Young Rats Research Articles

The effect of eight weeks of high-intensity interval training on the expression of mir-126, EMAP-II, and levels of TGF-β in the heart tissue of young rats with type 2 diabetes

Background and aims: Diabetes affects some cardiac angiogenic and antiangiogenic markers. Thus, the aim of this study was to investigate the effect of eight weeks of high-intensity interval training (HIIT) on mir-126, endothelial monocyte-activating polypeptide II (EMAP-II), and transforming growth factor beta (TGF-β) in young rats with type 2 diabetes (T2D). Methods: The statistical population of this experimental study included young rats (8 weeks old) with T2D. In this research, 24 young rats (8 weeks old) were divided into healthy+HIIT, diabetic+HIIT, and healthy control groups. The enzyme-linked immunosorbent assay method was used to measure TGF-β and the real-time polymerase chain reaction for mir-126 and EMAP-II. A one-way analysis of variance and the least significant difference post hoc test were used to compare the two groups. Results: The results showed diabetes+HIIT and healthy+HIIT had more mir-126 compared to healthy control (P=0.001). Healthy+HIIT, in comparison to diabetes+HIIT, had higher mir-126 expression (P=0.001). In addition, diabetes+HIIT, compared to the healthy control, had a higher EMAP-II expression (P=0.006). On the other hand, healthy+HIIT had lower EMAP-II in comparison to healthy control (P=0.001). Healthy+HIIT had a lower EMAP-II compared to diabetes+HIIT (P=0.001). Diabetes+HIIT, in comparison to the healthy control, had higher TGF-β levels (P=0.005). However, healthy+HIIT, compared to healthy control, had a lower expression of TGF-β (P=0.001). Finally, the healthy+HIIT groups, compared to the diabetes+HIIT group, had a lower TGF-β expression (P=0.001). Conclusion: Interval exercise could increase angiogenesis in diabetic samples through the increase of mir-126 and the reduction of TGF-β1 and EMAP-II.

The Metabolically Obese, Normal-Weight Phenotype in Young Rats Is Associated with Cognitive Impairment and Partially Preventable with Leptin Intake during Lactation.

The intake of high-fat diets (HFDs) and obesity are linked to cognitive impairment. Here, we aimed to investigate whether an early metabolically obese, normal-weight (MONW) phenotype, induced with an HFD in young rats, also leads to cognitive dysfunction and to evaluate the potential cognitive benefits of neonatal intake of leptin. To achieve this, Wistar rats orally received physiological doses of leptin or its vehicle during lactation, followed by 11 weeks of pair-feeding with an HFD or control diet post-weaning. Working memory was assessed using a T-maze, and gene expression in the hippocampus and peripheral blood mononuclear cells (PBMCs) was assessed with real-time RT-qPCR to identify cognition biomarkers. Young MONW-like rats showed hippocampal gene expression changes and decreased working memory. Animals receiving leptin during lactation presented similar gene expression changes but preserved working memory despite HFD intake, partly due to improved insulin sensitivity. Notably, PBMC Syn1 expression appears as an accessible biomarker of cognitive health, reflecting both the detrimental effect of HFD intake at early ages despite the absence of obesity and the positive effects of neonatal leptin treatment on cognition. Thus, the MONW phenotype developed at a young age is linked to cognitive dysfunction, which is reflected at the transcriptomic level in PBMCs. Neonatal leptin intake can partly counteract this impaired cognition resulting from early HFD consumption.

EFFECTS OF ACUTE AND CHRONIC CANNABIS/CANNABINOIDS ON COGNITIVE FUNCTION ACROSS THE LIFESPAN

Abstract Cannabis and cannabinoids such as THC (the major psychoactive component of cannabis) tend to impair cognitive performance, but almost all research on this topic has been conducted in young adults. Given that many aged individuals already exhibit cognitive deficits, it is important to determine how cannabis/cannabinoids affect cognition in this population. We used an animal model (young adult and aged rats) to evaluate the effects of both acute cannabis smoke and chronic oral THC on several tests of cognitive function. Both acute smoke (males only) and chronic THC (both sexes) enhanced working memory in aged rats, but neither affected young adults. In contrast, both regimens tended to impair performance on tests of spatial/episodic memory in an age-independent manner. Results suggest that although cannabis has potential for cognitive benefits in aging, its effects likely depend on both the cognitive domain tested and the manner in which it is administered.

