DG Regions Research Articles

Protective effects of polydatin amphiphilic chitosan nanocarriers against an aluminum chloride-induced model of Alzheimer's disease in rats: relevance to its anti-inflammatory and antioxidant effects.

Alzheimer's disease (AD) is the most frequent cause of dementia. Since there are complex pathophysiological mechanisms behind AD, and there is no effective treatment strategy, it is necessary to introduce novel multi-targeting agents with fewer side effects and higher efficacy. Polydatin (PD) is a naturally occurring resveratrol glucoside employing multiple mechanisms toward neuroprotection. In the current study, the anti-AD mechanisms of a novel amphiphilic chitosan nanocarrier formulation (ACN) of PD (NPD) were studied. After preparing the amphiphilic chitosan nanoformulation (i.e., NPD), physicochemical properties were assessed, including particle size, zeta potential, drug loading, drug release, MTT, Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). For in vivo analysis, aluminum chloride (AlCl3) was injected intraperitoneally for 14 days to induce AD in male Albino Wistar rats. To examine the anti-AD mechanisms of NPD, a total of 36 rats were divided into six groups of six. Behavioral tests, including open field, Y-maze, elevated plus maze, and shuttle box were done on days 7, 8, 14, and 15. Additionally, zymography, biochemical analysis, and histological studies were done. NPD, as a newly synthesized formulation for PD, potentially improved memory and cognitive behavioral parameters and reduced the activity ofinflammatory matrix metalloproteinase 9 (MMP9) and serum nitrite levels, while increasing anti-inflammatory MMP2, antioxidant catalase, and glutathione. NPD also prevented morphological changes and increased neuronal survival in the CA2, CA4, and DG regions of the rat hippocampus. In conclusion,NPD is a novel formulation against AD through anti-inflammatory, antioxidant, and neuroprotective mechanisms.

Effect of proanthocyanidins on cognitive improvement in thyroxin-induced aging mice.

As the population ages, functional dietary supplements are increasingly used to reduce age-related diseases, especially in the field of cognitive impairment. In this study, a thyroxine (Th)-induced aging model was established, and the effect of proanthocyanidins (Pc) on cognitive impairment of aging mice was evaluated based on cognitive ability, neuroinflammation and immune level. The results showed that Pc significantly reduced AchE activity compared to the Model group, improving learning deficits and spatial memory in aged mice (P < 0.01). Further study showed that Pc could maintain the organism's redox balance, markedly increasing T-AOC, GSH, and SOD levels (P < 0.01) while reducing MPO and MDA levels (P < 0.01). Pc also improved systemic inflammation, raising the levels of the anti-inflammatory cytokine PF4 and significantly lowering pro-inflammatory factors in the blood (P < 0.01). In the DG region of the hippocampus, Pc effectively repaired nerve damage, inhibited the over-activation of microglia and astrocytes, down-regulated GFAP and IBA-1 proteins (P < 0.01), and then reduced neuroinflammation. Additionally, Pc supplementation also significantly increased the levels of WBC, Lymph, Mid, and Gran in aged mice (P < 0.01), aiding in the recovery of leukocyte counts. At the same time, the CD3+ level and CD4+/CD8+ ratio were significantly increased (P < 0.01) to maintain the dynamic balance of lymphocyte subsets in aging mice and enhance the immune capacity of aging mice. The study revealed that Pc, as a dietary supplement, can effectively alleviate cognitive impairment in the elderly population. This provides a new dietary nutrition supplement strategy for the health of the aging population.

Gender Differences in Dendritic Damage, Gut Microbiota Dysbiosis, and Cognitive Impairment During Aging Processes.

