Aerobic exercise as a non-pharmacological approach to restless legs syndrome: Evidence from an ID-induced model.

Objective: To investigate the molecular mechanism of toll-like receptor adaptor protein SARM1 in glaucomatous optic neuropathy. Methods: The experimental study was conducted from February 2024 to October 2025. A chronic ocular hypertension glaucoma model was established by injecting micro-magnetic beads into the anterior chamber of 8- to 10-week-old male Wistar rats. At 3 days, 1 week, and 2 weeks post-modeling, retinal and optic nerve tissues from 6 eyes of 6 rats were collected as the chronic ocular hypertension glaucoma model group, and 6 eyes from 6 wild-type rats that received an equal volume of saline via anterior chamber injection served as the control group. Intraocular pressure was measured using a TonoLab tonometer. Retinal whole-mounts were prepared and POU domain class 4 transcription factor 1 (POU4F1 or Brn3A) immunofluorescence staining was used to detect retinal ganglion cell loss. Western blotting was performed to detect the expression levels of SARM1 and SNPH in the rat retina and optic nerve. Immunofluorescence staining was used to examine their distribution in these tissues. Furthermore, CRISPR/Cas9 technology was used to knock down the expression of SARM1 and SNPH in mouse 661W retinal ganglion cells, respectively. Cells were collected 48 hours after transfection, and Western blotting was performed to detect the expression levels of SARM1 and SNPH. Normally distributed continuous data are presented as mean±SEM. Comparisons between two groups were performed using the Student's t-test, while comparisons among multiple groups were assessed by the one-way analysis of variance followed by the Tukey's multiple comparisons test. Results: Western blot analysis revealed that in the glaucoma model group, the relative expression level of SARM1 protein in the optic nerve at one week post-modeling (1.22±0.06) was significantly higher than that in the control group (1.03±0.01; P=0.027, q=4.38). In contrast, the expression level of SARM1 in the retina at three days post-modeling (0.79±0.02) was significantly lower than that in the control group (1.04±0.03; P<0.001, q=6.86). Concurrently, the expression level of SNPH at three days post-modeling (0.74±0.01) was lower than that in the control group (1.03±0.04; P=0.040, q=0.58), and its expression at one week post-modeling (1.19±0.10; P=0.002, q=4.36) was significantly higher than that at three days (0.74±0.01). Consistent with the Western blot results, immunofluorescence staining results showed that in the optic nerve of the glaucoma model group, the expression of SARM1 was significantly higher than that in the control group at one week post-modeling, while the expression of SNPH was lower than that in the control group at three days post-modeling. Both proteins partially co-localized with the neuronal marker β3-tubulin. Immunofluorescence staining also revealed co-localization of these two proteins within axons. Additionally, SARM1 co-localized with the mitochondrial marker protein TOM20. Western blot results from 661W cells showed that the knockdown of SARM1 expression (0.54±0.04) significantly reduced SNPH expression (0.54±0.05; P=0.003, q=7.98), whereas the knockdown of SNPH expression (0.39±0.06) did not markedly affect SARM1 levels (0.75±0.05; P=0.010, q=6.39). Conclusion: The elevated expression of SARM1 protein in the axons of the rat glaucoma model can promote retinal ganglion cell axonal pathology by localizing to axonal mitochondria and regulating SNPH expression.

Clozapine-Induced parotid inflammation and the effect of N-Acetyl cysteine on it: An experimental study.

Dimethyl fumarate attenuates post-infarct myocardial injury and is associated with modulation of the NRG-1/ErbB2/Akt pathway and reduction of oxidative stress.

Temporal dynamics of cognitive and non-cognitive behavioral phenotypes and early redox alterations in the intracerebroventricular streptozotocin-rat model of sporadic Alzheimer's disease.