DEVELOPMENT AND APPLICATION OF R1RHO DISPERSION IMAGING OF AGING MUSCLE IN AN ANIMAL MODEL

Abstract Compelling evidence from animal studies demonstrates that microvascular impairment contributes to the etiologies of several age-related chronic diseases, including sarcopenia. For example, capillary hemodynamic profiles are altered in old F344 rat spinotrapezius muscle compared with those of younger counterparts. However, a validated non-invasive measure of microvasculature geometry and structure has not yet been developed. Recently, it has been shown that R1ρ dispersion imaging at weak locking field frequencies (FSL) provides a unique way of characterizing microvessel size and density. Moreover, previous R1ρ images were acquired at strong FSL (≥500Hz) and used to measure the age-related differences linked to macromolecular deposition, such as collagen in the extracellular matrix. Here, we aimed to develop a non-invasive 3D volume R1ρ dispersion imaging method at weak FSLs (< 300Hz), to quantify microvasculature changes in skeletal muscle. We successfully implemented the protocol and applied it to the lower leg of five F334 female rats at age 15 mo. The whole lower leg of each rat was also imaged using conventional multislice T1-FLASH, Diffusion-weighted, and T2-MGE pulse sequences. We found that R1p value measured in calf muscles decreased from 46.92Hz to 41.63Hz by increasing FSL from 5Hz to 240Hz, which we suggest derives from the effects of rephasing some of the signal losses that arise from diffusion in intrinsic magnetic field gradients generated from microvessels. Future direction of this ongoing study will be to compare these results with data collected from young female rats at age 6 months and further validation using ex-vivo histology.

Transcranial Irradiation Mitigates Paradoxical Sleep Deprivation Effect in an Age-Dependent Manner: Role of BDNF and GLP-1

The growing prevalence of aged sleep-deprived nations is turning into a pandemic state. Acute sleep deprivation (SD) accompanies aging, changing the hippocampal cellular pattern, neurogenesis pathway expression, and aggravating cognitive deterioration. The present study investigated the ability of Near Infra Red (NIR) light laser to ameliorate cognitive impairment induced by SD in young and senile rats. Wistar rats ≤ 2 months (young) and ≥ 14 months (senile) were sleep-deprived for 72 h with or without transcranial administration of NIR laser of 830 nm. Our results showed that NIR photobiomodulation (PBM) attenuated cognitive deterioration made by SD in young, but not senile rats, while both sleep-deprived young and senile rats exhibited decreased anxiety (mania)-like behavior in response to PBM. NIR PBM had an inhibitory effect on AChE, enhanced the production of ACh, attenuated ROS, and regulated cell apoptosis factors such as Bax and Bcl-2. NIR increased mRNA expression of BDNF and GLP-1 in senile rats, thus facilitating neuronal survival and differentiation. The present findings also revealed that age exerts an additive factor to the cellular assaults produced by SD where hippocampal damages made in 2-month rats were less severe than those of the aged one. In conclusion, NIR PBM seems to promote cellular longevity of senile hippocampal cells by combating ROS, elevating neurotrophic factors, thus improving cognitive performance. The present findings provide NIR as a possible candidate for hippocampal neuronal insults accompanying aging and SD.

