analysis-learning-memory-ability-an-alzheimer-s-disease-mouse-model

Analysis of Learning and Memory Ability in an Alzheimer's Disease Mouse Model using the Morris Water Maze

A Morris water maze (MWM) experiment forces experimental animals to swim and learn to find a platform hidden in the water. It is widely used in scientific ...

Beijing University of Chinese Medicine

Ischemic stroke is one of the main causes of death and disablement globally. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is established as a sensor of detecting cellular damage and modulating inflammatory responses to injury during the progress of ischemic stroke. Inhibiting or blocking the NLRP3 inflammasome at different stages, including expression, assembly, and secretion, may have great promise to improve the neurological deficits during ischemic stroke. The current review provides a comprehensive summary of the current understanding in the literature of the molecular structure, expression, and assembly of the NLRP3 inflammasome, and highlights its potential as a novel therapeutic target for ischemic stroke.

Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review).

Post-stroke depression (PSD) is one of the most frequent complications of stroke. The Yi-nao-jie-yu prescription (YNJYP) is an herbal prescription widely used as a therapeutic agent against PSD in traditional Chinese medicine. Disruption of adult neurogenesis has attracted attention as a potential cause of cognitive pathophysiology in neurological and psychiatric disorders. The Notch signaling pathway plays an important role in neurogenesis. This study investigated the effects of YNJYP on adult neurogenesis and explored its underlying molecular mechanism in a rat model of PSD that is established by middle cerebral artery occlusion and accompanied by chronic immobilization stress for 1 week. At 2, 4, and 8 weeks, depression-like behavior was evaluated by a forced swim test (FST) and sucrose consumption test (SCT). Neurogenesis was observed by double immunofluorescence staining. Notch signals were detected by real-time polymerase chain reaction. The results show that, at 4 weeks, the immobility time in the FST for rats in the PSD group increased and the sucrose preference in the SCT decreased compared with that in the stroke group. Therefore, YNJYP decreased the immobility time and increased the sucrose preference of the PSD rats. Further, PSD interfered with neurogenesis and decreased the differentiation toward neurons of newly born cells in the hippocampal dentate gyrus, and increased the differentiation toward astrocytes, effects that were reversed by YNJYP, particularly at 4 weeks. At 2 weeks, compared with the stroke group, expression of target gene  mRNA transcripts in the PSD group decreased, but increased after treatment with YNJYP. At 4 weeks, compared with the stroke group, the expression of Notch receptor  mRNA transcripts in the PSD group decreased, but also increased after treatment with YNJYP. Overall, this study indicated that disturbed nerve regeneration, including the increased numbers of astrocytes and decrease numbers of neurons, is a mechanism of PSD, and Notch signaling genes dynamically regulate neurogenesis. Moreover, YNJYP can relieve depressive behavior in PSD rats, and exerts a positive effect on neurogenesis by dynamically regulating the expression of Notch signaling genes.

Yi-nao-jie-yu Prescription Exerts a Positive Effect on Neurogenesis by Regulating Notch Signals in the Hippocampus of Post-stroke Depression Rats.

 Most previous studies have found that human intestinal microbiota affect the symptoms of autism spectrum disorder (ASD), especially gastrointestinal (GI) symptoms, but regarding this, there is limited data of non-western ethnicity. Probiotics can reconstitute the host intestinal microbiota and strengthen gastrointestinal function, however, clinical data proving the effect of probiotics treatment on ASD is lacking.  This study explored the significant differences between ASD and neurotypical (NT), and the improvement of applied behavior analysis (ABA) training in combination with probiotics, vs. ABA training only.  We found significant differences between the ASD group and the NT group in the evenness of the intestinal microbiota and the relative abundance of the bacterial phyla and genus. At the phylum level, relative abundance of  in the ASD group was significantly lower than in the NT group. At the genus level, the relative abundance of , and  in the ASD group was significantly lower than that in the NT group. After a 4-week ABA training program in combination with probiotics treatment, the  and GI scores decreased more than the control group with ABA training only.  Our findings suggest that intestinal microbiota is different between the NT children and the ASD children with or without GI problems. In combination with ABA training, probiotics treatment can bring more benefit to ASD children. Clinical trials with a more rigorous design and larger sample size are indispensable for further validation.