Cognitive impairment is a common and feared characteristic of aging processes, and one key mechanism of cognition is hippocampal synaptic structure. Previous studies have reported that gut microbiota dysbiosis occurred in neurodegenerative diseases and other brain disorders with cognitive impairment. However, it is not clear how gender differences affect cognitive impairment in aging processes and whether they affect synaptic structure and gut microbiota. Here, we studied the gender differences in cognitive ability, dendritic morphology, and gut microbiota of adult, middle-, and old-aged rats. The cognitive ability of rats using was assessed by the Y-maze SAB test, the light/dark discrimination test, and the MWM test. Dendritic morphology was investegated by Golgi staining. Microbiota composition, diversity and richness were analyzed by 16S rRNA gene sequencing. The results showed that the cognitive ability of old-aged rats was decreased than adult and middle-aged rats in the spontaneous alternation behavior test, the light/dark discrimination test in Y-maze, and the MWM test; males have better cognitive ability than the females for middle-aged rats. The neuronal dendritic structures of CA1, CA3, and DG regions of the hippocampus were damaged to different degrees during aging, and the spine loss of females was more than that of males in CA1 and CA3 of middle-aged rats. In addition, the microbial diversity of gut microbiota was significantly decreased in old-aged male rats; the distribution and composition of microbiota communities were different between male and female rats at different ages. These findings revealed that cognitive impairment in aged rats might result from dendritic damage in the hippocampus and gut microbiota dysbiosis, which provides direct evidence that gender differences in dendritic damage and gut microbiota dysbiosis might associate with cognitive impairment in naturally aged rats.

Upstream regulation of microRNA-9 through a complex cellular machinery during neurogenesis

SummaryWhile microRNAs (miRs) like miR-9 are crucial for neurogenesis and neuronal differentiation, their regulatory mechanisms are not well understood. miR-9 is highly expressed in the brain and plays a significant role in neurogenesis. Using the Collaborative Cross resource, we identified significant quantitative trait loci (QTL) through genetic analyses. We then characterized over 130 candidate genes within these QTL regions using RNA interference, qPCR, and neuronal differentiation assays, narrowing them down to 13 promising candidates. Among these, Panx2, Polr1c, and Mgea5 were found to colocalize in the neurogenic niches of the SVZ and DG regions, as shown by immunofluorescence. Further ChIP-seq and Co-IP analyses revealed their interaction and binding to the miR-9 locus, forming a DNA-protein regulatory complex we termed ’miRSome-9.’ A 3C/ChIP-loop assay confirmed the chromatin organization of miRSome-9 at the miR-9 locus, shedding light on the upstream mechanisms regulating miR-9 expression during neurogenesis.

The Kv7 channel opener Retigabine reduces neuropathology and alleviates behavioral deficits in APP/PS1 transgenic mice

Hyperexcitability of neuronal networks is central to the pathogenesis of Alzheimer's disease (AD). Pharmacological activation of Kv7 channels is an effective way to reduce neuronal firing. Our results showed that that pharmacologically activating the Kv7 channel with Retigabine (RTG) can alleviate cognitive impairment in mice without affecting spontaneous activity. RTG could also ameliorate damage to the Nissl bodies in cortex and hippocampal CA and DG regions in 9-month-old APP/PS1 mice. Additionally, RTG could reduce the Aβ plaque number in the hippocampus and cortex of both 6-month-old and 9-month-old mice. By recordings of electroencephalogram, we showed that a decrease in the number of abnormal discharges in the brains of the AD model mice when the Kv7 channel was opened. Moreover, Western blot analysis revealed a reduction in the expression of the p-Tau protein in both the hippocampus and cortex upon Kv7 channel opening. These findings suggest that Kv7 channel opener RTG may ameliorate cognitive impairment in AD, most likely by reducing brain excitability.

A method for making and extracting amplitude of low frequency fluctuation (ALFF) in specific regions of interest (ROI) of macaque

Objective: This study aimed to develop a method for delineating regions of interest and extracting amplitude of low-frequency fluctuation (ALFF) values from specific brain regions using the macaque brain atlas to enhance analysis specificity and accuracy. Methods: The INIA19 template was utilized to create a hippocampal mask, following which the ALFF in the hippocampus was derived from resting-state functional magnetic resonance imaging (fMRI) data obtained from three macaques. Results:Bilateral hippocampal and region-specific masks were successfully generated. Analysis of low-frequency amplitude values revealed significant differences in activity levels between the left and right hippocampi, CA1, CA2 regions. Specifically, the left hippocampus, CA1, and CA2 regions exhibited higher amplitude activity compared to their right-sided counterparts. Conversely, no significant differences were observed between the left CA3 and right DG regions and their contralateral counterparts. Conclusions: Implementing the production and extraction of ALFF values in specific brain regions facilitates a deeper understanding of brain activity complexities and offers novel insights into brain functional networks in cognitive neuroscience.

