Rat Model Of Disease Research Articles

The protective effect of biotin supplementation and swimming training on cognitive impairment and mental symptoms in a rat model of Alzheimer's disease: A behavioral, biochemical, and histological study

Vitamin B (Vit B) plays a regulatory role in cognitive memory and learning. We examined the biochemical and behavioral effects of biotin supplementation (BS) and swimming training (ST) on Alzheimer's disease (AD), the most common type of dementia, in male rats. Sixty rats were randomly assigned to six groups: control, sham (receiving phosphate-buffered saline), AD (receiving a single injection of Aβ into the lateral ventricle), ST (for 28 days and before Aβ injection), and BS (receiving BS through oral gavage for 28 days before Aβ injection). The treatments were continued until the end of the behavioral tests. Learning and memory functions were investigated through the Morris water maze (MWM) and depression and anxiety-like behaviors were tested by elevated plus-maze (EPM) and forced swimming tests. In addition, oxidative stress biomarkers, such as total thiol groups (TTG) and malondialdehyde (MDA) in serum were assessed and histological studies were performed using brain tissues. In the AD group, Aβ increased the distance traveled and escape latency in the MWM, but co-administration of BS and ST attenuated the results of the MWM, EPM, and FST tests. Furthermore, BS decreased the litigious biochemical effects of Aβ by enhancing the levels of TTG, in addition to reducing serum MDA levels. The use of BS as a potent antioxidant improved Aβ-induced memory impairment. It attenuated oxidative stress biomarkers in the brain (number of Aβ plaques) and serum of AD rats. We provide evidence for the use of BS in neurodegenerative disorders, such as AD, to elucidate the possible mechanisms.

Modulation of oxidative stress and apoptosis by alteration of bioactive lipids in the pancreas, and effect of zinc chelation in a rat model of Alzheimer's disease

IntroductionIncreasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer's disease (AD). It is known that peripheral insulin resistance in the early stages of AD precedes and is a precursor to amyloid-β (Aβ) deposition. Although it is known that improving the CNS insulin sensitivity of AD patients is an important therapeutic goal and that the majority of insulin in the brain comes from the periphery, there has been little attention to the changes that occur in the pancreatic tissue of AD patients. Therefore, it is crucial to elucidate the mechanisms affecting insulin resistance in pancreatic tissue in AD. It is known that zinc (Zn2+) chelation is effective in reducing peripheral insulin resistance, cell apoptosis, cell death, and oxidative stress. ObjectiveIt was aimed to determine the changes in bioactive lipids, amylin (AIPP), oxidative stress and apoptosis in pancreatic cells in the early stages of Alzheimer's disease. The main aim is to reveal the therapeutic effect of the Cyclo-Z agent on these changes seen in the pancreas due to AD disease. MethodsAD and ADC rats were intracerebroventricular (i.c.v.) Aβ1–42 oligomers. Cyclo-Z gavage was applied to ADC and SHC rats for 21 days. First of all, the effects of AIPP, bioactive ceramides, apoptosis and oxidative stress on the pancreatic tissue of AD group rats were evaluated. Then, the effect of Cyclo-Z treatment on these was examined. ELISA kit was used in biochemical analyses. ResultsAIPP and ceramide (CER) levels and CER/ sphingosine-1 phosphate (S1P) ratio were increased in the pancreatic tissue of AD rats. It also increased the level of CER kinase (CERK), which is known to increase the concentration of CER 1-phosphate (C1P), which is known to be toxic to cells in the presence of excessive CER concentration. Due to the increase in CER level, it was observed that apoptosis and oxidative stress increased in the pancreatic cells of AD group rats. ConclusionCyclo-Z, which has Zn2+ chelating properties, reduced AD model rats' AIPP level and oxidative stress and could prevent pancreatic apoptosis. Similar therapeutic effects were not observed in the pancreatic tissue of Cyclo-Z administered to the SH group. For this reason, it is thought that Cyclo-Z agent may have a therapeutic effect on the peripheral hyperinsulinemia observed in the early stages of AD disease and the resulting low amount of insulin transported to the brain, by protecting pancreatic cells from apoptosis and oxidative stress by regulating their bioactive metabolites.

Reduction in Serum Concentrations of Uremic Toxins Driven by Bifidobacterium Longum Subsp. Longum BL21 is Associated with Gut Microbiota Changes in a Rat Model of Chronic Kidney Disease.