The hallmark of secondary spinal cord injury (SCI) is destruction of the blood-spinal cord barrier (BSCB). Nuclear heme oxygenase-1 (NHO-1) is involved in neuroprotection in the central nervous system. Previously, we demonstrated that adenoviral delivery of nuclear-targeted HO-1 (NHO-1) alleviates BSCB disruption, but the molecular mechanisms remain to be clarified. This study was conducted to investigate the specific regulatory mechanisms regulating tight junctions in the BSCB. A moderate T10 contusion SCI was induced in adult male Sprague-Dawley rats. Nuclear-targeted HO-1 was delivered by adenoviral pretreatment 7 days before injury. Spinal cords were collected at 24 h post-SCI for RNA-seq and quantitative real-time-PCR validation. BSCB permeability (Evans Blue), tight junction phosphorylation (western blot), and locomotor function (Basso, Beattie, and Bresnahan score and footprint analysis) were assessed, with intrathecal corticotropin-releasing hormone (CRH)-R1 agonist (Cortagine) or antagonist (Antalarmin) administered after SCI. RNA-seq identified 10 overlapping differentially expressed genes across pairwise comparisons; subsequent Venn-based prioritization and quantitative real-time-PCR validation identified Crh as the most consistently regulated candidate. Functional assays demonstrated that nuclear HO-1, particularly when combined with CRH receptor activation, decreased leakage of BSCB via enhancing phosphorylation of tight junction protein which disappears after application of CRH inhibitor. These results indicate that nuclear-targeted HO-1 promotes BSCB repair after SCI by transcriptionally upregulating Crh and enhancing CRH-dependent phosphorylation of tight junction proteins (Claudin-5 and Occludin).

To test the hypothesis that Alzheimer-like metabolic neurodegeneration rat model leads to an autonomic dysfunction, memory impairment, and hippocampal amyloid pathology and that long-term chemogenetic stimulation of the dorsal motor nucleus of the vagus reverses these alterations. Male and female transgenic Long Evans rats received intracerebroventricular streptozotocin to induce sporadic Alzheimer-like pathology. Cardiovascular parameters and sympathetic and parasympathetic tone were evaluated in conscious animals. Episodic-like memory was assessed using the novel object recognition test. Hippocampal amyloid density was quantified by immunofluorescence. In male rats, cholinergic neurons of the dorsal motor nucleus of the vagus were selectively activated for 15 days using a chemogenetic approach, and autonomic, cognitive, and neuropathological outcomes were reassessed. In male rats, the intracerebroventricular streptozotocin induced a significant increase in cardiac sympathetic tone, reduced object discrimination index performance, and increased hippocampal amyloid density compared with vehicle-treated controls, without altering mean arterial pressure or heart rate. Female rats showed no significant autonomic, memory, or hippocampal alterations at the same time point. Long-term chemogenetic stimulation of cholinergic neurons in the dorsal motor nucleus of the vagus in male rats reduced sympathetic tone to control levels, improved recognition memory, and attenuated hippocampal amyloid density compared with the non-stimulated control group. These findings demonstrate a link between autonomic imbalance, memory dysfunction, and hippocampal amyloid pathology, and selective stimulation of the dorsal motor nucleus of the vagus restores autonomic balance and improves episodic-like memory and neuropathological outcomes, identifying this brainstem nucleus as a physiologically relevant therapeutic target in Alzheimer-related neuropathology.

The immunomodulatory effect of chicoric acid on cyclophosphamide-mediated gonadal dysfunction in male rats: Cross-talk between sirtuin-1, HMGB1/RAGE/TLR4 axis, and PI3K/Akt/mTOR signaling.

There are age and sex differences in the processing of social reward, although the basis for these differences is not well established. We previously found greater social motivation at P50 (postpubertal adolescence) than at P70 (adulthood), and that female rats showed greater social motivation than male rats. Thus, we investigated whether gonadal hormones may contribute to age and sex differences in social reward motivation. Rats underwent either gonadectomy or sham surgery at P41 (adolescent group) or P69 (adult group) and began testing in the operant conditioning paradigm 5days later. When trained on a fixed ratio of one, gonadectomized rats had a greater social preference relative to control rats, irrespective of sex and age. When tested on a progressive ratio (effort required to access social reward continually increased), adolescents were more motivated than were adults, irrespective of sex or gonadal status. However, resistance to extinction was evident in gonadectomized rats relative to control rats, irrespective of sex and age. Thus, the results provide evidence that gonadal hormones influence social preference, although not social motivation. Ongoing maturation, rather than puberty, is responsible for age-related changes in social reward motivation, and the presence of gonadal hormones independently influences the preference for a social partner.

