in the patients with chronic insomnia. MethodA multicenter， randomized， double-blind， placebo-controlled clinical study was carried out， including 480 patients with chronic insomnia （deficiency syndrome） in Wuhan （Hubei）， Guangzhou （Guangdong）， and Lanzhou （Gansu）. They were randomized into an observation group and a control group at a ratio of 1∶1. The observation group was orally administered with Anmeidan granules at a dose of 11 g， 3 times per day， and the control group with Anmeidan simulant at a dose of 11 g， 3 times per day， Both groups of patients received sleep education after enrollment. After 4 weeks of medication， the Athens insomnia scale （AIS） scores， Spiegel scale scores， and serum levels of BDNF， GFAP， and irisin were compared between the two groups as well as between before and after treatment. ResultA total of 480 adult patients with chronic insomnia were enrolled in this study， with 64 patients falled off. Finally， the 415 patients were included in the analysis， including 213 patients in the observation group and 202 patients in the control group. There was no difference in age or sex between the two groups of patients. Compared with before treatment， the treatment in both groups decreased the AIS and Spiegel scores （P<0.01）. After treatment， the observation group had lower AIS and Spiegel scores than the control group （P<0.01）. The treatment in the observation group slightly lowered the level of BDNF， elevated the level of irisin （P<0.05）， and lowered the level of GFAP （P<0.05） in the serum. After treatment， the observation group showed higher level of irisin （P<0.05） and lower levels of BDNF and GFAP in the serum than the control group. ConclusionAnmeidan may improve the sleep quality of patients with chronic insomnia by elevating the irisin level and lowering the GFAP level in the serum.

Puerarin reduces intracellular Ca2+ concentration and upregulates BDNF to protect hippocampal neurons in vascular dementia rats / 西安交通大学学报(医学版)

【Objective】 To observe the effect of puerarin on the concentration of Ca2+ and the expression of brain derived neurotrophic factor (BDNF) in hippocampal neurons of vascular dementia (VD) rats so as to explore the mechanism of puerarin in protecting nerve cells. 【Methods】 Male SD rats were randomly divided into sham operation group, model group, and puerarin intervention group. The vascular dementia model was established by ligating bilateral common carotid arteries at intervals of 3 days. Two weeks after the operation, the learning and memory abilities of the rats were evaluated by Morris water maze, and the expression of BDNF in the hippocampus of the rats was detected by immunohistochemistry and Western blotting. The mean fluorescence intensity was measured by flow cytometry to represent the intracellular free Ca2+ concentration. 【Results】 In the puerarin intervention group, the rats’ escape latency in Morris water maze was significantly shortened, the expression of BDNF in the hippocampus was significantly increased, and the concentration of Ca2+ in hippocampal neurons was decreased. Compared with the model group, the difference was statistically significant (all P<0.05). 【Conclusion】 Puerarin has neuroprotective effect on VD rats, and its mechanism may be related to the decrease of Ca2+ concentration in hippocampal neurons and the up-regulation of BDNF expression.

Ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 for the treatment of primary retinitis pigmentosa / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 on serum brain-derived neurotrophic factor(BDNF), pituitary adenylate cyclase activating polypeptide(PACAP)and clinical efficacy in primary retinitis pigmentosa.METHODS: A total of 50 patients(100 eyes)with primary retinitis pigmentosa who admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Hebei North University from August 2019 to March 2022 were selected as the research object. They were divided into the study group and the control group according to random number table, with 50 eyes in each group. Patients in the control group were treated with inosine tablets and vitamin B1, while patients in the study group were treated with ginsenoside Rg1 injection on the basis of the control group. The expression of BDNF and PACAP in serum, electroretinogram and spectral-domain optical coherence tomography(SD-OCT)were compared before and after treatment, and the retinal thickness(RT), mean deviation(MD), clinical efficacy and safety indexes were compared between the two groups.RESULTS: There were no differences in the MD of the two groups before treatment(t=1.670, P=0.098), while the MD of the study group was significantly lower than that of the control group after treatment(t=3.628, P&#x003C;0.01). Before treatment, RT with a diameter of 1mm at the circle of macular fovea was compared between the two groups(t=0.108, P=0.914), it was significantly higher than that in the control group after treatment(t=6.125, P&#x003C;0.01). Before treatment, there was no significant difference in the results of dark adaptation of electroretinogram between the two groups(all P&#x003E;0.05). After treatment, the results of dark adaptation in the study group were significantly better than those in the control group(all P&#x003C;0.01). Before treatment, there was no significant difference in the results of electroretinogram adaptation between the two groups(all P&#x003E;0.05). After treatment, the results of electroretinogram adaptation in the study group were significantly better than those in the control group(all P&#x003C;0.01). There was no significant difference in BDNF and PACAP between the two groups before treatment(all P&#x003E;0.05). BDNF and PACAP in the study group were higher than those of the control group after treatment(all P&#x003C;0.01). After treatment, no adverse reactions were observed in both groups.CONCLUSION: The treatment of patients with primary retinitis pigmentosa with ginsenoside will improve the retinal function and promote the prognosis of the disease by regulating the expression of BDNF and PACAP, and it is highly safe.