Gut microbiota dysbiosis and consequent impairment of gut barrier function, culminating in elevated levels of uremic toxins, are prevalent in chronic kidney disease (CKD) patients. These toxins, notably indoxyl sulphate (IS), indole-3-acetic acid (IAA), and trimethylamine oxide (TMAO), are implicated in a spectrum of CKD-related complications, including cardiovascular disease, bone and mineral disorders, and inflammation. The specific impacts of various probiotics on these CKD manifestations remain unexplored. This study delved into the potential of dietary probiotic interventions, particularly Bifidobacterium longum subsp. longum BL21, to modulate gut microbiota and mitigate metabolic disorders in a CKD rat model. Over a six-week period, we administered a dietary regimen of BL21 and conducted comprehensive analyses, including serum uremic toxin quantification and 16S rRNA gene sequencing, to systematically profile gut microbial alterations at the phylogenetic level. Our findings reveal that BL21 intervention significantly ameliorated CKD-induced disruptions in gut microbial populations, enhancing both microbial richness and the relative abundance of key taxa. Importantly, BL21 appeared to exert its beneficial effects by modulating the abundance of crucial species such as Barnesiella and Helicobacter. Functionally, the intervention markedly normalized serum levels of IS, IAA, and TMAO, while potentially attenuating p-cresol sulphate (PCS) and p-cresol glucuronide (PCG) concentrations. Consequently, BL21 demonstrated efficacy in regulating gut microbiota and curtailing the accumulation of uremic toxins. Our results advocate for the utilization of BL21 as a dietary intervention to diminish serum uremic toxins and re-establish gut microbiota equilibrium at the phylogenetic level, underscoring the promise of probiotic strategies in the management of CKD.

NIR-II light therapy improves cognitive performance in MPTP induced Parkinson's disease rat models: A preliminary experimental study

Cognitive impairment is an important component of non motor symptoms in Parkinson's disease (PD), and if not addressed in a timely manner, it can easily progress to dementia. However, no effective method currently exists to completely prevent or reverse cognitive impairment associated with PD. We therefore aimed to investigate the therapeutic effect of near-infrared region II light (NIR-II) region illumination on cognitive impairment in PD through behavioral experiments (water maze and rotary rod) and multiple fluorescence immunohistochemistry techniques. The 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced group was compared with the MPTP- untreated rat group, showing a significant reduction in escape latency and significant increase in the fall latency in the MPTP-treated group. The horizontal analysis results indicated that NIR-II phototherapy improved the learning and cognitive abilities as well as coordination and balance abilities of rats. Post-treatment, the MPTP rats showed significantly shortened, escape latency, prolonged target quadrant residence time, and prolonged fall latency compared with pre-treatment. The longitudinal analysis results reaffirmed that NIR-II phototherapy improved the learning and cognitive abilities as well as coordination and balance abilities of rats. The multiple fluorescence immunohistochemistry analysis trend plot showed that the activated microglia and astrocytes in the hippocampus were highest in MPTP-induced PD untreated group, moderate in MPTP-induced PD treatment group, and lowest in the control group. Our data indicates that NIR-II illumination improves learning and cognitive impairment as well as coordination and balance abilities in PD rats by downregulating the activation of microglia and astrocytes in the hippocampus.

Altered ECG parameters with loss of cardiac variability and prolonged QTc in a non-diabetic chronic kidney disease rat model

Altered ECG parameters with loss of cardiac variability and prolonged QTc in a non-diabetic chronic kidney disease rat model

Nutritional Approach to Ameliorate Demyelinating Changes Expressed in Spinal Olig2 Immunoreactivity in a Konzo Disease Rat Model