THE EFFECT OF CRONIC ISOLATED ADMINISTRATION OF CADMIUM CHLORIDE ON THE MORPHOLOGICAL STRUCTURES IN THE WALLS OF SMALL INTESTINE OF PREGNANT FEMALE RATS

In recent years, the anthropopolitical environmental polluntion with heavy metals has become one of the main threats to living organisms, including humans, and economic and technological progress is increasingly resulting in the disruption of natural ecosystems. Heavy metals include more than forty chemical elements of the periodic table, including chromium, cadmium, manganese, mercury, iron, cobalt, nickel, and others. They are often used in industry and are part of herbicides, insecticides, and medicines. In excessive quantities, they can change the structure of proteins, negatively affect metabolism, lead to cellular mutations, disrupt the structure and permeability of cell membranes, and cause malfunctioning of internal organs. Today, it is important to determine the impact of heavy metal compounds on the body in case of their constant (chronic) intake and accumulation in the body.
 The purpose of this study was to determine morphological changes in the structure of the walls in the small intestine of rats subjected to the chronic isolated exposure to cadmium salts in a dose of 2.0 mg/kg (enteral administration).
 The study involved 32 young female Wistar rats, with weights ranging from 180 to 300 g. Female rats with confirmed pregnancies were divided into the following groups: the first group served as the control, and the second group underwent isolated injection of cadmium chloride solution at a dose of 2.0 mg/kg.
 The results of the experimental daily intragastric long-term administration of cadmium chloride showed morphological changes in the structure of the small intestine in rats. The analysis of the data obtained showed that exposure to cadmium chloride in a dose of 2.0 mg/kg leads to a significant thinning of the villi of the small intestine and mucous membrane compared to the control. When exposed to cadmium chloride in the specified dose, the number of goblet cells in the mucous membrane of the small intestine villi increased at both periods of the study, which indicates an increase in the protective function of the small intestinal mucosa against the action of a negative factor. Under the influence of cadmium, the narrowing of the outer and inner diameters of the crypt was also determined that is confirmed by the calculation of the index of the diameter of the small intestine crypt.

Morphological and biochemical characteristics of osteogenesis during drug therapy of experimental osteoporosis

Relevance. Osteoporosis is a clinical and economic problem on a global scale. A significant contribution to solving the problem of effective treatment of osteoporosis can be the creation of drugs based on unique biologically active compounds.The aim of the study was the morphological substantiation of the experimental model of osteoporosis and a comprehensive (multifactorial) assessment of the effectiveness of its drug therapy.Materials and methods. The study was carried out on 40 mature female Wistar rats, which comprised 6 groups. A model of osteoporosis was formed in animals of four experimental groups (6 animals in each): the first and second groups (respectively) consisted of young rats, the third and fourth — old ones. Animals of the second and fourth groups were injected with a drug tested for its ability to activate the process of osteosynthesis. Rats of the fifth and sixth groups (young and old, 8 animals each), subjected to sham surgery, served as controls. As a result of the use of the histo-morphometric method and atomic absorption spectroscopy in the diaphysis of the femur, the thickness of the layers of the compact substance, the number of bone plates and osteocytes, as well as the amount of collagen, calcium and phosphorus were determined. Using enzyme immunoassay, bone remodeling markers — osteocalcin, sclerostin, osteoprotegerin, fibroblast growth factor-23 and nuclear factor kappa-β activator ligand (RANKL) — were determined in the blood serum. Statistical processing of the data was carried out using the GraphPad PRISM (USA) program to determine the median, upper and lower quartiles. Differences were considered significant at p < 0.01.Results. Modeling of osteoporosis induces atrophic thinning of the compact substance, a decrease in the number of osteocytes and bone plates in the diaphysis of the femur, a decrease in the content of collagen, calcium and phosphorus in them, a decrease in the concentration of osteocalcin, sclerostin, fibroblast growth factor, osteoprotegerin and an increase in the concentration of RANKL in the blood plasma, more pronounced in old animals. As a result of the use of the drug X3 for the treatment of osteoporosis, the following were revealed: a significant increase in the thickness of the compact substance, the number of osteocytes and bone plates in the diaphysis, the content of collagen, calcium and phosphorus in them, an increase in the concentration of biochemical markers of osteosynthesis, and a mild imbalance of RANKL. The increase in plasma levels of markers of bone remodeling was most pronounced when the drug X3 was combined with vitamin D3.Conclusion. 1. The used surgical-endocrine method of modeling osteoporosis leads to pronounced degenerative changes in osteocytes and their derivatives in all parts of the compact bone substance, and also causes significant disturbances in the mineral composition and an imbalance of bone remodeling markers, more pronounced in senile rats. 2. The tested drug X3, used for the treatment of osteoporosis, has a high degree of effectiveness, since it stimulates regenerative osteogenesis, restores the damaged structure of bone tissue elements, its organic and mineral components. 3. The restorative effect of the drug is more pronounced in senile rats.

