Expression Levels Of BDNF Research Articles

Lipidomics Analysis Reveals the Effects of Docosahexaenoic Acid from Different Sources on Prefrontal-Cortex Synaptic Plasticity

Background: Docosahexaenoic Acid (DHA) is an extensively used nutrition supplement in dairy food because of its beneficial effects on cognition. To find an effective DHA intervention for the synapses in the cortex during this period, this study aimed to use targeted lipidomics to evaluate the lipid composition of prefrontal-cortex (PFC) tissue in different DHA interference methods. Methods: Analyzed samples were taken from interfering feeding Bama pigs (BPs) (3 months) fed with soybean oil (Group B), blended oil (Group M), naturally DHA-supplemented milk with blended oil (Group OM), and DHA from fish oil (FO) with blended oil (Group Y). We also examined the protein expression levels of BDNF, GAP43, and MBP. Results: The lipidomics analysis identified 80 different related negative-ion lipid content and filtered the biomarker lipids in PFC tissue. We observed significant lipid composition changes between group Y and other groups, especially for content levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM). The same observations were made from mRNA and protein expressions related to lipid transportation, phosphatidylserine (PS) synthetase, and synaptic plasticity in PFC tissues between group Y and other groups, including the mRNA expression levels of CD36, BDNF, and PTDSS1. The analysis of protein expression levels showed that the metabolism mode of DHA intervention from FO benefited the PFC, PS metabolism, and PFC synaptic plasticity of infants. Conclusions: The results highlight further prospects for the DHA intervention mode, which provides new routes for other studies on polyunsaturated-fatty-acid (PUFA) interference for infants.

The Role of SIRT1-BDNF Signaling Pathway in Fluoride-Induced Toxicity for Glial BV-2 Cells.

Chronic fluorosis is often accompanied by neurological symptoms, leading to attention, memory and learning ability decline and causing tension, anxiety, depression, and other mental symptoms. In the present study, we analyzed the molecular mechanisms of SIRT1-BDNF regulation of PI3K-AKT, MAPK, and FOXO1A in F-treated BV2 cells. The cytotoxic effect of sodium fluoride (NaF) on BV2 cells was assessed using Cell Counting Kit-8 (CCK-8), crystal violet, and 5-ethynyl-2'-deoxyuridine (EdU) staining. Cell cycle progression and apoptosis were evaluated through flow cytometry and western blotting. Reactive oxygen species (ROS) levels, oxidative stress, and inflammatory markers were measured by ROS staining, microplate reader assays, and western blotting. The role of SIRT1 in fluoride-induced toxicity for glial cells was determined using the SIRT1 activator SRT1720. The experiments demonstrated that NaF was toxic to BV2 cells, inhibited their proliferative ability, halted their cell cycle progression, triggered cellular apoptosis, promoted cellular oxidative stress (detected by ROS, SOD, MDA, GSH-Px, T-AOC) and associated protein NQO-1 and HO-1, and elevated inflammatory mediator associated protein IL-1and IL-6 expression). The fluoride-exposed groups had reduced SIRT1, BDNF, TrkB, PI3K, AKT, and MAPK protein expression levels, and increased FOXO1A protein expression. SRT1720 mitigated the harmful effects of NaF, stimulated cell proliferation and cell cycle progression, decreased apoptosis, reduced oxidative stress and inflammatory factors, elevated SIRT1, BDNF, TrkB, PI3K, AKT, and MAPK protein levels, and suppressed FOXO1A protein expression. The results indicate that NaF potentially harms glial cells by suppressing SIRT1 activation, and SIRT1 significantly mitigated the damage. Furthermore, the SIRT1 signaling pathway might regulate the nerve damage caused by fluoride poisoning and may be a protective factor in treating fluoride-induced brain injury.

Syringa oblata Lindl extract alleviated corticosterone-induced depression via the cAMP/PKA-CREB-BDNF pathway.