Neuroprotective Effect of Chlorogenic Acid in an Animal Model of Sporadic Alzheimer's Disease Induced by Streptozotocin.

Alzheimer's Disease is a degenerative neurological condition which leads to a decline in memory and cognitive function. Chlorogenic Acid (CGA) presents properties including neuroprotective, antioxidant and anti-inflammatory. The aim of this study was to examine the impact of CGA on cognitive impairments, neuroinflammation and neuronal damage in mice submitted to an experimental model of Sporadic Alzheimer Disease (SAD) induced by intracerebroventricular administration of streptozotocin (ICV-STZ). Male Swiss mice received bilateral ICV-STZ injections (3mg/Kg) on days 1 and 3. The treatment with CGA (5mg/Kg, orally) or vehicle (water, orally), was initiated and continued for 26days, starting 2h after the second induction procedure. At first, there was no change in serum glucose levels after SAD induction. ICV-STZ induces impairments in aversive, recognition, and spatial memory, while CGA treatment significantly alleviated these memory deficits. Furthermore, locomotor activity, working memory, and anxiety-related activities remained unaffected by the treatments. CGA treatment protects against ICV-STZ-induced increase in the nitrite/nitrate and TBARS levels. ICV-STZ induced a reduction in viable cells, depletion of BDNF, and triggered astrogliosis and microgliosis in the cortex and hippocampus. Treatment with CGA preserves viable cell count in the prefrontal cortex, CA1, and CA3 regions of the hippocampus. Additionally, it prevented BDNF depletion in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions), and mitigated astrogliosis and microgliosis in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions). These findings indicate the neuroprotective effects of CGA, underscoring their potential as therapeutic agents or adjuncts in the treatment of SAD.

Design of a 1 × 4 micro-magnetic stimulation device and its targeted, coordinated regulation on LTP of Schaffer-CA1 in the hippocampus of rats

Magnetic technology has been a hotspot of neuromodulation research in recent years. However, magnetic coil is limited by their size, and it is impossible to realize precise targeted magnetic stimulation to the target area at the cellular scale. To this end, this study designs a 1 × 4 array micro-magnetic stimulation (μMS) device with four sub-millimeter-sized elements, enabling precise magnetic stimulation of the CA1-CA3-DG tri-synaptic positions in the rat hippocampal region. First, it is determined that 70 KHz/2 mT/1 min magnetic stimulation parameter has a modulatory effect on the long-term potentiation (LTP) of Schaffer-CA1 in rat hippocampus. Then, a 1 × 4 array μMS device is used to perform magnetic stimulation at 70 KHz/2 mT/1 min, targeting the CA1, CA3, and DG regions individually with single-point magnetic stimulation; and multi-region magnetic stimulation is applied to the double-point targeting regions of CA1-CA3, CA1-DG, and CA3-DG, as well as the triple-point targeting region of CA1-CA3-DG, so as to investigate the regulation of LTP by single-region magnetic stimulation and multi-region magnetic stimulation. The experimental results indicate that, in the case of single-region magnetic stimulation, the magnitude of the increase in LTP in the CA1 region is the greatest, followed by the CA3 region, while the effect of magnetic stimulation on the DG region is less pronounced. In multi-region magnetic stimulation, synergistic magnetic stimulation of the three-point CA1-CA3-DG results in a greater increase in LTP compared to stimulation of two individual areas, and the enhancement of LTP induction with multi-region magnetic stimulation surpasses that of single-region stimulation. This study has implications for the collaborative targeted magnetic stimulation application of arrayed micro-magnetic devices.