Treadmill Exercise Reverses the Adverse Effects of Intermittent Fasting on Behavior and Cortical Spreading Depression in Young Rats.

Intermittent fasting (IF) and physical exercise (PE) have beneficial psychological and physiological effects, improving memory and anxiety-like behavior. However, the impact of this combination on brain electrophysiological patterns is unknown. We aimed to evaluate the behavior and parameters of a brain excitability-related phenomenon named cortical spreading depression (CSD) in young rats (31-87 days of life) submitted to IF and treadmill PE for eight weeks. Sixty-four male and female Wistar rats aged 24 days were randomized into control, IF, PE, and IF+PE groups. Behavioral tests (open field (OF), object recognition, and elevated plus maze (EPM)) were performed, and the CSD propagation features were recorded. IF caused behavioral responses indicative of anxiety (lower number of entries and time spent in the OF center and EPM open arms). IF also reduced the discrimination index for object recognition memory tests and increased the propagation velocity of CSD. PE rats displayed more entries into the OF center and lowered CSD propagation speed. Data suggest that IF worsens anxiety-like behavior and memory and accelerates CSD in young rats. In contrast, PE reverted the unfavorable effects of IF. The brain effects of IF and PE at younger ages are recommended for study.

Vortioxetine Reverses Impairment of Visuospatial Memory and Cognitive Flexibility Induced by Degarelix as a Model of Androgen Deprivation Therapy in Rats

Introduction: Androgen deprivation therapy (ADT) is a mainstay treatment for prostate cancer, but many patients experience cognitive impairment in domains mediated by the medial prefrontal cortex (mPFC) and hippocampus. Prostate cancer typically occurs in older patients (>65 years). As age is often accompanied by cognitive decline, it may impact the efficacy of any treatment aimed at restoring cognitive impairment induced by ADT. Vortioxetine, a multimodal antidepressant that improves cognition in depression, has been shown to be efficacious in elderly patients. Therefore, vortioxetine may improve cognition in older patients who experience cognitive decline after ADT. Methods: Young (3 months) and middle-aged (13 months) rats were used to investigate the influence of age on treating ADT-induced cognitive decline. As our previous studies used surgical castration, we tested if vortioxetine would reverse cognitive deficits associated with more translationally relevant chemical castration using degarelix. Vortioxetine was given in the diet for 21 days. Animals underwent behavioral testing to assess visuospatial memory mediated by the hippocampus and cognitive flexibility mediated by the mPFC. We also investigated changes in afferent-evoked responses in these regions in middle-aged rats. Results: Degarelix induced impairments in both visuospatial memory and cognitive flexibility that were reversed by vortioxetine. Vortioxetine also rescued afferent-evoked responses in the mPFC and hippocampus. However, modest age-related reductions in baseline visuospatial memory limited our ability to detect further decreases induced by degarelix in middle-aged rats due to a floor effect. Conclusion: These results suggest that vortioxetine may be a treatment option for older prostate cancer patients who experience cognitive decline after ADT.

Gut microbiota and metabolites in estrus cycle and their changes in a menopausal transition rat model with typical neuroendocrine aging.