Characterization of Intestinal Microbiota and Probiotics Treatment in Children With Autism Spectrum Disorders in China.

Alzheimer's disease (AD) is a neurodegenerative disease, yet there is no effective treatment. Electroacupuncture (EA) is a complementary alternative medicine approach. In clinical and animal studies, EA promotes cognition in AD and vascular dementia. It has been previously reported that cognitive decline in AD might be closely related to reduced glucose intake in the brain. It is worth mentioning that the regions of glucose hypometabolism are usually found to be associated with neuroinflammation.

Electroacupuncture Enhances Cognition by Promoting Brain Glucose Metabolism and Inhibiting Inflammation in the APP/PS1 Mouse Model of Alzheimer's Disease: A Pilot Study.

Post-stroke depression (PSD) is the most common neuropsychiatric complication after a stroke, though its neuropathological characteristics have not been fully elucidated. Comprehensive and non-invasive magnetic resonance (MR) assessment techniques are urgently needed for current research, as diffusion tensor imaging (DTI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS) can allow for a comprehensive assessment of neuropathological changes in the brain. These techniques can provide information about microscopic tissue integrity, cerebral perfusion, and cerebral metabolism, and can serve as powerful tools for investigating neurophysiological changes associated with PSD. Yi-nao-jie-yu decoction (YNJYD) is a Chinese herbal formulation based on the theory of traditional Chinese medicine, with demonstrated clinical efficacy in the treatment of PSD. The aim of this study was to use these MR techniques to evaluate changes in PSD and YNJYD-treated rats. This is the first experimental study in animals to investigate neuropathological changes associated with PSD using a combination of multiple MR techniques, including DTI, ASL, and MRS. In addition, we investigated the effect of YNJYD in a rat model of PSD by assessing changes in brain tissue microstructure, brain metabolism, and cerebral perfusion. First, depressive-like behaviors of PSD rats were assessed by the open field test (OFT), sucrose preference test (SPT), and Morris water maze (MWM) test, and then the integrity of the rats' microstructure was assessed by DTI, the levels of regional cerebral perfusion were assessed by ASL, and changes in the relative concentrations of brain metabolites were determined by MRS. The results showed that OFT and SPT scores were significantly reduced in PSD rats, as was performance in the MWM; these PSD-associated changes were attenuated in rats administered YNJYD, with improved depressive-like behaviors evidenced by increased OFT and SPT scores and improved performance in the MWM task. Furthermore, we found that PSD rats had lower perfusion levels in the prefrontal cortex (PFC) and hippocampus (HP), microstructural damage, and abnormal changes in the concentrations of brain metabolites; YNJYD exerted therapeutic effects on PSD rats by improving microcirculation in the PFC and HP, regulating glutamatergic systems and membrane phospholipid metabolism, and repairing microstructural damage.

Multimodal Magnetic Resonance Imaging and Therapeutic Intervention With Yi-nao-jie-yu Decoction in a Rat Model of Post-stroke Depression.

Spinal cord injury (SCI) is one of the serious central nervous system injuries and the incidence of SCI continues to increase. Previous studies have indicated that electroacupuncture (EA) is beneficial for promoting recovery after SCI. In the present study, we attempted to evaluate how EA can promote the neural repair in SCI model rats by observing changes in the Notch signaling pathway. Experimental rats were randomly divided into four groups. Each group had its own intervention period: 1 day, 7 days, 14 days, and 28 days, and five randomized subgroups: blank control (B) group, blank electroacupuncture (BE) group, sham operation (S) group, model control (M) group and EA group. Animals in the EA group and the BE group were treated with EA at Dazhui (GV14) and Mingmen (GV4) acupoints for 20 min. After the intervention period, the Basso-Beattie-Bresnahan (BBB) score was used to evaluate the neurological function. We found that BBB score increased in EA-treated groups. Hematoxylin and eosin staining was used to observe pathological changes in the injured spinal cord and the results showed that EA therapy could promote the repair of injured spinal cord tissue. Immunohistochemistry and Western blot methods were used to detect the expression of proteins Delta1, Presenilin1, Hes1, and Hes5 in the injured spinal cord. The results showed that the expression levels of Delta1, Presenilin1, Hes1, and Hes5 increased significantly after SCI and decreased after EA treatment. Our study suggested that the possible mechanism by which EA could benefit the recovery after SCI in rats may include inhibiting the Notch signaling pathway and regulating the downstream proteins expression. In addition, our study can provide reference for selecting acupoints and treatment cycle in the treatment of SCI.