Syringa oblata Lindl (ZDX) is a plant in the Oleaceae family that is the primary ingredient in the classic Tibetan medicine AKARU sinensis. The plant's stem is used as a medicine, and Tibetan doctors often use it as a sedative, a use with a history of nearly 100 years. Tibetan medicine mainly uses lilac to treat headache, forgetfulness, insomnia, irritability and other symptoms. Depression is a chronic mental disorder characterized by low mood, cognitive impairments, and physical discomfort, and it has become a significant public health issue. Given the limitations of existing treatments, interest in alternative therapies, including herbal medicines, is increasing. To elucidate the mechanism of ZDX extract in the treatment of depression. A depression-like mouse model was established via the subcutaneous injection of corticosterone (CORT) into the groin, and a model of PC12cell injury was established via CORT treatment. The antidepressant effect of the ZDX extract was subsequently evaluated via weight measurements, the sucrose preference test (SPT), the forced swimming test (FST), the open field test(OFT), the tail suspension test (TST), HE staining, Nissl staining and ELISA. Moreover, immunofluorescence staining, qRT‒PCR and Western blotting were used to determine whether ZDX extract can regulate the cAMP/PKA-CREB-BDNF pathway to prevent depression and neuronal apoptosis. ZDX extract significantly improved depression-like behaviours; inhibited decreases in the protein levels of cAMP, PKA, CREB and BDNF; and increased proliferative activity in the hippocampus and cortex. In addition, in vitro, ZDX extract attenuated CORT-induced injury and apoptosis in hippocampal neurons and inhibited CORT-induced decreases in the mRNA expression levels of cAMP, PKA, CREB and BDNF. These findings suggest that ZDX extract has potential as a novel antidepressant therapeutic agent, offering a complementary approach to current treatments by targeting multiple pathways involved in the pathogenesis of depression. Further research is warranted to explore the clinical applications of ZDX extract in the treatment of depression.

Experimental study on the effect of Mongolian medicine warming acupuncture on proBDNF-tPA-BDNF balance in depression rats based on thermal imaging monitoring

Depression is a kind of mental illness affecting the whole world. Its pathological mechanism is complex, involving neurobiological and psychosocial factors.The depression model rats were randomly divided into control group, warm acupuncture group and drug treatment group. In order to evaluate the local thermal effect of warm acupuncture and moxibustion, real-time temperature changes of rat forebrain were monitored by thermal imaging technology. After the experiment, immunohistochemistry and Western blot were used to detect the expression levels of tPA and BDNF in the forebrain of each group of rats, and the relationship between tPA and BDNF was analyzed. The results of thermal imaging monitoring showed that local forebrain temperature in warm acupuncture group was significantly increased compared with control group (p < 0.05). The ratio of tPA to BDNF was significantly improved in the warm acupuncture and moxibustion group, suggesting that warm acupuncture and moxibustion can effectively regulate the balance of TPA-BDNF. The experimental results based on thermal imaging monitoring suggest that warm acupuncture can improve the balance of TPA-BDNF in the forebrain of depressed rats by promoting the expression of BDNF and tPA in the forebrain, which may provide a new method and mechanism basis for the treatment of depression.

Euonymus hamiltonianus Extract Improves Amnesia in APPswe/Tau Transgenic and Scopolamine-Induced Dementia Models.

Dementia is a syndrome exhibiting progressive impairments on cognition and behavior beyond the normal course of aging, and Alzheimer's disease (AD) is one of the neurodegenerative diseases known to cause dementia. We investigated the effect of KGC07EH, the 30% ethanol extract of Euonymus hamiltonianus, against amyloid-β (Aβ) production and cognitive dysfunction in dementia models. KGC07EH was treated on Hela cells expressing the Swedish mutant form of amyloid precursor protein (APP), and the AD triple transgenic (3× TG) mice were given KGC07EH orally during 11-14 months of age (100 and 300mg/kg/day). SH-SY5Y cell line was used to test KGC07EH on scopolamine-induced elevation of acetylcholinesterase (AChE) activity. ICR mice were intraperitoneally injected with scopolamine, and KGC07EH was administered orally (50, 100, and 200mg/kg/day) for 4 weeks. KGC07EH treatment decreased Aβ, sAPPβ-sw, and sAPPβ-wt levels and APP protein expressions while sAPPα was increased in Swedish mutant-transfected HeLa cells. KGC07EH treatment also significantly reduced the accumulation of Aβ plaques and tau tangles in the brain of 3× TG mice as well as improving the cognitive function. In SH-SY5Y cells cultured with scopolamine, KGC07EH dose-dependently attenuated the increase of AChE activity. KGC07EH also improved scopolamine-induced learning and memory impairment in scopolamine-injected mice, and in their cerebral cortex and hippocampus, the expression levels of p-ERK, p-CREB, p-Akt, and BDNF were attenuated. KGC07EH inhibits APP processing and Aβ production both in vitro and in vivo, while enhancing acetylcholine signaling and cognitive dysfunction which are the major symptoms of dementia.