Progress of cyclic adenosine monophosphate responsive element binding protein in the pathogenesis of drug-resistant epilepsy / 中华神经科杂志

Recent studies have found that in the development of epilepsy, cyclic adenosine monophosphate response element binding protein (CREB) may cause recurrent epilepsy by inhibiting the expression of γ-aminobutyric acid, resulting in neuron damage and weakened effect of antiepileptic drug targets. Antiepileptic drugs can not control the extent or frequency of seizures, and then the patients are in a persistent state, hence the development of drug-resistant epilepsy. Therefore, the mechanism of CREB leading to drug-resistant epilepsy was reviewed in this paper, hoping to provide ideas for the treatment of drug-resistant epilepsy patients.

Role of P2X4R in maintenance of trigeminal neuralgia in rats: relationship with p38 MAPK/BDNF signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.

Areca catechu L.ameliorates chronic unpredictable mil stress-induced depression behavior in rats by the promotion of the BDNF signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigated the anti-de-pressant effects of the fruit Areca catechu L.(ACL)and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress(CUMS).METHODS CUMS was induced in rats to establish a depression animal model for 28 d.According to the baseline sucrose preference,the male rats were divided into six different groups.They were treated with parox-etine hydrochloride,ACL,and water once a day until the behavioral tests were performed.The levels of corticoste-rone(CORT),malondialdehyde(MDA),catalase(CAT),and total superoxide dismutase(T-SOD)in serum were de-tected using a commercial kit,and the concentrations of 5-hydroxytryptamine(5-HT)and dopamine(DA)mono-amine neurotransmitters in the brain tissues were detect-ed by liquid chromatography-tandem mass spectrometry.Doublecortin(DCX)expression in the hippocampal den-tate gyrus(DG)was determined by immunofluorescence,and the relative abundance of brain-derived neurotrophic factor(BDNF),TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β of brain tissues were assayed by West-ern blotting.RESULTS ACL markedly increased sucrose preference,decreased the immobility time,and short-ened the feeding latency of CUMS-induced rats.CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters(5-HT and DA)in the hippocampus and cortex of brain tissues and the levels of CORT,MDA,CAT,and T-SOD in serum,whereas ACL administration alleviated these considerable changes.ACL promoted DCX expression in DG and increased the protein levels of BDNF,TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.CONCLUSION Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis,stimulating hippo-campal neurogenesis,and activating the BDNF signaling pathway.

Meta-analysis of the association between brain-derived neurotrophic factor in peripheral blood and Alzheimer's disease / 中华行为医学与脑科学杂志

Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.

Effects of tandospirone combined with venlafaxine on neurotransmitters and related factors in patients with comorbid anxiety and depression / 中国基层医药