AdipoRon Ameliorates Synaptic Dysfunction and Inhibits tau Hyperphosphorylation through the AdipoR/AMPK/mTOR Pathway in T2DM Mice.

There is growing evidence showing that adiponectin (APN) can improve Alzheimer's disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

Exploring the Therapeutic Potential of Baicalin: Mitigating Anxiety and Depression in Epileptic Rats.

Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting. The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model. Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1β (IL-1β) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding. Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1β signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1β. This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA.

The effect of magnesium sulfate on memory and anxiety-like behavior in a rat model: an investigation of its neuronal molecular mechanisms

ABSTRACT Background Anxiety is an adaptive response to potentially threatening conditions. Excessive and uncontrolled anxiety responses become nonadaptive and cause anxiety disorders. To better understand the anxiety-modulating effects of Mg sulfate, behavioral test batteries in the assessment of anxiety and learning and memory functions were performed simultaneously over a time period. This study also examines the effects of Mg sulfate compared to diazepam, an anxiolytic drug with amnestic effects on anxiety-like behavior, as well as possible oxidative-nitrosative stress and hippocampal changes in male rats exposed to predator odor. Methods Young adult Sprague-Dawley male rats were used. The rats were assessed using a comprehensive neurobehavioral test battery consisting of novel object recognition, open field, and successive alleys tasks. Anxiety was induced by cat odor, and diazepam and Mg were used as study drugs. Of the frontal cortex and hippocampus, the state of total oxidant and antioxidant and NO levels and histological examination of hippocampal CA1, CA2, CA3, and DG regions were performed. Results Diazepam- and Mg-treated rats showed an improvement in anxiety-related behavior to predator odors. Furthermore, Mg treatment alleviated some of the increasing oxidative stress in the frontal cortex and hippocampus of rats, while diazepam treatment in particular enhanced hippocampal oxidant and antioxidant activity. In addition, brain NO increase induced by animal odor exposure or diazepam treatment was ameliorated by Mg administration. Conclusions Overall, our work suggests that Mg had a partial anxiolytic effect on anxiety-like behaviors, although not as much as diazepam, and this effect varied depending on the dose. Mg treatment might counteract increased oxidative stress and elevated NO levels in the brain.

Long-Term Alterations in Motor Skills, Neurogenesis and Astrocyte Numbers following Transient Cerebral Ischemia in Mice.

Background and Objectives. Neurogenesis is an integral process in post-stroke recovery, involving the recruitment of proliferating neuroblasts from neurogenic niches of the mammal brain. However, the role of neurogenesis in the long-term restoration following ischemic stroke is fragmented. Post-stroke motor dysfunction includes challenges in the proper, coordinated use of hands and is present in roughly two-thirds of human patients. In this study, we investigated chronic behavioral and biochemical alterations after transient cerebral ischemia in adult male mice. Materials and Methods: Twelve-week-old C57BL/6N male mice were used, and fMCAo lasting 60 min was induced. At multiple timepoints after fMCAo induction, a single pellet reaching task was performed. Six months after the procedure, we immunohistochemically determined the number of proliferating neuroblasts (BrdU and DCX-positive) and the number of differentiated astrocytes (GFAP-positive) in both brain hemispheres. Results: The reaching ability of fMCAo mice was impaired from one month to six months after the induction of ischemia. Neuroblast proliferation was increased in the ipsilateral SVZ, whereas GFAP+ cell count was elevated in the hippocampal DG of both hemispheres of the fMCAo group mice. Conclusions: Our current report demonstrates the long-term effects of transient cerebral ischemia on mice functional parameters and neurogenesis progression. Our data demonstrate that transient cerebral ischemia promotes a long-lasting regenerative response in the ipsilateral brain hemisphere, specifically in the neurogenic SVZ and DG regions.