The combined use of thymoquinone and metformin provides more effective neuroprotection in a mouse model of MPTP-induced Parkinson’s disease

Thymoquinone (TQ) is known for its antioxidant properties, and although metformin (MM) is known as an antidiabetic drug, it is suggested that it reduces neurodegeneration. The study aimed to investigate the neuroprotective effects of TQ and MM, particularly when used together, in relation to Parkinson’s disease (PD). In the study, sixty-eight male C57BL/6 mice weighing 25–30 g were divided into five groups as follows: control, MPTP, MPTP+TQ, MPTP+MM, and MPTP+TQ+MM. MM (500 mg/kg, orally) and TQ (5 mg/kg, i.p.) were administered for 21 days. Motor coordination and locomotor activities were evaluated by the pole test. TOS and TAS analyses were conducted to determine oxidative stress levels in the substantia nigra. Dopaminergic degeneration in the substantia nigra was evaluated by analyzing Tyrosine hydroxylase (TH). To evaluate the apoptotic pathway, the expression levels of iNOS, BDNF, Complex 1, Bax, Bcl-2, Cytochrome C, AIF, and Caspase-3 were examined immunohistochemically. Compared to the MPTP-treated group, TQ, MM and MM+TQ treatment provided significant improvement in locomotor activity in mice, significantly increased antioxidant activity, significantly reduced the expression levels of iNOS, Bax, Cytochrome C, Caspase-3, and AIF, significantly increased BDNF, Bcl-2, and Complex 1 expressions, and significantly increased the number of TH positive cells. The separate use of TQ and MM exhibits neuroprotective activity, however, we showed that using TQ and MM in combination may be more effective. This may provide preclinical evidence supporting the therapeutic potential of their combined use for treating PD.

Associations between methamphetamine use disorder and SLC18A1, SLC18A2, BDNF, and FAAH gene sequence variants and expression levels.

Assessing candidate gene sequence variations and expression helps to understand methamphetamine use disorder and inform potential treatments. We investigated single nucleotide polymorphisms (SNPs) and gene expression in four candidate genes: SLC18A1, SLC18A2, BDNF, and FAAH, between controls and people with methamphetamine use disorder. Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. SLC18A1, SLC18A2, BDNF, and FAAH SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR. SLC18A1 Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; p = .007). SLC18A2 variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity (p = .003) and positively associated with inhibitory control performance (p = .006), respectively. BDNF Val66Met was associated with the severity of use (p = .008). SLC18A2 and FAAH mRNA levels were lower in people who use methamphetamine relative to controls (p = .021 and .010, respectively). SLC18A1 is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood SLC18A2 and FAAH mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release, and higher anandamide levels in this clinical group, which may be potential therapeutic targets.

Saroglitazar, a PPAR α/γ agonist alleviates 3-Nitropropionic acid induced neurotoxicity in rats: Unveiling the underlying mechanisms

Saroglitazar (SGZ), a peroxisomal proliferated activated receptor α/γ agonist showed neuroprotective effects in various neurodegenerative disorders like Alzheimer’s and Parkinson’s. However, no studies were performed on Huntington’s, so the goal of the current study is to examine the effect of SGZ on Huntington’s disease like symptoms induced by 3-Nitropropionic acid. In this protocol, twenty-four rats were divided into four groups, each group consisting of 6 animals. Group 1: The control group received 1 % CMC 10 mg/kg, p.o. for 14 days. Groups 2, 3, and 4 received 3-NP 15 mg/kg, i.p. from Day 1 to Day 7. Groups 3 and 4 received SGZ 5 mg/kg, p.o. and 10 mg/kg, p.o. respectively once daily from day 1 to day 14. Various behavioral tests like OFT, rotarod, hanging wire, narrow beam walk, MWM, and Y-maze were performed. On day-15, the animals were euthanised by cervical dislocation and brain sample were isolated for biochemical and histopathological analysis. Administration of 3-NP showed a significant decrease in motor coordination and cognitive function. Furthermore, 3-NP altered the activity of acetylcholinesterase, anti-oxidant enzymes, Nrf-2, NF-κB, BDNF, CREB levels, and histological features. However, treatment with SGZ showed ameliorative effects in the 3-NP induced neurotoxicity via PPAR α/γ pathway by reducing motor dysfunction, memory impairment, cholinesterase levels, oxidative stress, neuroinflammation. It also enhanced the levels of Nrf-2, BDNF, and CREB expression and improved histological features. In conclusion, treatment with Saroglitazar attenuated Huntington’s disease-like symptoms in rats which are induced by 3-NP via activation of PPAR α/γ pathway.