Objective:To investigate the efficacy of tandospirone combined with venlafaxine in the treatment of comorbid anxiety and depression and its effects on neurotransmitters and related factors.Methods:A total of 92 patients with comorbid anxiety and depression who received treatment in the Second People's Hospital of Lishui between June 2019 and June 2020 were included in this study. They were randomly divided into an observation group and a control group ( n = 46/group). The control group was treated with venlafaxine, while the observation group was treated with tandospirone and venlafaxine. Before and after treatment, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), the levels of 5-hydroxytryptamine, brain-derived neurotrophic factor, nerve growth factor, and adverse drug reactions were compared between the two groups. Results:At 4 and 8 weeks after treatment, HAMA scores in the observation group were (11.39 ± 3.11) points and (8.26 ± 2.18) points, respectively, which were significantly lower than (14.72 ± 3.57) points and (10.46 ± 2.37) points in the control group ( t = 4.77, 4.63, both P < 0.05). At 4 and 8 weeks after treatment, HAMD scores in the observation group were (15.95 ± 2.90) points and (9.33 ± 1.54) points, respectively, which were significantly lower than (17.43 ± 2.87) points and (13.28 ± 2.65) points in the control group ( t = 2.46, 8.74, both P < 0.05). After treatment, 5-hydroxytryptamine, nerve growth factor, and brain-derived neurotrophic factor levels in the observation group were (154.59 ± 45.26) μg/L, (13.62 ± 1.16) ng/L, (28.54 ± 2.33) ng/L, respectively, which were significantly higher than (129.99 ± 48.31) μg/L, (11.98 ± 1.04) ng/L, and (25.69 ± 2.51) ng/L in the control group ( t = 2.52, 7.14, 5.64, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( χ2 = 0.81, P = 0.369). Conclusion:The adjuvant treatment with tandospirone can markedly improve anxiety and depression and protect neurological function of patients with comorbid anxiety and depression, and is highly safe.

Validation of the Brazilian version of the child pain catastrophizing scale and its relationship with a marker of central sensitization

Abstract Objectives The Pain Catastrophizing Scale-Child version (PCS-C) allows to identify children who are prone to catastrophic thinking. We aimed to adapt the Brazilian version of PCS-C (BPCS-C) to examine scale psychometric properties and factorial structure in children with and without chronic pain. Also, we assessed its correlation with salivary levels of Brain-Derived Neurotrophic factor (BDNF). Methods The Brazilian version of PCS-C was modified to adjust it for 7-12 years old children. To assess psychometric properties, 100 children (44 with chronic pain from a tertiary hospital and 56 healthy children from a public school) answered the BPCS-C, the visual analogue pain scale, and questions about pain interference in daily activities. We also collected a salivary sample to measure BDNF. Results We observed good internal consistency (Cronbach's value = 0.81). Parallel analysis retained 2 factors. Confirmatory factor analysis of our 2-factor model revealed consistent goodness-of-fit (IFI = 0.946) when compared to other models. There was no correlation between visual analogue pain scale and the total BPCS-C score; however, there was an association between pain catastrophizing and difficulty in doing physical activities in school (p= 0.01). BPCS-C total scores were not different between groups. We found a marginal association with BPCS-C (r= 0.27, p= 0.01) and salivary BDNF levels. Discussion BPCS-C is a valid instrument with consistent psychometric properties. The revised 2-dimension proposed can be used for this population. Children catastrophism is well correlated with physical limitation, but the absence of BPCS-C score differences between groups highlights the necessity of a better understanding about catastrophic thinking in children.

Effect of providing purple sweet potato water extract on tumor necrosis factor-α levels, protein 53 expression, glial fibrillary acidic protein expression, brain-derived neurotrophic factor levels, and spatial working memory in rats with d-galactose induction / Efeito do extrato de água de batata doce roxo no fator de necrose tumoral níveis alfa, na expressão da proteína 53, na expressão de proteína ácida fibrilar glial, nos níveis de fator neurotrófico cerebral e na memória espacial em ratos com indução de d-galactose

ABSTRACT. Alzheimer's dementia (AD) is a neurodegenerative disease. The mechanism of oxidative stress in AD is due to amyloid beta (Aβ) protein that aggregates to form plaques, which further triggers chronic inflammation and neuronal apoptosis. Purple sweet potato extract with the main content of anthocyanins is a potential antioxidant with a direct target on the amyloid cascade hypothesis. Objective: The research objective was to determine the role of purple sweet potato water extract as an antioxidant and anti-inflammatory in preventing apoptosis in order to provide a neuroprotective effect in d-galactose-induced rats. Methods: A total of 100 male Wistar rats with randomized posttest-only control group design that met the eligibility criteria were included in this study. The treatment group was given 200 mg/kg BW/day of purple sweet potato water extract on days 1-70. d-galactose induction was administered in the treatment and control groups on days 15-70. Results: The independent t-test showed that the mean tumor necrosis factor-α (TNF-α) levels in the treatment group (735.36±139.74) was significantly lower than that in the control group (896.77±152.52). The p53 and glial fibrillary acidic protein (GFAP) expressions of astrocyte cells in the treatment group were significantly lower than that in the control group. The brain-derived neurotrophic factor (BDNF) levels in the treatment group (498.13±121.47) were higher than that in the control (391.93±140.28), and there was a significant increase in spatial working memory in the treatment group (72.01±10.22) than the control (59.77±11.87). Conclusions: The neuroprotective effect of purple sweet potato extract is due to d-galactose induction resulting from decrease in TNF-α levels, p53 expression, and GFAP expression and increase in BDNF levels and spatial working memory.