Neuroendocrine alterations in the mid-life hypothalamus coupled with reproductive decline herald the initiation of menopausal transition. The certain feature and contribution of gut microflora and metabolites to neuroendocrine changes in the menopausal transition remain largely unknown. Fecal samples of rats experiencing different reproductive stages were collected and processed for 16S rRNA and liquid chromatography-mass spectrometry sequencing. The differences of gut microbiota and metabolites between young and middle-aged rats during proestrus and diestrus were analyzed, and their relationships to neuroendocrine aging were then examined. At the genus level, Anaeroyorax, Rikenella, Tyzzerella_3, and Atopostipes were abundant at proestrus, while Romboutsia, Turicibacter, Clostridium_sensu_stricto_1, Ruminococcaceae_NK4A214_group, CHKCI002, Ruminococcaceae_UCG-010, Staphylococcus, Family_XII_AD3011_group, Ruminococcaceae UCG-011, and Christensenellaceae_R_7_group were enriched in the diestrus of middle-aged rats. DNF00809, Phocea, and Lachnospiraceae_UCG-006 were found abundant during proestrus instead, while Bacteroides, Lactobacillus, Erysipelatoclostridium, Anaeroplasma, Anaerofustis, Parasutterella, and Enterococcus were enriched at the diestrus of young female individuals. Discriminatory metabolites were identified involving 90 metabolic pathways among the animal sets, which were enriched for steroid hormone biosynthesis, arachidonic metabolism, primary bile acid synthesis, and ovarian steroidogenesis. A total of 21 metabolites lacking in hormone-associated changes in middle-aged female individuals presented positive or negative correlations with the circulating luteinizing hormone, bile acid, fibroblast growth factor 19, and gut hormones. Moreover, close correlations were detected between the intestinal bacteria and their metabolites. This study documents specific gut microbial composition changes and concomitant shifting trends of metabolites during menopausal transition, which may initiate the gut-brain dysfunction in neuroendocrine aging.

Febrile seizures cause a decrease in calcium-permeable AMPA receptors at synapses of rat cortical and hippocampal pyramidal neurons

Febrile seizures (FS) are a prevalent childhood neurological disorder that can result in lasting functional alterations in neural networks, contributing to the onset of epilepsy and cognitive impairment [1]. Higher levels of calcium-permeable AMPA receptors (CP-AMPARs), which lack the GluA2 subunit, are detected in the hippocampus and cortex at an early age. CP-AMPARs are involved in various plastic changes within the central nervous system (CNS), including regular physiological processes (synaptic plasticity) and various pathological conditions. Such changes occur when these receptors are included in the neurons’ membrane, where they are not typically expressed. CP-AMPARs were demonstrated to incorporate into synapses during seizures [2]. The effect of FSs on CP-AMPAR expression is uncertain, and the resultant alterations in neuronal network function are unclear. The aim of this study was to determine whether the proportion of CP-AMPARs at synapses of pyramidal neurons in the rat entorhinal cortex and hippocampus alters immediately (at 15 min) and 48 h post FS. Ten-day-old rats were exposed to a stream of warm air (46 °C) for 30 minutes to induce hyperthermia, resulting in the development of FS. Only animals with FS that lasted for a minimum of 15 minutes were included in the study. The control group was comprised of littermates removed from the dam for an equivalent period but kept at room temperature. Isolated pyramidal neurons were used to determine the proportion of CP-AMPARs in the hippocampus. AMPAR-mediated currents were induced by application of 100 μM kainate. Excitatory postsynaptic currents (EPSCs) were evoked by extracellular stimulation in the entorhinal cortex. The antagonist IEM-1460 was used to selectively block CP-AMPARs. The rectification index of AMPA-mediated EPSCs was calculated to better assess the contribution of CP-AMPARs. Neurons expressing CP-AMPARs were visualized using the kainate-induced cobalt uptake method. Brain slices were stimulated with kainate while AR-5 and TTX were present. The DNQX blocker was used for the determination that the influx of Co2+ was mediated by AMPARs. Basal synaptic transmission was assessed by recording field postsynaptic responses in the hippocampus stimulated by Shaffer collaterals at different current strengths. FS induced a rapid decrease in the levels of CP-AMPARs on the membranes of pyramidal neurons in the hippocampus. As a result, 15 min after FS, IEM-1460 caused significantly less blockade of kainate-evoked current in neurons isolated from rat hippocampus compared to control (22% vs. 14%, p 0.05). A similar finding was observed for EPSCs evoked extracellularly in the entorhinal cortex, with a frequency of 10% in the FS group compared to 3% in the control group (p 0.05). Furthermore, the FS group’s neurons exhibited a significantly greater rectification index of EPSCs compared to the control group’s neurons. However, two days post-FS, no significant differences existed between the two groups. This observation may be attributed to the rapid decrease in the proportion of CP-AMPARs in pyramidal neurons at this stage. The cobalt uptake method supported electrophysiological findings, revealing higher staining levels in the CA1 field of the hippocampus and entorhinal cortex of control rats compared to FS rats. The observed effect surfaced 15 minutes after FS, and no divergences emerged between the groups after two days. Although the proportion of CP-AMPARs was reduced, basal neurotransmission levels in brain slices obtained from rats that underwent FS did not differ from control values. In summary, the expression of CP-AMPARs in entorhinal cortex and hippocampal pyramidal neurons in young rats decreases significantly with FS. These alterations do not impact the characteristics of basal synaptic transmission in the hippocampus.