Investigating the influence of estrous cycle-dependent hormonal changes on neurogenesis in adult mice

ObjectiveNeurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult brain. Sex hormones play an essential role in the development of the brain. The aim of this study was to evaluate the neurogenic changes in the brain at different phases of the estrous cycle in adult mice. Materials and methodsFemale NMRI mice were divided into four groups: 1- Estrous, 2- Proestrous, 3- Metestrous, and 4- Diestrous. Different stages of the estrous cycle were determined by staining of vaginal smears. The level of estrogen, progesterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones was evaluated by the enzyme-linked immunosorbent assay (ELISA) method. The expression of brain-derived neurotrophic factor) BDNF), nerve growth factor (NGF), ciliary neurotrophic factor(CNTF)) genes in hippocampal and the expression of glial fibrillary acidic protein (GFAP) in subventricular zone (SVZ) tissue were evaluated. ResultsThe serum estrogen and FSH increased significantly in Proestrous group (p < 0.001). Also, progesterone and prolactin hormones were significantly increased in the Diaestrus group (p < 0.001). The expression levels of BDNF, NGF, and CNTF significantly increased in the hippocampal tissue of Proestrous and Diaestrus groups (p < 0.001). The number of GFAP+ cells in SVZ of the Proestrous and Diestrous groups had a significant increase (p < 0.05, p < 0.01, p < 0.001). ConclusionOur data showed that Changes in sex hormones, especially estrogen in the estrous cycle, can cause the production of new neurons and astrocytes in the hippocampus and SVZ. Therefore, the increase in neurotrophic factors in the Proestrus and Diestrus leads to neurogenesis in adult mice brains.

Involvement of &lt;i&gt;Bdnf&lt;/i&gt;, &lt;i&gt;Ntrk2&lt;/i&gt; and &lt;i&gt;Pi3k&lt;/i&gt; in the mechanism of binge eating after psychogenic stressors in ontogenesis

BACKGROUND: The study of the neurochemical mechanisms of food addiction provides experimental modeling of some of its clinical manifestations. AIM: This study aimed to examine the effect of binge eating after maternal deprivation or after rearing in social isolation on the expression of Bdnf, Ntrk2, and Pi3k in the hypothalamus of rats. MATERIALS AND METHODS: Animals aged 2–12 days were weaned from their mother for 10 days at 180 min, and males aged 90–100 days were used in the experiments. Another group of animals was reared in individual cages from day 21 after birth, and males aged 90–100 days were used in the experiments. To induce binge eating, the animals received a high-carbohydrate feed (chocolate spread) for 1 h every day or every third day within 30 days. Fifteen minutes before feeding, the paste was placed 5 cm within visual contact. RESULTS: In groups with intermittent exposure to high-calorie food (the animals received pasta every third day), polymerase chain reaction analysis revealed the expression of the Bdnf, Ntrk2, and Pi3k in the hypothalamus. The expression level of Bdnf was higher in the maternal deprivation group than in the control group. The expression levels of Ntrk2 and Pi3k in rats taking a high-carbohydrate feed were higher in animals reared in isolation than in those reared in the community. CONCLUSIONS: The results present new pathways for the synthesis of peptide drugs associated with the PI3K/AKT/mTOR signaling pathway for the correction of food addiction caused by psychogenic stress in ontogenesis.

Huanglian Wendan Decoction Improves Insomnia in Rats by Regulating BDNF/TrkB Signaling Pathway Through Gut Microbiota-Mediated SCFAs and Affecting Microglia Polarization.