A nutritional approach to ameliorate demyelinating changes expressed in spinal Olig2 immunoreactivity in a Konzo disease rat model was investigated. 30 adult female Wistar rats weighing 200-250g were assigned to 4 groups. Group 1 (Control, n=5) was fed on animal pellets, whereas Group 2 (Protein control, n=5) was provided protein food. Bitter cassava flour was provided to Group 3 (Konzo induced, n=15). Protein and bitter cassava flour were supplied to Group 4 (protein treatment group, n=5). Body weight was taken weekly. The C3-C5 spinal regions were harvested through transcardiac perfusion for histological and immunohistochemical staining. Image J was used to quantify the cells in the spinal cord. Body weight showed a significant reduction in body weight in, Cassava at p<0.01, and Cassava + Protein group at p<0.05 when compared to the control and protein control groups. Examination of the neurons with cresyl violet showed a significant increase in the percentage of unhealthy neuron population in the Konzo-induced group [p<0.001] compared to the control and protein control groups. The rats induced with Konzo showed a significant decrease in Olig2 immunoreactive cells compared to control, protein control, and Cassava + protein groups, at p<0.05. Similarly, Olig2 immunoreactive was substantially increased in the Cassava + Protein group compared to the Cassava group [p<0.05]. This shows that an adequate diet, along with a protein supplement, can counteract the demyelinating and neurodegenerative effects of cyanogenic cassava consumption implicated in Konzo disease.

Neuroprotective effects of Anshen Bunao Syrup on cognitive dysfunction in Alzheimer's disease rat models

Alzheimer's disease (AD) presents a significant challenge due to its prevalence and lack of cure, driving the quest for effective treatments. Anshen Bunao Syrup, a traditional Chinese medicine known for its neuroprotective properties, shows promise in addressing this need. However, understanding its precise mechanisms in AD remains elusive. This study aimed to investigate Anshen Bunao Syrup's therapeutic potential in AD treatment using a scopolamine-induced AD rat model. Assessments included novel-object recognition and Morris water maze tasks to evaluate spatial learning and memory, alongside Nissl staining and ELISA analyses for neuronal damage and biomarker levels. Results demonstrated that Anshen Bunao Syrup effectively mitigated cognitive dysfunction by inhibiting amyloid-β and phosphorylation Tau aggregation, thereby reducing neuronal damage. Metabolomics profiling of rats cortex revealed alterations in key metabolites implicated in tryptophan and fatty acid metabolism pathways, suggesting a role in the therapeutic effects of Anshen Bunao Syrup. Additionally, ELISA and correlation analyses indicated attenuation of oxidative stress and immune response through metabolic remodeling. In conclusion, this study provides compelling evidence for the neuroprotective effects of Anshen Bunao Syrup in AD models, shedding light on its potential as a therapeutic agent for AD prevention and treatment.

SIRT1 regulates hepatic vldlr levels

BackgroundEndoplasmic reticulum (ER) stress-mediated increases in the hepatic levels of the very low-density lipoprotein (VLDL) receptor (VLDLR) promote hepatic steatosis by increasing the delivery of triglyceride-rich lipoproteins to the liver. Here, we examined whether the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1) regulates hepatic lipid accumulation by modulating VLDLR levels and the subsequent uptake of triglyceride-rich lipoproteins.MethodsRats fed with fructose in drinking water, Sirt1−/− mice, mice treated with the ER stressor tunicamycin with or without a SIRT1 activator, and human Huh-7 hepatoma cells transfected with siRNA or exposed to tunicamycin or different inhibitors were used.ResultsHepatic SIRT1 protein levels were reduced, while those of VLDLR were upregulated in the rat model of metabolic dysfunction-associated steatotic liver disease (MASLD) induced by fructose-drinking water. Moreover, Sirt1−/− mice displayed increased hepatic VLDLR levels that were not associated with ER stress, but were accompanied by an increased expression of hypoxia-inducible factor 1α (HIF-1α)-target genes. The pharmacological inhibition or gene knockdown of SIRT1 upregulated VLDLR protein levels in the human Huh-7 hepatoma cell line, with this increase abolished by the pharmacological inhibition of HIF-1α. Finally, SIRT1 activation prevented the increase in hepatic VLDLR protein levels in mice treated with the ER stressor tunicamycin.ConclusionsOverall, these findings suggest that SIRT1 attenuates fatty liver development by modulating hepatic VLDLR levels.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.