Electroacupuncture in promoting neural repair after spinal cord injury: Inhibiting the Notch signaling pathway and regulating downstream proteins expression.

 This study aimed to observe the effects of lipopolysaccharide (LPS) intraperitoneal (i.p.) injection on rats and investigate how neuroinflammation contributes to the pathogenesis of depression in Parkinson's disease (dPD).  Rats were administered LPS (0.5 mg/kg, i.p.) for either 1, 2, or 4 consecutive days to establish a rat model of dPD. The sucrose preference test (SPT), the open field test (OFT), and the rotarod test evaluated depression-like and motor behaviors. Magnetic resonance imaging was used to detect alterations in the intrinsic activity and the integrity of white matter fibers in the brain. The expression of c-Fos, ionized calcium-binding adapter molecule (Iba-1), and tyrosine hydroxylase (TH) was evaluated using immunohistochemistry. The concentration of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) was measured using Luminex technology.  LPS i.p. injections decreased sucrose preference in the SPT, horizontal and center distance in the OFT, and standing time in the rotarod test. The intrinsic activities in the hippocampus (HIP) were significantly reduced in the LPS-4 d group. The integrity of white matter fibers was greatly destroyed within 4 days of LPS treatment. The expression of c-Fos and Iba-1 in the prefrontal cortex, HIP, and substantia nigra increased dramatically, and the number of TH neurons in the substantia nigra decreased considerably after LPS injection. The levels of IL-6, TNF-α, and IL-10 were higher in the LPS-4 d group than those in the control group.  Injection of LPS (0.5 mg/kg, i.p.) for 4 consecutive days can activate microglia, cause the release of inflammatory cytokines, reduce intrinsic activities in the HIP, destroy the integrity of white matter fibers, induce anhedonia and behavioral despair, and finally lead to dPD. This study proved that LPS injection (0.5 mg/kg, i.p.) for 4 consecutive days could be used to successfully create a rat model of dPD.

LPS activates neuroinflammatory pathways to induce depression in Parkinson's disease-like condition.

To determine the neuroprotective effects of fluoxetine on depression-like and motor behaviors in rats treated with lipopolysaccharide (LPS) and the mechanisms involved.

Article	Year
Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review). International journal of molecular medicine\| PubMed ID: 30280193	2018
Yi-nao-jie-yu Prescription Exerts a Positive Effect on Neurogenesis by Regulating Notch Signals in the Hippocampus of Post-stroke Depression Rats. Frontiers in psychiatry\| PubMed ID: 30386260	2018
Characterization of Intestinal Microbiota and Probiotics Treatment in Children With Autism Spectrum Disorders in China. Frontiers in neurology\| PubMed ID: 31749754	2019
Electroacupuncture Enhances Cognition by Promoting Brain Glucose Metabolism and Inhibiting Inflammation in the APP/PS1 Mouse Model of Alzheimer's Disease: A Pilot Study. Journal of Alzheimer's disease : JAD\| PubMed ID: 32741819	2020
Multimodal Magnetic Resonance Imaging and Therapeutic Intervention With Yi-nao-jie-yu Decoction in a Rat Model of Post-stroke Depression. Frontiers in psychiatry\| PubMed ID: 33329096	2020
Electroacupuncture in promoting neural repair after spinal cord injury: Inhibiting the Notch signaling pathway and regulating downstream proteins expression. Anatomical record (Hoboken, N.J. : 2007)\| PubMed ID: 34636492	2021
LPS activates neuroinflammatory pathways to induce depression in Parkinson's disease-like condition. Frontiers in pharmacology\| PubMed ID: 36278237	2022
Fluoxetine shows neuroprotective effects against LPS-induced neuroinflammation via the Notch signaling pathway. International immunopharmacology\| PubMed ID: 36461606	2022

Huiling Tian

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