Sex-specific effects of chronic electrical acustimulation and sacral nerve stimulation in a rodent model of irritable bowel syndrome.

This study investigates the mechanism of the TRPV1 channel in neuropathic pain (NP), focusing on the c/EBPβ/Uchl3/TRPV1 axis and mitochondrial dynamics. Using male rats chronic constriction injury (CCI) model and an LPS-induced dorsal root ganglion (DRG) cell model, we measured paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL), assessed expression changes of related molecules via Real-time quantitative reverse transcription PCR (RT-qPCR) and Western blot, observed mitochondrial fission via transmission electron microscopy (TEM) and Tomm20 immunofluorescence, evaluated mitochondrial function via JC-1 and MitoSOX, and examined neuronal excitability via calcium imaging. Co-immunoprecipitation (Co-IP) confirmed Uchl3-TRPV1 binding, and ubiquitination assay combined with Cycloheximide (CHX) chase and proteasome inhibition assays demonstrated that Uchl3 inhibits TRPV1 degradation via deubiquitination. Luciferase and Chromatin immunoprecipitation (ChIP) assays verified c/EBPβ as a transcriptional activator of Uchl3. Results showed that TRPV1 activation promoted mitochondrial fission, dysfunction, and neuronal excitability, driving NP. Uchl3 stabilized TRPV1 by removing its ubiquitination, altering mitochondrial dynamics. c/EBPβ transcriptionally upregulated Uchl3, forming a regulatory cascade. Intrathecal si-c/EBPβ in CCI rats downregulated c/EBPβ, Uchl3, and TRPV1, restored mitochondrial homeostasis, and alleviated pain behavior. In conclusion, the c/EBPβ/Uchl3/TRPV1 pathway regulates NP through mitochondrial dynamics in male rats, presenting a novel therapeutic target for NP treatment.

Exposure to sexual stimuli induces specific changes of dendritic spine in the prefrontal and accumbens regions of naïve and sexually-experienced male rats.

Bacopa monnieri confers neuroprotection against middle cerebral artery occlusion (MCAO)-induced neurobehavioral and biochemical dysregulation in the frontal cortex and hippocampus of male Wistar rats.

Therapeutic effect of cilastatin administration in LPS-induced retinotoxicity.

Cerebrovascular dysfunction, including reduced cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), contributes to Alzheimer's disease (AD). Caloric restriction (CR) and resveratrol (Rsv) benefit vascular health, yet their impact on CBF and CVR in AD remains unclear. Here, we investigated the cerebrovascular effects of 40% CR or Rsv supplementation in WT and TgF344-AD rats. Using pseudo-continuous arterial spin labelling (pCASL) MRI, we observed that male Tg control (Ctrl) rats exhibited reduced relative CBF (rCBF) and absolute CBF (aCBF) in the caudate-putamen at baseline compared to WT Ctrl and Tg Rsv rats, while Rsv restored CBF to WT levels. Male Rsv rats also showed higher rCBF than CR rats in the somatosensory cortex, irrespective of genotype. In the cingulate cortex, male Tg rats had lower rCBF than WT, irrespective of treatment. During hypercapnia, Tg males displayed lower rCBF and aCBF across multiple regions, while Rsv increased rCBF in cingulate cortex and somatosensory cortex, regardless of genotype. In females, treatments did not affect baseline or hypercapnic CBF, although CR and Rsv reduced CVR compared to Ctrl. In summary, these findings suggest Rsv reverses AD-related hypoperfusion in males, whereas CR may impair cerebrovascular responsiveness in females, highlighting the need for sex-specific therapeutic strategies.

Carbon monoxide and anti-amyloid-β combination therapy modulates miR-381 and molecular biomarkers in an aluminum chloride-induced rat model of Alzheimer's disease.