RESUMO. A doença de Alzheimer (DA) é uma doença neurodegenerativa. O mecanismo de estresse oxidativo na DA ocorre devido à proteína beta amilóide que se agrega para formar placas que desencadeiam inflamação crônica e apoptose neuronal. O extrato de batata-doce roxa composto principalmente por antocianinas é um potencial antioxidante com efeito direto sobre a hipótese da cascata amilóide. Objetivo: O objetivo da pesquisa foi determinar o papel do extrato aquoso de batata-doce roxa como antioxidante e anti-inflamatório na prevenção da apoptose, para proporcionar um efeito neuroprotetor em ratos induzidos por D-galactose. Métodos: Grupo controle randomizado pós-teste com 100 ratos Wistar machos que preencheram os critérios de elegibilidade. O grupo de tratamento recebeu 200mg/kg de peso corporal/dia de extrato aquoso de batata-doce roxa nos dias 1-70. A indução de D-galactose foi testada nos grupos de tratamento e controle nos dias 15-70. Resultados: O teste t independente mostrou que a média dos níveis de TNF-α no grupo de tratamento (735,36±139,74) foi significativamente menor do que no grupo controle (896,77±152,52). A expressão de p53 e a expressão de GFAP de células de astrócitos foram significativamente menores no grupo de tratamento do que no grupo controle. Os níveis de BDNF no grupo de tratamento (498,13±121,47) foram maiores que no grupo controle (391,93±140,28) e houve um aumento significativo da memória de trabalho espacial no grupo de tratamento (72,01±10,22) em relação ao controle (59,77±11,87). Conclusões: O efeito neuroprotetor do extrato de batata-doce roxa é devido à indução de D-galactose pela diminuição dos níveis de TNF-α, expressão de p53 e expressão de GFAP, aumentando assim os níveis de BDNF e memória espacial.

Protective effects of melatonin in cisplatin-induced cardiac toxicity: possible role of BDNF-TNF-α signaling pathway

Purpose: The present study explored the role of melatonin in cisplatin-induced cardiac injury along with the possible role of brain-derived neurotrophic factor (BDNF) in melatonin-mediated effects. Methods: Wistar rats were administered cisplatin (10 mg/kg), and cardiac injury was assessed by measuring the levels of cardiac troponin (cTnT) and lactate dehydrogenase (LDH-1).The extent of apoptosis was measured by measuring caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic) in hearts. The levels of BDNF, tumour necrosis factor α (TNF-α) and reduced glutathione were measured in heart. Melatonin (5 and 10 mg/kg) was administered for 15 days, and the role of BDNF was identified by co-administering BDNF inhibitor, ANA-12 (0.25 and 0.5 mg/kg). Results: Melatonin attenuated cTnT and LDH-1 levels along with reduction in caspase-3 and increase in Bcl-2. It also increased cisplatin-induced decrease in BDNF, increase in TNF-α and decrease in reduced glutathione levels. Moreover, ANA-12 abolished the cardioprotective effects, anti-inflammatory and antioxidant effects of melatonin suggesting the role of BDNF in melatonin-mediated effects in cisplatin-induced cardiac injury. Conclusions: Melatonin is useful in cisplatin-induced cardiac injury, which may be due to an increase in BDNF, decrease in inflammation and increase in antioxidant activities.

Efficacy of neuroendoscopic hematoma removal versus soft channel drainage for chronic subdural hematoma / 中国基层医药

Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma (CSDH) and their effects on neurological function and quality of life. Methods:The clinical data of 97 patients with CSDH who received treatment between February 2018 and December 2019 were retrospectively analyzed. These patients were divided into group A ( n = 48, soft channel drainage) and group B ( n = 49, neuroendoscopic hematoma removal) according to different surgical methods. Clinical indicators, neurological function, quality of life, and incidence of complications were compared between groups A and B. Results:Operative time, length of hospital stay, and latency to hematoma disappearance in group B were (31.3 ± 2.18) minutes, (8.16 ± 1.32) days, (7.45 ± 1.49) days, which were significantly shorter than those in group A [(35.15 ± 4.32) minutes, (13.18 ± 1.56) days, (11.32 ± 1.88) days, t = 5.53, 17.12, 11.25, all P < 0.001]. At 3 months after surgery, the score of each dimension of SF-36 in each group was increased. The scores of physiological functioning, bodily pain, mental health, general health perceptions, social role functioning, vitality, role limitations due to emotional health, role limitations due to physical health in group B were (84.94 ± 7.25) points, (84.02 ± 6.29) points, (82.85 ± 8.16) points, (84.36 ± 9.15) points, (83.51 ± 10.39) points, (82.68 ± 8.36) points, (84.93 ± 10.15) points, (86.12 ± 9.13) points, which were significantly higher than those in group A [(62.68 ± 5.47) points, (71.39 ± 7.42) points, (69.51 ± 6.39) points, (72.68 ± 7.36) points, (72.81 ± 8.15) points, (73.12 ± 10.13) points, (77.91 ± 9.52) points, (75.32 ± 7.51) points, t = 19.82, 18.34, 19.75, 16.71, 17.94, 20.57, 18.22, 16.44, all P < 0.001]. At 7 days after surgery, neurotrophic factor, neuron specific enolase, hydrogen sulfide and S100B protein levels in group B were (42.53 ± 6.09) μg/L, (6.52 ± 2.79) μg/L, (203.17 ± 15.03) μmol/L, (0.25 ± 0.05) μg/L, respectively, which were significantly lower than those in group A [(67.38 ± 7.42) μg/L, (9.18 ± 2.27) μg/L, (242.79 ± 14.08) μmol/L, (0.36 ± 0.07) μg/L, t = 17.94, 5.12, 13.33, 8.86, all P < 0.001]. There was no significant difference in the incidence of complications between group B and group A [8.16% (4/49) vs. 18.75% (9/48), χ2 = 2.22, P = 0.136]. Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can better improve clinical indicators, neurological function, and quality of life in patients with CSDH, and is highly safe Neuroendoscopic hematoma removal is of certain clinical application value and innovation.

Effects of aluminum on expressions of fat mass and obesity-associated protein and brain-derived neurotrophic factor in rat brain and PC12 cells / 环境与职业医学

Background Chemical modification of RNA is a recent hotspot in the field of epigenetics, but the specific mechanism of chemical modification of RNA in aluminum neurotoxicity has not been fully reported. Objective To investigate the alterations of fat mass and obesity-associated protein (FTO), that demethylates N6-methyladenosine (m6A), and brain-derived neurotrophic factor (BDNF) in different brain regions of rats and rat adrenal pheochromocytoma differentiated cells (PC12 cells) following aluminum exposure. Methods Animal experiment: Twenty-four healthy male SD rats were randomly divided into a control group (normal saline) and 10, 20, and 40 μmol·kg−1 exposure groups according to body weight, with 6 rats in each group. Maltol aluminum [Al(mal)3] was injected intraperitoneally every other day for 3 months. Cell experiment: PC12 cells were divided into a control group and 100, 200, and 400 μmol·L−1 exposure groups exposed to Al(mal)3 for 24 h. After exposure, the learning and memory ability of rats was measured by water maze experiment, and the protein expression levels of FTO and BDNF in rat cortex (n=6) and hippocampus (n=6) samples as well as in PC12 cells (n=5) were determined by Western blotting. Results The results of water maze test showed that the escape latency of the 40 μmol·kg−1Al(mal)3 group was higher than those of the control group, the 10 μmol·kg−1Al(mal)3 group, and the 20 μmol·kg−1Al(mal)3 group on day 3, 4, and 5 of training (P<0.05). The retention time of the target quadrant of the 40 μmol·kg−1Al(mal)3 group was also reduced compared with that of the control group (P<0.05), indicating that aluminum exposure damaged the learning and memory ability of the rats. The Western blotting results showed that in the cortex, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05). In the hippocampus, compared with the control group, the protein expression levels of FTO and BDNF in the 20 μmol·kg−1 and the 40 μmol·kg−1Al(mal)3 groups were decreased (P<0.05). In PC12 cells, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05). Conclusion Aluminum-induced learning and memory impairment is related to a simultaneous reduction of FTO and BDNF protein expressions, suggesting that m6A methylation may be involved.