Running exercise improves astrocyte loss, morphological complexity and astrocyte-contacted synapses in the hippocampus of CUS-induced depression model mice

Although the antidepressant effects of running exercise have been widely reported, further research is still needed to determine the structural bases for these effects. Astrocyte processes physically contact many synapses and directly regulate the numbers of synapses, but it remains unclear whether running exercise can modulate astrocyte morphological complexity and astrocyte-contacted synapses in the hippocampus of the mice with depressive-like behavior. Male C57BL/6 J mice underwent four weeks of running exercise after four weeks of chronic unpredictable stress (CUS). The sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess anhedonia in mice. Western blotting was used to measure the expression of astrocyte- and synapse-related proteins. Immunofluorescence and 3D reconstruction were used to quantify the density and morphology of astrocytes, and astrocyte-contacted synapses in each hippocampal subregion. Four weeks of running exercise alleviated depressive-like symptoms in mice. The expression of astrocyte- and synapse-related proteins in the hippocampus; astrocyte process lengths, process numbers, and dendritic arborization; and the number of astrocyte-contacted PSD95 positive synapses in the CA2–3 and DG regions were significantly decreased in the mice with depressive-like behavior, and running exercise successfully reserved these changes. Running exercise improved the decreases in astrocyte morphological complexity and astrocyte-contacted PSD95 positive synapses in the CA2–3 and DG regions of the mice with depressive-like behavior, suggesting that the physical interactions between astrocytes and synapses can be increased by running exercise, which might be an important structural basis for the antidepressant effects of running exercise.

Spatially resolved transcriptome of the aging mouse brain.

Brain aging is associated with cognitive decline, memory loss and many neurodegenerative disorders. The mammalian brain has distinct structural regions that perform specific functions. However, our understanding in gene expression and cell types within the context of the spatial organization of the mammalian aging brain is limited. Here we generated spatial transcriptomic maps of young and old mouse brains. We identified 27 distinguished brain spatial domains, including layer-specific subregions that are difficult to dissect individually. We comprehensively characterized spatial-specific changes in gene expression in the aging brain, particularly for isocortex, the hippocampal formation, brainstem and fiber tracts, and validated some gene expression differences by qPCR and immunohistochemistry. We identified aging-related genes and pathways that vary in a coordinated manner across spatial regions and parsed the spatial features of aging-related signals, providing important clues to understand genes with specific functions in different brain regions during aging. Combined with single-cell transcriptomics data, we characterized the spatial distribution of brain cell types. The proportion of immature neurons decreased in the DG region with aging, indicating that the formation of new neurons is blocked. Finally, we detected changes in information interactions between regions and found specific pathways were deregulated with aging, including classic signaling WNT and layer-specific signaling COLLAGEN. In summary, we established a spatial molecular atlas of the aging mouse brain (http://sysbio.gzzoc.com/Mouse-Brain-Aging/), which provides important resources and novel insights into the molecular mechanism of brain aging.

L-methionine and the L-type Ca2+ channel agonist BAY K 8644 collaboratively contribute to the reduction of depressive-like behavior in mice.

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.

Rosmarinic acid alleviate CORT-induced depressive-like behavior by promoting neurogenesis and regulating BDNF/TrkB/PI3K signaling axis

Rosmarinic acid (RA), a natural phenolic acid compound with a variety of bioactive properties. However, the antidepressant activity and mechanism of RA remain unclear. The aim of this study is to investigate the effects and potential mechanisms of RA on chronic CORT injection induced depression-like behavior in mice. Male C57BL/6 J mice were intraperitoneally injected with CORT (10 mg/kg) and were orally given RA daily (10 or 20 mg/kg) for 21 consecutive days. In vitro, the HT22 cells were exposed to CORT (200 μM) with RA (12.5, 25 or 50 μM) and LY294002 (a PI3K inhibitor) or ANA-12 (a TrkB inhibitor) treatment. The depression-like behavior and various neurobiological changes in the mice and cell injury and levels of target proteins in vitro were subsequently assessed. Here, RA treatment decreased the expression of p-GR/GR, HSP90, FKBP51, SGK-1 in mice hippocampi. Besides, RA increased the average optical density of Nissl bodies and number of dendritic spines in CA3 region, and enhanced Brdu and DCX expression and synaptic transduction in DG region, as well as up-regulated both the BDNF/TrkB/CREB and PI3K/Akt/mTOR signaling. Moreover, RA reduced structural damage and apoptosis in HT22 cells, increased the differentiation and maturation of them. More importantly, LY294002, but not ANA-12, reversed the effect of RA on GR nuclear translocation. Taken together, RA exerted antidepressant activities by modulating the hippocampal glucocorticoid signaling and hippocampal neurogenesis, which related to the BDNF/TrkB/PI3K signaling axis regulating GR nuclear translocation, provide evidence for the application of RA as a candidate for depression.