A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity.

Age-related cognitive decline has been linked to distinct patterns of cellular dysfunction in the prelimbic cortex (PL) and the CA3 subregion of the hippocampus. Because higher cognitive functions require both structures, selectively targeting a neurobiological change in one region, at the expense of the other, is not likely to restore normal behavior in older animals. One change with age that both the PL and CA3 share, however, is a reduced ability to utilize glucose, which can produce aberrant neural activity patterns. The current study used a ketogenic diet (KD) intervention, which reduces the brain's reliance on glucose, and has been shown to improve cognition, as a metabolic treatment for restoring neural ensemble dynamics in aged rats. Expression of the immediate-early genes Arc and Homer1a were used to quantify the neural ensembles that were active in the home cage prior to behavior, during a working memory/biconditional association task, and a continuous spatial alternation task. Aged rats on the control diet had increased activity in CA3 and less ensemble overlap in PL between different task conditions than did the young animals. In the PL, the KD was associated with increased activation of neurons in the superficial cortical layers, establishing a clear link between dietary macronutrient content and frontal cortical activity. The KD did not lead to any significant changes in CA3 activity. These observations suggest that the availability of ketone bodies may permit the engagement of compensatory mechanisms in the frontal cortices that produce better cognitive outcomes.

Impact of continuous testosterone exposure on reproductive physiology, activity, and pain-related behavior in young adult female rats

Testosterone may reduce pain in cisgender women and transgender men. Rodents can provide a useful model for investigating physiological effects of hormone therapy. To this end, continuous-release testosterone or blank (placebo) capsules were implanted s.c. into young adult female rats, and three weeks later rats were either ovariectomized or sham-ovariectomized. Testosterone treatment that mimicked previously reported endogenous levels in males eliminated estrous cycling and decreased uterine weight. Testosterone also significantly increased body weight and suppressed the increases in daily wheel running observed in placebo controls over time. Subsequent ovariectomy or sham-ovariectomy decreased wheel running in all groups, but testosterone-treated rats recovered significantly more quickly than did placebo-treated rats. Neither testosterone nor ovariectomy significantly altered hindpaw mechanical threshold. Two weeks after sham/ovariectomy surgery, injection of Complete Freund Adjuvant (CFA) into one hindpaw reduced wheel running and mechanical threshold in all groups; running significantly decreased from the first to second day after CFA in testosterone- but not in placebo-treated rats. Morphine 1.0 but not 3.2 mg/kg increased CFA-suppressed wheel running similarly in all groups, whereas both doses of morphine increased CFA-suppressed mechanical threshold. These data suggest that weeks-long testosterone treatment with or without ovariectomy may provide a useful physiological model of testosterone therapy as used in human gender transition. Although testosterone administered at levels similar to those in gonadally intact males tended to hasten female rats' recovery from surgery, it did not decrease maximal pain-related behaviors after surgery or hindpaw inflammatory insult, nor did it alter opioid antinociception.