Insomnia is a typical type of sleep disorder. Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) with the effects of regulating Qi, drying dampness and resolving phlegm, calming the mind, and relieving irritation. This study aims to investigate the effect of HWD on insomnia in rats and its mechanism. Para-chlorophenylalanine (PCPA)-induced insomnia in rats was used for in vivo experiments and then treated with HWD. Behavioral tests, Western blot, real-time PCR, immunofluorescent staining, 16S rRNA sequencing were conducted. The content of SCFAs was determined by GC-MS. Acetic acid-pretreated rat hippocampal nerve cells were used for in vitro experiments. The results showed that HWD significantly improved the learning memory ability, decreased sleep latency, and prolonged sleep duration in insomniac rats. HWD reduced TNF-α and IL-6 levels and increased IL-10 and Foxp3 levels. HWD also promoted the polarization of macrophages from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. In addition, HWD increased the expression levels of BDNF and TrkB in the hippocampus. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone (7,8-DHF) confirmed the mechanism by which HWD activates BDNF/TrkB signaling to ameliorate insomnia. Furthermore, HWD restored gut microbiota richness and diversity and promoted short-chain fatty acid (SCFA) production in insomniac rats. In vitro experiments confirmed that the acetic acid-treated SCFA group could activate the BDNF/TrkB signaling pathway in neuronal cells, further promoting neuronal cell growth. In conclusion, HWD alleviated insomnia by maintaining gut microbiota homeostasis, promoting SCFA production, reducing neuroinflammatory response and microglia activation, and activating BDNF/TrkB signaling pathway.

MiR-204-5p Plays a Critical Role in the Pathogenesis of Depression and Anti-depression Action of Venlafaxine in the Hippocampus of Mice.

Venlafaxine has been demonstrated to treat diseases such as social anxiety disorder and depression. Most of antidepressants including venlafaxine have a certain effect, but significant side effects. Therefore, it is necessary for us to research the development of novel antidepressants for effective treatment in practice. MicroRNA-204 (miR-204) is highly expressed in brain tissue, and plays a critical role in the synaptic plasticity of hippocampal neurons in rats. However, the underlying molecular mechanism of miR-204 remains unclear to date, this study aims to offer unique insights into depression and provide a theoretical basis for clinical physicians. A chronic social defeat stress (CSDS) was initially adopted for establishing a mice model of depression in this research and depression-like behaviors were evaluated by a series of behavioral experiments including the sucrose preference test (SPT), the tail suspension test (TST), the forced swim test (FST) and the social interaction test (SIT). Quantitative real-time reverse transcription PCR (qRT-PCR) was also conducted to test the expression levels of miR-204 and BDNF in the hippocampus of mice. Finally, gene interference of miR-204-5p was further adopted to test whether miR-204-5p played an effective role in the antidepressant effects of venlafaxine in mice. Our data implicated that CSDS significantly increased the miR-204-5p but not miR-204-3p levels in the hippocampus of mice. The treatment of venlafaxine obviously relieved depression- like behaviors of CSDS-induced mice. The usage of venlafaxine abolished the increasing effects on the expression of miR-204-5p but up-regulated the BDNF expression level in CSDS-exposured mice. More importantly, we found that genetic overexpression of miR-204-5p decreased the reverse effects of venlafaxine on depressive-like behaviors and genetic knockdown of hippocampal miR-204-5p relieved the depressive-like behaviors and neurogenesis in CSDS-induced mice. miR-204-5p played an effective role in the antidepressant effects of venlafaxine in CSDS-induced mice.

SEP-363856 exerts neuroprotection through the PI3K/AKT/GSK-3β signaling pathway in a dual-hit neurodevelopmental model of schizophrenia-like mice.

