Rat Model Of Disease Research Articles

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein.

Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson's disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca+/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca+/+ rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes. However, only LPS Snca+/+ rats showed dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), associated with a reduction in the release of evoked dopamine in the striatum. No significant changes were observed in the behavioral domain. We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD.

Antidepressive and cardioprotective effects of Kai-xin-san via the regulation of HPA axis dysfunction and lipid metabolism in a rat model of depressive-cardiac disease

Depressive-cardiac disease is a comorbid state in which both cardiovascular diseases and mental disorders are present. Patients with depression are more likely to develop cardiovascular disease, which increases the risk of cardiovascular events, such as acute coronary syndrome. Cardiovascular diseases also exacerbate the poor mood of patients with psychiatric disorders. Kai-xin-san (KXS), a classic antidepressant formula, has potential antidepressive and cardioprotective effects. In the present study, we first evaluated the antidepressive and cardioprotective effects of KXS in two post-myocardial ischemic depressed rat models: a) isoproterenol (ISO) via intraperitoneal injection combined with chronic unpredictable mild stress (CUMS)-induced myocardial ischemia and depression and b) left anterior descending coronary artery ligation (LAD) combined with chronic restraint stress (CRS)-induced myocardial ischemia and depression. We then induced exogenous corticosterone in a rat model of depressive-cardiac disease. Our study revealed that chronic administration of corticosterone could induce depression-like syndromes accompanied by cardiac insufficiency. The potential mechanism involves parallel onset of HPA axis dysfunction and an imbalance in lipid metabolism. KXS treatment successfully reversed corticosterone-induced depression-like behaviors and cardiac insufficiency. The present study highlights the pivotal role of the HPA axis and lipid metabolism in the development of comorbid depression and cardiovascular disease. Thus, KXS could be a promising therapeutic option for depressive-cardiac disease.

Ambroxol Improves Amyloidogenic, NF‐κB, and Nrf2 Pathways in a Scopolamine‐Induced Cognitive Impairment Rat Model of Alzheimer's Disease

ABSTRACTAmbroxol (ABX) is used to manage excessive production of mucus in the respiratory system. The present study sought to assess the neuroprotective potential of ambroxol by influencing the amyloidogenic, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and nuclear factor erythroid 2‐related factor 2 (Nrf2) pathways in a rat model of Alzheimer's disease (AD) induced by scopolamine. The AD pathology was induced by chronic administration of scopolamine. The rats were given scopolamine at a dose of 2 mg/kg via intraperitoneal injection daily for 14 days, followed by treatment (ABX 121.5, 135, and 180 mg/kg orally and 5 mg/kg orally of donepezil) for the next 28 days while continuing to receive daily scopolamine injection. The behavior of the rats was evaluated using Modified Y‐Maze and Novel object recognition tasks. Analyses were carried out on AD pathological markers [Amyloid beta peptide 1‐40, Amyloid beta peptide 1‐42, acetylcholinesterase, beta‐secretase 1 (BACE1), total tau, and p‐tau], inflammatory markers [NF‐κB, tumor necrosis factor alpha (TNF‐α), interleukin 6 (IL‐6), and interferon γ], antioxidant markers (Nrf2 and heme Oxygenase 1 (HO‐1)], along with synaptophysin and glial fibrillary acidic protein (GFAP) immunohistochemistry and histopathological assessment of the hippocampus. Our findings indicated that ABX reduced impairment in behavior. Levels of Acetylcholinesterase, BACE1, amyloid beta 1‐40, amyloid beta 1‐42, total tau, p‐tau, NF‐κB, IFN‐γ, IL‐6, and TNF‐α decreased significantly. There was a significant increase in the levels of HO‐1 and Nrf2. It stopped the neuronal degeneration, raised synaptophysin immunoreactivity, and lowered GFAP immunoreactivity. The current research indicates that ambroxol may possess senomorphic properties by impacting the transcription factors NF‐κB and senescence‐associated secretory phenotype (SASP). Consequently, it could provide neuroprotection through alterations in the Nrf2 and NF‐κB signaling pathways in AD.

Retracted] Brain cell apoptosis inhibition by butylphthalide in Alzheimer's disease model in rats.

[This retracts the article DOI: 10.3892/etm.2017.4322.].

Intranasal AdipoRon Mitigated Anxiety and Depression-Like Behaviors in 6-OHDA-Induced Parkinson 's Disease Rat Model: Going Beyond Motor Symptoms.