Drug-detecting bioelectronic nose based on odor cue memory combined with a brain computer interface

The international drug situation is increasingly, various new drugs are hidden in public places through changing forms and packaging, which brings new challenges to drug enforcement. This study proposes a drug-detecting bioelectronic nose based on odor cue memory combined with brain-computer interface and optogenetic regulation technologies. First, the rats were trained to generate positive memories of drug odors through food reward training, and multichannel microelectrodes were implanted into the DG region of the hippocampus for responsible memory retrieval, the spike signals of individual neurons and the local field potential signals of population neurons in the brain region were collected for pattern recognition and analysis. Preliminary experimental results have shown that when low-dose drugs are buried in a hidden area, rats can find the location of the drugs in a very short time, and when close to the relevant area, there is a significant change in the energy value and time-frequency spectrum signal coupling of the returned data, which can be extracted to indicate that the rats have found the drugs. Second, we labled the neuronal activity marker c-fos and revealed more robust activation in the DG region following odor detection. We modulated these neurons through neuroregulatory technology, so that the rats could recognize drugs by retrieving memories more quickly. We conceive that the drug-detecting rat robot can detect trace amounts of various drugs in complex terrain and multiple scenes, which is of great significance for anti-drug work in the future.

Effect of Formononetin on Lipopolysaccharide-Induced Depressive-Like Behaviors and Neuroinflammation in Mice

Abstract Objective The objective of this article is to explore the effect of formononetin (FMN) on depressive-like behaviors and neuroinflammation in lipopolysaccharide (LPS)-induced mice.Methods After acclimatization, male Institute of Cancer Research mice were randomly divided into normal group, LPS group, paroxetine group (20 mg/kg), FMN low-dose group (20 mg/kg, FMN20), and FMN high-dose group (40 mg/kg, FMN40), with eight mice in each group. The depressive-like behaviors were observed by sucrose preference test, tail suspension test (TST), and open field test. The protein and mRNA levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the hippocampus were determined by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. The expression level of ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampus was observed by immunofluorescence staining to evaluate the activation level of microglia. Results Compared with the control group, the sucrose preference rate, the activity time of the central area, the distance of the central area, and the number of times of entering the central area were significantly decreased in the LPS group (p &lt; 0.01), and the immobility time of TST was significantly prolonged (p &lt; 0.05), the expression levels of IL-6, IL-1β, and TNF-α protein and mRNA in hippocampus were significantly increased (p &lt; 0.01), and the fluorescence intensity of Iba-1 in CA1, CA3, and DG regions of hippocampus was significantly increased (p &lt; 0.01). Compared with the LPS group, the sucrose preference rate, central area activity time, central area activity distance, and the number of times of entering the central area were significantly increased (p &lt; 0.05 or p &lt;0.01) in the FMN group, and TST immobility time was significantly shortened (p &lt; 0.01), the expression levels of IL-6, IL-1β, and TNF-α protein and mRNA in the hippocampus were significantly decreased (p &lt; 0.05 or p &lt; 0.01), and the fluorescence intensity of Iba-1 in CA1, CA3, and DG regions of hippocampus was significantly decreased (p &lt; 0.01). Conclusion FMN could inhibit LPS-induced activation of microglia, reduce hippocampal neuroinflammation, and improve depressive-like behaviors in mice.

Neuroprotective Effects of Dammarane Sapogenins Against lipopolysaccharide-induced Cognitive Impairment, Neuroinflammation and Synaptic Dysfunction.