Object-place-context learning impairment correlates with spatial learning impairment in aged Long-Evans rats.

The hippocampal formation is vulnerable to the process of normal aging. In humans, the extent of this age-related deterioration varies among individuals. Long-Evans rats replicate these individual differences as they age, and therefore they serve as a valuable model system to study aging in the absence of neurodegenerative diseases. In the Morris water maze, aged memory-unimpaired (AU) rats navigate to remembered goal locations as effectively as young rats and demonstrate minimal alterations in physiological markers of synaptic plasticity, whereas aged memory-impaired (AI) rats show impairments in both spatial navigation skills and cellular and molecular markers of plasticity. The present study investigates whether another cognitive domain is affected similarly to navigation in aged Long-Evans rats. We tested the ability of young, AU, and AI animals to recognize novel object-place-context (OPC) configurations and found that performance on the novel OPC recognition paradigm was significantly correlated with performance on the Morris water maze. In the first OPC test, young and AU rats, but not AI rats, successfully recognized and preferentially explored objects in novel OPC configurations. In a second test with new OPC configurations, all age groups showed similar OPC associative recognition memory. The results demonstrated similarities in the behavioral expression of associative, episodic-like memory between young and AU rats and revealed age-related, individual differences in functional decline in both navigation and episodic-like memory abilities.

Putative effect of chronic renal failure on granular convoluted tubule of submandibular gland in male rats: Immunohistochemical and ultrastructural study

ObjectiveThis study aimed to investigate the ultrastructural and immunohistochemical changes in the granular convoluted tubule (GCT) of rodents' submandibular gland (SMG) upon theinduction of chronic renal failure. Material and methodsThirty young adult Sprague-Dawley rats were randomized into three groups: the Control group, rats received no intervention; the Sham group, rats underwent surgical incision without nephrectomy; the Experimental group, rats underwent surgical procedures to induce chronic renal failure. Afterward, SMG was examined for histological and ultrastructural changes and immunohistochemical staining for Renin. ResultsHistologically, the experimental group demonstrated cytoplasmic vacuolization within the seromucous acini and ducts. Several GCTs were proliferating, whereas others exhibited degenerative changes in the form of disturbed cytoplasmic architecture. On the ultrastructural level, both acini and ductal segments showed degenerative changes Interestingly, immunohistochemical examination of the lining cells of GCT and intralobular ducts of the experimental group revealed the presence of Renin. ConclusionRenal failure induced histological, immunohistochemical, and ultrastructural variations within GCTs of SMG.

Specific inhibitor of Wnt/beta-catenin pathway can alter behavioral responses in young rats with malformed cortices

The Wnt/beta-catenin pathway plays a crucial role in regulating cellular processes and has been implicated in neural activity-dependent learning as well as anxiety. However, the role of this pathway in young children with abnormal cortical development is unknown. Cortical malformations at early development, behavioral abnormalities, and a susceptibility to seizures have been reported in rats prenatally exposed to methylazoxymethanol. In this study, we aimed to investigate whether we could improve the behavioral deficits in young rats with malformed cerebral cortices by modulation of the Wnt/beta-catenin pathway. We found a small molecule Wnt/beta-catenin inhibitor (CWP) that increased exploratory behavior in the open field test (P9, CWP 100 ug treatment, peripheral exploration, P = 0.011) and social behavior test (P12, CWP 250 ug treatment, distance traveled in center, P = 0.033) and decreased anxiety in fear conditioning. However, it did not reduce the susceptibility to seizures. After high dose (250 ug) CWP treatment at P12, phosphocreatine and glutathione (GSH) were decreased in the cortex at P15 (P = 0.021). These findings suggest that the role of Wnt/beta-catenin signaling in exploratory behavior and anxiety during early development warrants further investigation.