Depression and anxiety are prevalent neuropsychiatric conditions among patients with Parkinson's disease (PD), which may manifest prior to motor symptoms. As levodopa, a prominent treatment for PD motor symptoms, provides few benefits for mood-related abnormalities, tackling non-motor symptoms is particularly important. AdipoRon (Ad), an adiponectin agonist, has demonstrated neuroprotective effects by suppressing neuroinflammatory responses and activating the AMPK/Sirt-1 signaling pathway. This study looked at the potential advantages and underlying mechanisms of intranasal Ad in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). We found that Ad at doses of 1 and 10µg for 21 days exhibited anxiolytic- and antidepressant effects in the open field (OF) test, elevated plus maze (EPM), sucrose splash test, and forced swimming test in a PD model caused by a unilateral 6-OHDA injection into the medial forebrain bundle (MFB). The Ad also lowered the levels of corticosterone in the blood, decreased inflammasome components (NLRP3, caspase 1, and IL-1β), and increased Sirt-1 protein levels in the prefrontal cortex (PFC) of PD rats. We conclude that Ad ameliorates anxious and depressive-like behaviors in the PD rat model through stimulating the AMPK/Sirt-1 signaling and blocking the NLRP3 inflammasome pathways in the PFC.

Dopamine D4 receptors in the lateral habenula regulate anxiety-related behaviors in a rat model of Parkinson's disease

Although the output of the lateral habenula (LHb) controls the activity of midbrain dopamine (DA) and 5-hydroxytryptamine (5-HT) containing systems, which are implicated in the pathophysiology of anxiety, it is not clear how activation and blockade of LHb D4 receptors affects anxiety-like behaviors, particularly in Parkinson’s disease related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) in rats induced anxiety-like behaviors, which attribute to hyperactivity of LHb neurons and decrease in the level of DA in the medial prefrontal cortex (mPFC), amygdala and ventral hippocampus (vHip) compared to sham-operated rats. Intra-LHb injection of D4 receptor agonist A412997 induced or increased the expression of anxiety-like behaviors, while injection of D4 receptor antagonist L741742 showed anxiolytic effects in sham-operated and the SNc-lesioned rats. However, the doses producing behavioral effects in the lesioned rats were higher than those of sham-operated rats. Intra-LHb injection of A412997 increased firing rate of LHb neurons, and decreased levels of DA and 5-HT in the mPFC, amygdala and vHip; conversely, L741742 decreased firing rate of LHb neurons, and increased levels of DA and 5-HT in two groups of rats. Compared to sham-operated rats, the duration of A412997 and L741742 action on the firing rate of neurons was markedly shortened in the lesioned rats. Collectively, these findings suggest that D4 receptors in the LHb are involved in the regulation of anxiety-like behaviors, and degeneration of the nigrostriatal pathway down-regulates function and/or expression of these receptors.

Melatonin and Hydrogen Sulfide ameliorates cognitive impairments in Alzheimer's disease rat model exposed to chronic mild stress via attenuation of neuroinflamation and inhibition of oxidative stress: Potential role of BDNF

Melatonin and Hydrogen Sulfide ameliorates cognitive impairments in Alzheimer's disease rat model exposed to chronic mild stress via attenuation of neuroinflamation and inhibition of oxidative stress: Potential role of BDNF

Brain-Region-Specific Differences in Protein Citrullination/Deimination in a Pre-Motor Parkinson's Disease Rat Model.