Schizophrenia (SZ) is a serious, destructive neurodevelopmental disorder. Antipsychotic medications are the primary therapy approach for this illness, but it's important to pay attention to the adverse effects as well. Clinical studies for SZ are currently in phase ΙΙΙ for SEP-363856 (SEP-856)-a new antipsychotic that doesn't work on dopamine D2 receptors. However, the underlying action mechanism of SEP-856 remains unknown. This study aimed to evaluate the impact and underlying mechanisms of SEP-856 on SZ-like behavior in a perinatal MK-801 treatment combined with social isolation from the weaning to adulthood model (MK-SI). First, we created an animal model that resembles SZ that combines the perinatal MK-801 with social isolation from weaning to adulthood. Then, different classical behavioral tests were used to evaluate the antipsychotic properties of SEP-856. The levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β), apoptosis-related genes (Bax and Bcl-2), and synaptic plasticity-related genes (brain-derived neurotrophic factor [BDNF] and PSD-95) in the hippocampus were analyzed by quantitative real-time PCR. Hematoxylin and eosin staining were used to observe the morphology of neurons in the hippocampal DG subregions. Western blot was performed to detect the protein expression levels of BDNF, PSD-95, Bax, Bcl-2, PI3K, p-PI3K, AKT, p-AKT, GSK-3β, p-GSK-3β in the hippocampus. MK-SI neurodevelopmental disease model studies have shown that compared with sham group, MK-SI group exhibit higher levels of autonomic activity, stereotyped behaviors, withdrawal from social interactions, dysregulated sensorimotor gating, and impaired recognition and spatial memory. These findings imply that the MK-SI model can mimic symptoms similar to those of SZ. Compared with the MK-SI model, high doses of SEP-856 all significantly reduced increased activity, improved social interaction, reduced stereotyping behavior, reversed sensorimotor gating dysregulation, and improved recognition memory and spatial memory impairment in MK-SI mice. In addition, SEP-856 can reduce the release of proinflammatory factors in the MK-SI model, promote the expression of BDNF and PSD-95 in the hippocampus, correct the Bax/Bcl-2 imbalance, turn on the PI3K/AKT/GSK-3β signaling pathway, and ultimately help the MK-SI mice's behavioral abnormalities. SEP-856 may play an antipsychotic role in MK-SI "dual-hit" model-induced SZ-like behavior mice by promoting synaptic plasticity recovery, decreasing death of hippocampal neurons, lowering the production of pro-inflammatory substances in the hippocampal region, and subsequently initiating the PI3K/AKT/GSK-3β signaling cascade.

Antidepressant effects of activation of infralimbic cortex via upregulation of BDNF and β-catenin in an estradiol withdrawal model

RationaleClinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear.ObjectivesThis study was to observe the antidepressant effect and expression of BDNF and β-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD.MethodsAdministration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of β-catenin and BDNF were observed by western blotting.ResultsImmobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or β-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and β-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats.ConclusionsOur results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and β-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD.

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

Protective Effect of Hop Ethyl Acetate Extract on Corticosterone-Induced PC12 and Improvement of Depression-like Behavior in Mice.

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.

Comparative Analysis of the Sedative and Hypnotic Effects among Various Parts of Zizyphus spinosus Hu and Their Chemical Analysis.

Zizyphus spinosus Hu (ZS), as a "medicinal and food-homologous" plant, has been used for a long history. The study was to assess the sedative and hypnotic effects among various parts of ZS. The model, diazepam (DZP), ZS kernel (ZSS), ZS flesh (ZSF), and ZS husk (ZSKS) group occurred subsequent to the successful establishment of the para-chlorophenylalanine induced insomnia model via intraperitoneal injection. The latency and duration of sleep in mice in each group were recorded. The substance basis of various parts of ZS was analyzed by the UPLC-QTOF-MS technique. The results showed that relative to the model group, DZP, ZSS, ZSF, and ZSKS groups demonstrated shortened sleep latency (p < 0.05) and extended sleep duration (p < 0.01). The GABA, 5-HT, and BDNF levels were significantly upregulated in the brain tissues of the mice in the DZP, ZSF, and ZSS groups (p < 0.01). However, the improvement in ZSKS was non-significant. Additionally, the mRNA and protein expression levels of 5-HT1AR, GABAARα1, and BDNF in mice in the DZP, ZSS, and ZSF groups were significantly enhanced (p < 0.01). However, the improvement in the ZSKS group was insignificant (p < 0.05). The examination of the substance composition across different parts revealed that the shared chemical basis contributing to the sedative and hypnotic potency of different parts of ZS may involve the presence of compounds such as (1) magnoflorine, (8) betulinic acid, (9) ceanothic acid, and (10) alphitolic acid. It provides a basis for further elucidation of the substance basis responsible for the functional and medicinal effects of ZS.

Antidepressant-like effects of hyperoside on chronic stress-induced depressive-like behaviors in mice: Gut microbiota and short-chain fatty acids