10 weeks low intensity treadmill exercise intervention ameliorates motor deficits and sustains muscle mass via decreasing oxidative damage and increasing mitochondria function in a rat model of Parkinson's disease

AimsParkinson's disease (PD) is characterized by loss of dopamine neurons in the brain, which leads to motor dysfunction; excessive inflammation induces neuronal death. This study aimed to determine the most effective exercise modality to improve motor dysfunction in PD by comparing three different exercise regimens (low-intensity treadmill, high-intensity treadmill, and swimming). Materials and methodsThe rat model for PD was established through stereotaxic surgery, inducing unilateral 6-OHDA (6-hydroxydopamine) lesions. The low-intensity treadmill regimen exerted better protective effects on neurological and motor functions in a rat model of unilateral 6-OHDA-induced PD compared to high-intensity treadmill and swimming. The most suitable exercise regimen and the optimal duration of daily exercise (15 or 30 min) on motor activity and oxidative stress parameters were evaluated. Key findingsComparison of 15 and 30 min low-intensity treadmill regimens (10 m/min) revealed 30 min daily exercise was the optimal duration and had more favorable impacts on neurological and motor function. Furthermore, we assessed the neuroprotective effects of exercising for 15 and 30 min per day for either four or ten weeks; 30 min of daily exercise for ten weeks improved mitochondrial function, the antioxidant defense system, neurotrophic factors, and muscle mass, and thereby provided protection against dopaminergic neuron loss, and motor dysfunction in rats with 6-OHDA-induced PD. Significance30 min of daily low-intensity treadmill exercise over 10 weeks resulted in heightened mitochondrial function in both muscle and brain tissues, therefore, yielded a neuroprotective effect against the loss of dopaminergic neurons and motor dysfunction in PD rats.

MST1 selective inhibitor Xmu-mp-1 ameliorates neuropathological changes in a rat model of sporadic Alzheimer's Disease by modulating Hippo-Wnt signaling crosstalk.

Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by progressive cognitive impairment accompanied by aberrant neuronal apoptosis. Reports suggest that the pro-apoptotic mammalian set20-like kinase 1/2 (MST1/2) instigates neuronal apoptosis via activating the Hippo signaling pathway under various stress conditions, including AD. However, whether inhibiting MST1/2 has any therapeutic benefits in AD remains unknown. Thus, we tested the therapeutic effects of intervening MST1/2 activation via the pharmacological inhibitor Xmu-mp-1 in a sporadic AD rat model. Sporadic AD was established in adult rats by intracerebroventricular streptozotocin (ICV-STZ) injection (3mg/kg body weight). Xmu-mp-1 (0.5mg/kg/body weight) was administered once every 48h for two weeks, and Donepezil (5mg/kg body weight) was used as a reference standard drug. The therapeutic effects of Xmu-mp-1 on ICV-STZ rats were determined through various behavioral, biochemical, histopathological, and molecular tests. At the behavioral level, Xmu-mp-1 improved cognitive deficits in sporadic AD rats. Further, Xmu-mp-1 treatment reduced STZ-associated tau phosphorylation, amyloid-beta deposition, oxidative stress, neurotoxicity, neuroinflammation, synaptic dysfunction, neuronal apoptosis, and neurodegeneration. Mechanistically, Xmu-mp-1 exerted these neuroprotective actions by inactivating the Hippo signaling while potentiating the Wnt/β-Catenin signaling in the AD rats. Together, the results of the present study provide compelling support that Xmu-mp-1 negated the neuronal dysregulation in the rat model of sporadic AD. Therefore, inhibiting MST/Hippo signaling and modulating its crosstalk with the Wnt/β-Catenin pathway can be a promising alternative treatment strategy against AD pathology. This is the first study providing novel mechanistic insights into the therapeutic use of Xmu-mp-1 in sporadic AD.

Hepatic-Metabolic Activity of α-Lipoic Acid-Its Influence on Sphingolipid Metabolism and PI3K/Akt/mTOR Pathway in a Rat Model of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Excessive lipid deposition affects hepatic homeostasis and contributes to the development of insulin resistance as a crucial factor for the deterioration of simple steatosis to steatohepatitis. So, it is essential to search for an effective agent for a new therapy for hepatic steatosis development before it progresses to the more advanced stages. Our study aimed to evaluate the potential protective effect of α-lipoic acid (α-LA) administration on the intrahepatic metabolism of sphingolipid and insulin signaling transduction in rats with metabolic dysfunction-associated steatotic liver disease (MASLD). The experiment was conducted on male Wistar rats subjected to a standard diet or a high-fat diet (HFD) and an intragastrically α-LA administration for eight weeks. High-performance liquid chromatography (HPLC) was used to determine sphingolipid content. Immunoblotting was used to measure the expression of selected proteins from sphingolipid and insulin signaling pathways. Multiplex assay kit was used to assess the level of the phosphorylated form of proteins from PI3K/Akt/mTOR transduction. The results revealed that α-LA decreased sphinganine, dihydroceramide, and sphingosine levels and increased ceramide level. We also observed an increased the concentration of phosphorylated forms of sphingosine and sphinganine. Changes in the expression of proteins from sphingolipid metabolism were consistent with changes in sphingolipid pools. Treatment with α-LA activated the PI3K/Akt/mTOR pathway, which enhanced the hepatic phosphorylation of Akt and mTOR. Based on these data, we concluded that α-lipoic acid may alleviate glucose intolerance and may have a protective influence on the sphingolipid metabolism under HFD; thus, this antioxidant appears to protect from MASLD development and steatosis deterioration.