Neuroinflammation is a critical driver in the pathogenesis and progression of neurodegenerative disorders. Dammarane sapogenins (DS), a deglycosylated product of ginsenoside, possess a variety of potent biological activities. The present study aimed to explore the neuroprotective effects of DS in a rat model of neuroinflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS). Our study revealed that DS pretreatment effectively improved LPS-induced associative learning and memory impairments in the active avoidance response test and spatial learning and memory in Morris water maze test. DS also remarkably inhibited LPS-induced neuroinflammation by suppressing microglia overactivation, pro-inflammatory cytok ine release (TNF-α and IL-1β) and reducing neuronal loss in the CA1 and DG regions of the hippocampus. Importantly, pretreatment with DS reversed LPS-induced upregulation of HMGB1 and TLR4 and inhibited their downstream NF-κB signaling activation, as evidenced by increased IκBα and decreased p-NF-κB p65 levels. Furthermore, DS ameliorated LPS-induced synaptic dysfunction by decreasing MMP-9 and increasing NMDAR1 expression in the hippocampus. Taken together, this study suggests that DS could be a promising treatment for preventing cognitive impairments caused by neuroinflammation.

Study on mechanisms of acupuncture underlying improvement of CUMS-induced depression in rats based on tandem mass spectrometry proteomics technique

To investigate the possible mechanism of "regulating qi and relieving depression" acupuncture underlying improvement of chronic unpredictable mild stress (CUMS)-induced depression in rats by using Tandem Mass Tags(TMT) quantitative proteomics technique. Thirty-six male SD rats were randomly divided into control, model and acupuncture groups, with 12 rats in each group. The depression model was induced by CUMS stress for 21 days. After the depression model was successfully established, the rats in the acupuncture group received manual acupuncture stimulation at "Baihui" (GV20) and "Yintang" (GV24+) for 20 min, once daily for 21 days. Open field test, sugar water preference test and forced swimming test (FST) were used to evaluate the behavioral changes. TMT quantitative proteomics was used to obtain differential proteins in the hippocampus tissue and related signaling pathways enrichment was analyzed, followed by verifying differential protein pathways by using Western blot and immunofluorescence methods. Behavior tests showed that on the 21st and 42nd days, the horizontal crossing times, walking distance and percentage of sugar water consumption were significantly decreased (P<0.05), while the immobility time of FST was obviously increased (P<0.05) in the model group relevant to the control group. After acupuncture intervention, the horizontal crossing times, walking distance and percentage of sugar water consumption were significantly increased (P<0.05), and the immobility time was apparently decreased (P<0.05) in the acupuncture group relevant to the model group. The TMT quantitative proteomics of hippocampus tissue displayed that of the 71 differential proteins (model group vs control group), 32 was down-regulated and 39 up-regulated in the model group; and among the above 71 differential proteins, there were 20 differential proteins between acupuncture group and model group, 15 down-regulated and 5 up-regulated in the acupuncture group (vs the model group). The expression of Mapk8ipl was up-regulated in the model group (vs the control group) and down-regulated in the acupuncture group (vs the model group). GO and KEGG enrichment analysis showed that these acupuncture-related differential proteins mainly involve the regulation of blood coagulation system, MAPK signaling pathway, etc. We selected the MAPK/JNK signaling pathway related to depression for verification. Western blot showed that the expression levels of c-JUN and phosphorylated c-JUN terminal kinase (p-JNK) proteins in the hippocampus were up-regulated in the model group relevant to the control group (P<0.05); while the expression levels of c-JUN and p-JNK proteins in the hippocampus were down-regulated in the acupuncture group relevant to the model group (P<0.05). The results of immunofluorescence showed that the mean fluorescence intensity of c-JUN and p-JNK in hippocampal CA1, CA3 and DG regions was increased in the model group relevant to the control group (P<0.05), while the mean fluorescence intensity of c-JUN and p-JNK in hippocampal CA1, CA3 and DG regions was obviously lower in the acupuncture group than in the model group (P<0.05). Acupuncture for "regulating qi and relieving depression" can significantly improve depression-like behavior in CUMS-induced depression model rats, which involves multiple targets and multiple pathways, including MAPK/JNK signaling.