The detection of early molecular mechanisms and potential biomarkers in Parkinson's disease (PD) remains a challenge. Recent research has pointed to novel roles for post-translational citrullination/deimination caused by peptidylarginine deiminases (PADs), a family of calcium-activated enzymes, in the early stages of the disease. The current study assessed brain-region-specific citrullinated protein targets and their associated protein-protein interaction networks alongside PAD isozymes in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Six brain regions (cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb) were compared between controls/shams and the pre-motor PD model. For all brain regions, there was a significant difference in citrullinated protein IDs between the PD model and the controls. Citrullinated protein hits were most abundant in cortex and hippocampus, followed by cerebellum, midbrain, olfactory bulb and striatum. Citrullinome-associated pathway enrichment analysis showed correspondingly considerable differences between the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways identified in PD brains only were associated with neurological, metabolic, immune and hormonal functions and included the following: "Axon guidance"; "Spinocerebellar ataxia"; "Hippo signalling pathway"; "NOD-like receptor signalling pathway"; "Phosphatidylinositol signalling system"; "Rap1 signalling pathway"; "Platelet activation"; "Yersinia infection"; "Fc gamma R-mediated phagocytosis"; "Human cytomegalovirus infection"; "Inositol phosphate metabolism"; "Thyroid hormone signalling pathway"; "Progesterone-mediated oocyte maturation"; "Oocyte meiosis"; and "Choline metabolism in cancer". Some brain-region-specific differences were furthermore observed for the five PAD isozymes (PADs 1, 2, 3, 4 and 6), with most changes in PAD 2, 3 and 4 when comparing control and PD brain regions. Our findings indicate that PAD-mediated protein citrullination plays roles in metabolic, immune, cell signalling and neurodegenerative disease-related pathways across brain regions in early pre-motor stages of PD, highlighting PADs as targets for future therapeutic avenues.

Changes in Skeletal Muscle Atrophy over Time in a Rat Model of Adenine-Induced Chronic Kidney Disease

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. The back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA was recovered at 20 weeks. SDH staining was lower in CKD than in control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time.

Effects of dopaminergic neuron degeneration on osteocyte apoptosis and osteogenic markers in 6-OHDA male rat model of Parkinson's disease

Parkinson's disease (PD) and osteoporosis are prevalent chronic conditions that impact a significant proportion of the aging population. Observational and longitudinal studies consistently demonstrate that individuals with PD face an elevated risk of osteoporosis and reduced bone mineral density compared to control groups. However, there is currently no experimental evidence demonstrating the impact of dopaminergic neuron degeneration on bone metabolism. In the present study, we used a male rat model of PD induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the left medial forebrain bundle (MFB) to evaluate the effect of dopaminergic neuron lesion on certain parameters of bone metabolism. To confirm the dopaminergic neuron lesion, cylinder and Rotarod tests were applied to rats injected with 6-OHDA or vehicle. Osteocyte density and viability were determined through histology and TUNEL assay. Western Blot and immunohistochemistry analysis were performed to investigate whether dopaminergic degeneration influences the expression of some apoptotic markers (Caspase 3 and Cytochrome C) and some osteogenic markers (ALP, OCN, and RUNX2). Our findings show that the dopaminergic lesion resulting from the injection of 6-OHDA was successfully confirmed through behavioral tests. Furthermore, the degeneration of dopaminergic neurons induced by 6-OHDA leads to apoptosis of osteocytes associated with a significant reduction in the tissue expression of the studied osteogenic markers. Thus, our study provides evidence that 6-OHDA-induced degeneration of dopaminergic neurons leads to osteocyte apoptosis, which may contribute to the development of some signs of osteoporosis.

Integrating fecal metabolomics and gut microbiome to reveal the mechanism of Schisandra chinensis-Acorus tatarinowii Schott treatment in Alzheimer’s disease rats

BackgroundSchisandra chinensis (Turcz.) Baill (Schisandraceae) and Acorus tatarinowii Schott (Araceae Juss) (Sc-At) are two traditional Chinese medicinal herbs that are widely used in the treatment of neurological disorders such as insomnia. In our previous study, we found that Sc-At could improve the therapeutic efficacy of Alzheimer’s disease by affecting aromatase activity and estrogen levels, among other pathways. Material and methodsIn this study, first, the ameliorative effect of Sc-At on cognitive dysfunction in Alzheimer’s disease model rats was verified by Y-maze test together with Elisa assay. Second, fecal untargeted metabolomics analysis was performed using a UPLC-Q-TOF/MS-based metabolomics approach. 16S rDNA sequencing was utilized to screen the differential flora between groups, and linear discriminantan alysis effect size (LEfSe) was used to find the target flora. Finally, Spearman correlation analysis was combined to find the relationship between differential flora and differential metabolites in feces. Results(1) The results of Y-maze test and Elisa assay indicated that Sc-At could improve the cognitive dysfunction of AD model rats. (2) Metabolomics results showed that fecal metabolite levels were significantly different from those of rats in the blank group, and 18 potential biomarkers in feces were screened, mainly affecting linoleic acid metabolism, steroid hormone biosynthesis, sphingomyelin metabolism, riboflavin metabolism, etc. The 16S rDNA results showed that the abundance and diversity of intestinal flora in AD rats were destroyed, and the Sc-At treatment was able to reverse these changes. (3) Spearman’s correlation analysis showed a significant correlation between differential metabolites in feces and intestinal flora, further suggesting that Sc-At treats Alzheimer’s disease through the gut-brain axis. ConclusionsIn this study, we explored the mechanism of Sc-At in the treatment of Alzheimer’s disease by integrating fecal untargeted metabolomics and 16S rDNA gene sequencing, and the results showed that Sc-At exerts therapeutic effects on Alzheimer’s disease by improving the intestinal flora and related metabolic pathways.