Selenium nanoparticles decorated with polysaccharides from Sargassum fusiforme protects against 6-OHDA-induced neurotoxicity in PC12 cells and rat model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder and identifying disease-causing pathways and drugs that target them has remained challenging. Herein, selenium nanoparticles decorated with polysaccharides from Sargassum fusiforme (SFPS-SeNPs) were investigated on 6-OHDA-induced neurotoxicity in PC12 cells and rats. 6-OHDA can significantly increase neurotoxicity, oxidative stress and decrease the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) both in vitro and vivo. In vitro, treatment with SFPS-SeNPs can significantly decrease 6-OHDA cytotoxicity, reactive oxygen species (ROS) production or malondialdehyde (MDA) levels, and cell apoptosis, significantly increased the activity of SOD and GPx. In vivo, 6-OHDA exposure could also decrease the expression of Nrf2 and OH-1, while treatment with SFPS-SeNPs (1 mg Se/kg) increased. SFPS-SeNPs can protect neurons from 6-OHDA-induced neurotoxicity by regulating apoptosis and Nrf2/ARE pathway. The present study demonstrated that SFPS-SeNPs is a good candidate for developing a new drug against neurodegenerative diseases such as PD.

Niaodukang mixture inhibits micro-inflammation in CKD rats by enhancing MiR-146a levels in enterogenous exosomes

Ethnopharmacological relevanceThe Niaodukang mixture (NDK) is a preparation known for its ability to lower serum creatine levels in individuals with chronic kidney disease (CKD) and is commonly administered at medical facilities like the Zhongshan Hospital of Traditional Chinese Medicine. The initial use of NDK was mainly to treat CKD. Our hospital frequently utilizes NDK, which consists of Rheum officinaleBaill., Salvia miltiorrhiza Bunge., Astragalus aaronii (Eig) Zohary., Carthamus tinctorius L., and Sanguisorba officinalis L., for treating patients with CKD-MBD. It has the effects of eliminating dampness and turbidity and dredging kidney collaterals. However, The impact and process of NDK in chronic kidney disease remain unknown. Aim of the studyTo determine whether microRNA-146a (miR-146a) is associated with CKD micro-inflammationand whether NDK protects against CKD micro-inflammation by modulating the miR-146a/nuclear factor kappa-B (NF-κB) signaling pathway. Materials and methods(1) An adenine-induced rat model of chronic kidney disease was created through the use of materials and methods. The levels of miR-146a in exosomes from plasma and ileum were determined by RT-PCR. (2) Human cloned colon adenocarcinoma (Caco-2)cellswere stimulated with lipopolysaccharide (LPS)and transfected with miR-146a mimic and inhibitor. Following that, the Western blot and RT-PCR techniques were used to measure the protein and mRNA quantities of Toll-like receptor 4 (TLR4), NF-κB, and TNF receptor-associated factor 6 (TRAF6). (3) Enzyme-linked immunosorbent assay (ELISA) was used to identify serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). (4) Plasma exosomes were extracted, and the exosomes in intestinal tissues were extracted via ultrahigh-speed centrifugation.Negative staining electron microscopy was used to analyze the morphology of exosomes and the ultrastructure of intestinal tissue and exosomes. The particle size of the exosomes was measured using nanoparticle tracking analysis. ResultsThe pathological characteristics of CKD rats included those associated with systemic micro-inflammation, which may be associated with the release of exosomes in intestinal tissue. NDK suppressed the inflammatory response in Caco-2 cells and decreased the levels of IL-1β, IL-6, and TNF-α in rats with CKD. The expression of miR-146a, which regulates inflammation, differed between plasma-derived and enterogenous exosomes in CKD rats, which may be due to stimulation of ileal exosome release into the blood. NDK effectively reduced the levels of TRAF6, NF-κB, and TLR4 in the ileum tissue of CKD rats. ConclusionNDK can effectively improve micro-inflammation in CKD ratsby enhancing the release of enterogenous exosomes, thereby enhancing the release of exosome-associated miR-146a and inhibiting micro-inflammation.