BackgroundThe antidepressant effect of hyperoside (HYP), which is the main component of Hypericum perforatum, is not established. This study aimed to determine the effects of HYP on depression. MethodsThe antidepressant-like effect of HYP was studied in mice induced by chronic restraint stress (CRS). The effects of HYP on behavior, inflammation, neurotransmitters, gut microbiota, and short-chain fatty acids (SCFAs) were studied in CRS mice. ResultsHYP improved depressive-like behavior in mice induced by CRS. Nissl staining analysis showed that HYP improved neuronal damage in CRS mice. Western blot (WB) analysis showed that HYP increased the expression levels of BDNF and PSD95 in the hippocampus of CRS mice. The results of ELISA showed that HYP down-regulated the expression levels of IL-6, IL-1β, TNF-α, and CORT in the hippocampus, blood, and intestinal tissues of mice and up-regulated the expression levels of 5-HT and BDNF. Hematoxylin and eosin (HE) staining results indicate that HYP can improve the intestinal histopathological injury of CRS mice. The results of 16S rRNA demonstrated that HYP attenuated the dysbiosis of the gut microbiota of depressed mice, along with altering the concentration of SCFAs. LimitationsIn the present study, direct evidence that HYP improves depressive behaviors via gut microbiota and SCFAs is lacking, and only female mice were evaluated, which limits the understanding of the effects of HYP on both sexes. ConclusionsHYP can improve CRS-induced depressive-like behaviors in mice, which is associated with regulating the gut microbiota and SCFAs concentration.

Epigenetic processes associated with neonatal spinal transection.

In early development, the spinal cord in healthy or disease states displays remarkable activity-dependent changes in plasticity, which may be in part due to the increased activity of brain derived neurotrophic factor (BDNF). Indeed, BDNF delivery has been efficacious in partially ameliorating many of the neurobiological and behavioral consequences of spinal cord injury (SCI), making elucidating the role of BDNF in the normative developing and injured spinal cord a critical research focus. Recent work in our laboratory provided evidence for aberrant global and locus-specific epigenetic changes in methylation of the Bdnf gene as a consequence of SCI. In the present study, animals underwent thoracic lesions on P1, with cervical and lumbar tissue being later collected on P7, P14, and P21. Levels of Bdnf expression and methylation (exon IX and exon IV), in addition to global methylation levels were quantified at each timepoint. Results indicated locus-specific reductions of Bdnf expression that was accompanied by a parallel increase in methylation caudal to the injury site, with animals displaying increased Bdnf expression at the P14 timepoint. Together, these findings suggest that epigenetic activity of the Bdnf gene may act as biomarker in the etiology and intervention effort efficacy following SCI.

Niuhuang Qingxin Wan ameliorates depressive-like behaviors and improves hippocampal neurogenesis through modulating TrkB/ERK/CREB signaling pathway in chronic restraint stress or corticosterone challenge mice.

Introduction: Chronic stress-associated hormonal imbalance impairs hippocampal neurogenesis, contributing to depressive and anxiety behaviors. Targeting neurogenesis is thus a promising antidepressant therapeutic strategy. Niuhuang Qingxin Wan (NHQXW) is an herbal formula for mental disorders in Traditional Chinese Medicine (TCM) practice, but its anti-depressant efficacies and mechanisms remain unverified. Methods: In the present study, we tested the hypothesis that NHQXW could ameliorate depressive-like behaviors and improve hippocampal neurogenesis by modulating the TrkB/ERK/CREB signaling pathway by utilizing two depression mouse models including a chronic restraint stress (CRS) mouse model and a chronic corticosterone (CORT) stress (CCS) induced mouse model. The depression-like mouse models were orally treated with NHQXW whereas fluoxetine was used as the positive control group. We evaluated the effects of NHQXW on depressive- and anxiety-like behaviors and determined the effects of NHQXW on inducing hippocampal neurogenesis. Results: NHQXW treatment significantly ameliorated depressive-like behaviors in those chronic stress mouse models. NHQXW significantly improved hippocampal neurogenesis in the CRS mice and CCS mice. The potential neurogenic mechanism of NHQXW was identified by regulating the expression levels of BDNF, TrkB, p-ERK (T202/T204), p-MEK1/2 (S217/221), and p-CREB (S133) in the hippocampus area of the CCS mice. NHQXW revealed its antidepressant and neurogenic effects that were similar to fluoxetine. Moreover, NHQXW treatment revealed long-term effects on preventing withdrawal-associated rebound symptoms in the CCS mice. Furthermore, in a bioactivity-guided quality control study, liquiritin was identified as one of the bioactive compounds of NHQXW with the bioactivities of neurogenesis-promoting effects. Discussion: Taken together, NHQXW could be a promising TCM formula to attenuate depressive- and anxiety-like behaviors against chronic stress and depression. The underlying anti-depressant mechanisms could be correlated with its neurogenic activities by stimulating the TrkB/ERK/CREB signaling pathway.