Modulation of Kidney Disorders in Type 2 Diabetes: Evaluating the Role of Probiotics in a Rat Model of Diabetic Kidney Disease

Modulation of Kidney Disorders in Type 2 Diabetes: Evaluating the Role of Probiotics in a Rat Model of Diabetic Kidney Disease

Three-Dimensional Imaging and Genetic Characterisation of a Rat Model of Polycystic Kidney Disease

Three-Dimensional Imaging and Genetic Characterisation of a Rat Model of Polycystic Kidney Disease

Network Pharmacology and Experimental Verification: SanQi-DanShen Treats Coronary Heart Disease by Inhibiting the PI3K/AKT Signaling Pathway.

To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease. We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin. Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue. Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.

A Single-Cell Atlas of the Substantia Nigra Reveals Therapeutic Effects of Icaritin in a Rat Model of Parkinson's Disease.

Degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain are the main pathological changes in Parkinson's disease (PD); however, the mechanism underlying the selective vulnerability of specific neuronal populations in PD remains unclear. Here, we used single-cell RNA sequencing to identify seven cell clusters, including oligodendrocytes, neurons, astrocytes, oligodendrocyte progenitor cells, microglia, synapse-rich cells (SRCs), and endothelial cells, in the substantia nigra of a rotenone-induced rat model of PD based on marker genes and functional definitions. We found that SRCs were a previously unidentified cell subtype, and the tight interactions between SRCs and other cell populations can be improved by icaritin, which is a flavonoid extracted from Epimedium sagittatum Maxim. and exerts anti-neuroinflammatory, antioxidant, and immune-improving effects in PD. We also demonstrated that icaritin bound with transcription factors of SRCs, and icaritin application modulated synaptic characterization of SRCs, neuroinflammation, oxidative stress, and survival of dopaminergic neurons, and improved abnormal energy metabolism, amino acid metabolism, and phospholipase D metabolism of astrocytes in the substantia nigra of rats with PD. Moreover, icaritin supplementation also promotes the recovery of the physiological homeostasis of the other cell clusters to delay the pathogenesis of PD. These data uncovered previously unknown cellular diversity in a rat model of Parkinson's disease and provide insights into the promising therapeutic potential of icaritin in PD.

The Study of the Biologically Active Effect of the Rubia Tinctorum L. Plant on Rats with Experimental Kidney Stone Disease and Issues of Introduction

Since ancient times, madder dye (Rubia tinctorum L.) has been used in Uzbekistan to help alleviate stone deposits in organs. In the experiment we conducted, we aimed to demonstrate that this plant can prevent the occurrence of kidney stone disease in rats using an induced model of the disease. The kidney stone disease model in rats was created by administering ethylene glycol and ammonium chloride to the animals over a period of 10 days. The substances contained in the madder dye plant mitigated the effects of the substances used to induce the disease. According to the study results, simultaneous oral administration of the madder dye extract prevented the development of kidney stone disease in rats. The extract of Rubia tinctorum L. was found to be highly effective, showing a significant nephroprotective effect due to its specific and rich composition of terpenes and terpenoids.

Diosgenin ameliorating non-alcoholic fatty liver disease via Nrf2-mediated regulation of oxidative stress and ferroptosis.

This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non-alcoholic fatty liver disease, focusing particularly on ferroptosis-related pathways and its reliance on nuclear factor erythroid 2-related factor 2. Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis-related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin-1β and tumour necrosis factor-α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high-fat diet-induced non-alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2-related factor 2 and its downstream ferroptosis-related genes to inhibit ferroptosis in the livers of rats with non-alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis-related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2-related factor 2. This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2-related factor 2 regulation, offering novel insights into the treatment of non-alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine.