Serum untargeted metabolomics analysis of the preventive mechanism of TAETEA Prebiotea on non-alcoholic fatty liver in rats

Pu-erh tea belongs to the six tea categories of black tea, according to the processing technology and quality characteristics, is divided into two types of raw tea and ripe tea. Raw tea is made from fresh leaves of tea as raw materials, through the process of greening, kneading, sun drying, steam molding and other processes made of tightly pressed tea. Ripe tea is made from Yunnan large-leafed sun green tea, using a specific process, post-fermentation (rapid post-fermentation or slow post-fermentation) processing of loose tea and tightly pressed tea. TAETEA Prebiotea is Puerh Ripe Tea, TAETEA Prebiotea has the effect of increasing insulin level and improving hyperglycemia in mice, and it also has the effect of regulating blood lipids, which can reduce the level of serum total cholesterol (TC) and triglycerides (TG), increase the level of high-density lipoprotein cholesterol (HDL-C), and improve the metabolism of lipids. Therefore, further experiments were conducted by us, and TAETEA Prebiotea was formulated into a suitable dose for the intervention of non alcoholic fatty liver disease (NAFLD) model rats, and at the end of the experiments, the samples of each group of experiments were analyzed and detected by the method of UHPLC-Q-Exactive LC-MS liquid-mass spectrometry methodology, and the relevant metabolites as well as metabolic pathways were analyzed by the method of Non targeted metabolomics analysis. As a result, 71 differential metabolites could be screened, of which 35 differential metabolites were up-regulated after intervention and 36 differential metabolites were down-regulated after intervention. Based on the KEGG pathway enrichment and Pathway Impact bubble diagram analysis, glycine, serine, threonine metabolism, arginine and proline metabolism, protein digestion and absorption, and central carbon metabolism in cancer may be the main metabolic pathways in which TAETEA Prebiotea exerted preventive effects on NAFLD rats, C00148 (Proline), C00300 (Creatine) and C00719 (Betaine) are the differential metabolites that play important regulatory roles.

Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery.

Strong precorneal clearance mechanisms including reflex blink, constant tear drainage, and rapid mucus turnover constitute great challenges for eye drops for effective drug delivery to the ocular epithelium. In this study, cyclosporine A (CsA) for the treatment of dry eye disease (DED) was selected as the model drug. Two strategies, PEGylation for mucus penetration and cationization for potent cellular uptake, were combined to construct a novel CsA nanosuspension (NS@lipid-PEG/CKC) by coating nanoscale drug particles with a mixture of lipids, DSPE-PEG2000, and a cationic surfactant, cetalkonium chloride (CKC). NS@lipid-PEG/CKC with the mean size ∼173 nm and positive zeta potential ∼+40 mV showed promoted mucus penetration, good cytocompatibility, more cellular uptake, and prolonged precorneal retention without obvious ocular irritation. More importantly, NS@lipid-PEG/CKC recovered tear production and goblet cell density more efficiently than the commercial cationic nanoemulsion on a dry eye disease rat model. All results indicated that a combination of PEGylation and cationization might provide a promising strategy to coordinate mucus penetration and cellular uptake for enhanced drug delivery to the ocular epithelium for nanomedicine-based eye drops.

Effects of Intravenously Administered Plasma from Exercise-Trained Donors on Microglia and Cytokines in a Transgenic Rat Model of Alzheimer's Disease.