The southern giant pouched rat (Cricetomys ansorgei) is a large rodent utilised in recognition of landmines, pulmonary tuberculosis and Brucella infection. Additionally, they are kept as pet animals. The aim of this study was to describe the radiological anatomy of the pelvis and hind limb and to provide measurements of the hind limb bones in southern giant pouched rats. Radiological examinations were performed in 10 live and five dead adult southern giant pouched rats. The pelvis had a relatively short pelvic symphysis and the ischial tuberosities were less prominent. The obturator foramina and cranial opening of the pelvis had a pear-shape. The proximal extremity of the femur had well-developed major, minor and third trochanters, with the major trochanter extending higher than the femoral head. All rats had medial and lateral fabellae. Ossicles of the menisci were visualised. The mineralised popliteal sesamoid bone was not seen. Tibia and fibula were fused in the distal third of the crus. Seven tarsal bones were seen and the tarsal sesamoid bone was present in all rats. Five slender metatarsal bones and digits were present. The os penis was seen in all male rats. The tibia was the longest bone of the hind limb. This study has provided the radiological anatomy of the pelvis and hind limb of the southern giant pouched rat. Information from this study will be beneficial to anatomists, clinicians and students in more understanding of the functional anatomy of the pelvis and hind limb of southern giant pouched rats.

Cardiac mitochondrial dysfunction is a crucial mechanism underlying obesity-induced cardiovascular diseases. A close link between obesity and gut microbiota has been revealed, and the benefits of gut microbiota modulation by probiotics have been widely identified. Although the probiotic Lactobacillus reuteri KUB-AC5 exerted anti-inflammatory activity and enhanced the activity of beneficial microbes, the effects of this probiotic on mitochondria in the obese heart have never been investigated. Male Wistar rats were divided into four groups to receive either a normal diet (ND; n = 9) or a high-fat and high-calorie diet (HFCD; n = 30) for 24 weeks. At the beginning of week 13, ND-fed rats received vehicle, while HFCD-fed rats were further subdivided into three groups (n = 10/group) to receive either vehicle, a live probiotic Lactobacillus reuteri KUB-AC5, or a heat-killed probiotic Lactobacillus reuteri KUB-AC5. At the end of week 24, cardiac functions were evaluated. The rats were then euthanized to enable blood and cardiac ventricle collection. Evidence from the obese rats treated with Lactobacillus reuteri KUB-AC5 in both forms indicated reduced body weight and attenuated insulin resistance. Regarding the heart, obese rats treated with either form of Lactobacillus reuteri KUB-AC5 had improved cardiac functions, mitochondrial dynamics, mitochondrial biogenesis, fat and ketone body utilization, anaplerosis, ATP production, and oxidative phosphorylation. In addition, treatment with this probiotic diminished oxidative stress and restored the antioxidative capacity of cardiac mitochondria. Our preclinical findings in male rats highlighted the benefits of the probiotic Lactobacillus reuteri KUB-AC5, given in both live and heat-killed forms, in alleviating obesity-induced cardiac mitochondrial dysfunction.

Vitamin D as an adjunctive therapy in orthodontics: Impact on alveolar bone and root resorption in male rats.

This study aimed to develop and validate an atherosclerosis-induced chronic bladder ischemia (CBI) model in female rats and to evaluate mechanosensitive single-unit afferent activity (SAA) in bladder-innervating fibers in both male and female CBI models. Sprague-Dawley rats of both sexes were divided into sham and CBI groups. The CBI group underwent balloon-induced endothelial injury of the iliac arteries and received a 2% cholesterol diet for 8 weeks. Sham rats underwent bilateral inguinal incisions without arterial injury and were fed a regular diet. In female rats, iliac arterial wall thickening, 24-h voiding behavior, cystometric parameters, bladder blood flow, and fibrosis were assessed to evaluate CBI-induced bladder dysfunction. SAAs were recorded under urethane anesthesia. Bladder-innervating fibers were identified via electrical stimulation of the left pelvic nerve and bladder distension. Fibers were classified as Aδ- or C-fibers based on conduction velocity. Female CBI rats showed thickening of the common iliac arteries, increased voiding frequency, shortened intercontraction intervals, reduced bladder blood flow, and detrusor smooth muscle fibrosis, consistent with previous studies in male rats. In both sexes, the CBI group showed significantly higher SAAs in C-fibers than the sham group. No significant differences were found in SAAs of Aδ-fibers, although there was a tendency for female CBI rats to show higher activity. This study successfully established arteriosclerosis-induced CBI accompanied by frequent voiding in female rats, similar to males. In addition, the present findings suggest that C-fiber, but not Aδ-fiber, afferent activity is selectively facilitated under CBI conditions.