L‐arginine mitigates choroid plexus changes in Alzheimer’s disease rat model via oxidative/inflammatory burden and behavioral modulation

Aging is a risk factor for Alzheimer’s disease (AD), leading to choroid plexus (CP) alterations. This study aimed to explore the possible therapeutic mechanisms of ARG on AD-induced CP changes. Sprague-Dawley rats were divided into 6 groups (n = 7 per group): adult, adult+ARG, aged, aged+ARG, aged+AD, and aged+AD+ARG groups. Evaluations were for Y-maze test, serum levels of oxidative/inflammatory markers, and serum and cerebrospinal fluid (CSF) markers of AD, histopathology, immunohistochemistry, and histomorphometry. The aged+AD group demonstrated a significant decline in maze test parameters, total antioxidant capacity (TAC), brain-derived neurotrophic factor (BDNF) levels, and vascular endothelial growth factor (VEGF) immunoexpression, while tumour necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), beta-amyloid (Aβ) levels and amyloid protein precursor (APP), and heat shock protein90 (HSP90) immunoexpressions were significantly increased. Sections of this group showed flat epitheliocytes, congested capillaries, connective tissue expansion, and degenerated endothelium. These parameters were modulated by ARG administration, via increased levels of TAC (1.37 vs 2.17 mmol/L), (p = 0.018) BDNF (serum: 48.50 vs 78.41; CSF: 4.07 vs 7.11 pg/ml) (p< 0.001), and VEGF (0.07 vs 0.26 OD) (p< 0.001), in addition to decreased levels of TNF-α (86.63 vs 41.39 pg/ml) (p< 0.001), IL-1β (96.04 vs 39.57 pg/ml) (p< 0.001), Aβ (serum: 67.40 vs 47.30; CSF: 189.26 vs 169.84 pg/ml) (p< 0.001), and HSP90 (0.54 vs 0.13 OD) (p< 0.001). In conclusion, ARG ameliorates the AD-associated CP changes, including histopathological, oxidative/inflammatory, and AD markers, and VEGF and HSP90 immunohistochemical alterations. Dietary ARG consumption is recommended to avoid AD progression in the elderly.

Methods for Establishing a Rat Model of Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is responsible for nearly 250,000 deaths annually and poses a significant health threat in developing areas. The unclear pathogenesis of RHD makes the development of cost-effective treatments challenging, particularly as current surgical options are expensive and technologically demanding, exacerbating the economic and quality-of-life burdens for patients. Given the risks associated with direct human experimentation due to the uncertain pathogenesis, using a rat model infected with Group A Streptococcus (GAS) has become a crucial experimental strategy for RHD research. The development of an RHD rat model, refined over 23 years, now stands as a pivotal approach in studies aiming to understand the disease's pathogenesis. This review summarizes the evolution, characteristics, advantages, and limitations of the RHD rat model, offering insights into potential areas for improvement. It aims to provide researchers with a comprehensive understanding of the model, supporting the advancement of research methodologies and the discovery of innovative treatments for RHD.

Novel insights into famotidine as a GSK-3β inhibitor: An explorative study in aluminium chloride-induced Alzheimer’s disease rat model

Alzheimer's disease (AD), a chronic neurodegenerative disease, presents a substantial global health challenge. This study explored the potential therapeutic role of famotidine, a histamine (H2) receptor antagonist, as a glycogen synthase kinase-3β (GSK-3β) inhibitor in the context of AD induced by aluminium chloride (AlCl3) in a rat model. The intricate relationship between GSK-3β dysregulation and AD pathogenesis, particularly in amyloid-β (Aβ) production, formed the basis for investigating famotidine's efficacy. Molecular modelling revealed famotidine's efficient binding to GSK-3β, suggesting inhibitory potential. In behavioural assessments, famotidine-treated groups exhibited dose-dependent improvements in Morris Water Maze, Novel Object Recognition, and Y-Maze tests, comparable to the standard Rivastigmine tartrate group. Biochemical analyses showed that famotidine inhibits acetylcholinesterase, decreases lipid peroxidation, increases antioxidant activity, and mitigates oxidative stress. Moreover, famotidine significantly lowered the levels of GSK-3β, IL-6, and Aβ(1−42). The neuroprotective effects of famotidine were further supported by histopathological analysis. This comprehensive investigation underscores famotidine's potential as a GSK-3β inhibitor, providing insights into its therapeutic impact on AD induced by AlCl3. The study offers a promising avenue for repurposing famotidine due to its established safety profile and widespread availability, highlighting its potential in addressing the formidable challenge of AD.