Microglia and inflammation play a significant role in Alzheimer's disease (AD). Physical exercise and peripheral signals can influence microglial activity in the brain. Modulating the inflammatory response in the brain may provide therapeutic approaches for AD. To assess the effects of intravenously administered blood plasma from exercise-trained donor rats on cognitive function, microglia, and cytokine levels in an AD rat model at two different pathological stages; an early pre-plaque stage and a later stage closer to the emergence of extracellular plaques. Male transgenic McGill-R-Thy1-APP rats aged 2 and 5 months received 14 injections over 6 weeks: 1) plasma from exercise-trained rats (ExPlas), 2) plasma from sedentary rats (SedPlas), or 3) saline. Cognitive function was evaluated in a novel object recognition task. Microglia count and morphology were analyzed in cornu ammonis, dentate gyrus, entorhinal cortex, and subiculum. Amyloid plaque number and size were assessed in the rats with the later treatment start. A multiplex assay was used to measure 23 cytokines in cornu ammonis. In rats treated from 2 months of age, ExPlas and SedPlas increased number and length of microglial branches in cornu ammonis and dentate gyrus compared to saline. Only ExPlas-treated rats exhibited similar changes in subiculum, while entorhinal cortex showed no differences across treatments. Microglia count remained unaffected. In rats treated from 5 months of age, there were no significant differences in microglia count or morphology or the number or size of amyloid plaques in any brain region. Compared to both other treatments in early pre-plaque stage rats, SedPlas increased TNF-α levels. ExPlas upregulated GM-CSF, IL-18, and VEGF, while SedPlas increased IL-10 compared to saline. In later-stage rats, ExPlas upregulated IL-17, and SedPlas upregulated TNF-α compared to saline. There were no effects of treatments on recognition memory. Intravenous injections of blood plasma from exercise-trained and sedentary donors differentially modulated microglial morphology and cytokine levels in the AD rat model at an early pre-plaque stage of pathology. Exercised plasma may reduce proinflammatory TNF-α signaling and promote microglial responses to early Aβ accumulation but the lack of treatment effects in the later-stage rats emphasizes the potential importance of treatment timing.

Stereotactic surgery and its application in Alzheimer’s disease rat models

Stereotactic surgery is a technique that can be used to locate small targets in the body and administer interventions and/or treatments, such as injections, to the specific target. Stereotactic surgery is frequently used to create neurological disease models in experimental research in addition to clinical practice. The injection is administered with appropriate glass injectors using the rodent brain coordinate atlas after the specific brain region is determined. Alzheimer’s disease (AD), the most common cause of dementia, has no curative treatment yet. AD models can be created in rodents through stereotactic surgery and injections of different substances. These AD models represent the disease and are frequently used especially for drug development studies. AD-like models seem to examine different and unidirectional developmental mechanisms according to the creating way. However, AD is a multidirectional disease. AD rodent models created using different methods have specific properties. This review aims to explain the basic aspects of stereotactic surgery and to discuss AD rodent models created with this surgical technique and also with alternate methods.

The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease

Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated. This study aimed to assess the relationship between DA lesion, gait, and deficit-induced reversal with L-DOPA. To do so, Sprague–Dawley rats (N = 25, 14 males, 11 females) received unilateral medial forebrain bundle (MFB) DA lesions with 6-hydroxydopamine (6-OHDA). An automated gait analysis system assessed spatiotemporal gait parameters pre- and post-lesion, and after various doses of L-DOPA (0, 3, or 6 mg/kg; s.c.). The forepaw adjusting steps (FAS) test was implemented to evaluate lesion efficacy while the abnormal involuntary movements (AIMs) scale monitored the emergence of L-DOPA-induced dyskinesia (LID). High performance liquid chromatography (HPLC) assessed changes in brain monoamines on account of lesion and treatment. Results revealed lesion-induced impairments in gait, inclusive of max-contact area and step-sequence alterations that were not reversible with L-DOPA. However, the emergence of AIMs were observed at higher doses. Post-mortem, 6-OHDA lesions induced a loss of striatal DA and norepinephrine (NE), while prefrontal cortex (PFC) displayed noticeable reduction in NE but not DA. Our findings indicate that hemiparkinsonian rats display measurable gait disturbances similar to PD patients that are not rescued by DA replacement. Furthermore, non-DA mechanisms such as attention-related NE in PFC may contribute to altered gait and may constitute a novel target for its treatment.

Cacao consumption improves passive avoidance memory impairment in a rat model of Alzheimer's disease: the role of hippocampal synaptic plasticity and oxidative stress.

Introduction: Alzheimer's disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aβ). Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway-dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aβ plaques were detected in the hippocampal DG by performing Congo red staining. Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative-antioxidative status, and delayed Aβ plaques production in AD rats. Disscussion: Conclusively, cacao alleviates Aβ-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative-antioxidative status, and inhibition of Aβ plaque accumulation.