Effects of Acetaminophen on the Reproductive Parameters and the Ameliorative Effects of Rutin and Mesenchymal Stem Cells in Male Rats

The present study has been designed to evaluate the effects of acetaminophen on the reproductive parameters and the ameliorative effects of rutin and Mesenchymal stem cells in male rats. The rats were divided into two studies: firstly, twenty young male rats were used as a source of bone marrow-derived MSCs. Secondly, fifty adult male rats were divided into 5 groups: Control group (G1); rats were administrated of AAP (750 mg/kg b.w.) every 72h for 21 days, then left for 30 and 60 days without treatment (G2), rats were administrated of AAP for 21 days then treated with RT (25mg/kg b.w/d) for 30 and 60 days (G3), rats were administrated of AAP for 21 days then the rats were injected by BM-MSCs (1.5x 106 cells in 0.5 PBS) in the tail vein for 30 and 60 days (G4), and rats were administrated of AAP for 21 days then the rats were injected by BM-MSCs in the tail vein, then treated with RT for 30 and 60 days (G5). Administration of AAP produced a significant decrease in the mean value of the Te, LH, and FSH levels after 30 and 60 days as compared to the C groups. Whereas rats treated with RT and MSCs showed a significantly high increase in the mean values of these hormone levels after 30 and 60 days compared with the AAP group. In conclusion, this study demonstrated that RT and MSCs when treated in combination, are protected against the AAP-induced decrease in the hormone level of testicular.

Challenges in reproducing the standard lithium Pilocarpine model of temporal lobe epilepsy in wistar rats: troubleshooting strategies

Introduction: Animal model of temporal lobe epilepsy (TLE) provide an essential platform to study the disease pathophysiology, and disease modifying management protocols. Lithium –pilocarpine model is one of the most favored model. Many practical difficulties have been encountered while creating this model in this study as well as by other authors. We have systematically attempted to compile all issues and their possible solutions in establishment of Li-Pi model of status epilepticus in wistar rats, to provide a dependable protocol with improved seizure induction rates and lower mortality rates. Materials and Methods: Young small size male wistar rats (100-150gm) were injected with lithium chloride (LiCl) (127 mg/kg, i.p.), followed by methyl scopolamine (1mg/kg, i.p.) after 18-22 hrs. Precisely after 30 minutes, dose of pilocarpine (i.p.) was administered. Post seizures, diazepam (10 mg/kg) was injected to reduce seizures severity and to increase survival rate and rats were fed glucose (10% of body weight) through oral gavage. Model creation was validated by histological examination of hippocampus. The rats which did not develop seizures, were reutilized for the model generation after drug wash-out period of 48 hours. Results: Initial model creation was unsuccessfully attempted in 75 rats. Standard described protocol of three incremental doses of pilocarpine (10mg/kg, maximum of 30mg/kg) did not elicit epilepsy. Loading dose of 30mg/kg pilocarpine caused stage 1 epilepsy in 60% rats; second dose of pilocarpine (30mg/kg), caused stage 2 epilepsy in 70% rats. Successful TLE model creation was seen in 33 out of 57 rats, using proposed modification in which 2 incremental doses of pilocarpine (30mg/kg each) were followed by 3 doses of 10mg/kg each; 6 rats died. Conclusions: The study provides a detailed procedure for lithium pilocarpine model creation and various pitfalls encountered. Modified pilocarpine dosage led to improved seizure induction rates (58%) and lower mortality rates (10%). Keywords: Epilepsy animal model; Status epilepticus; lithium-pilocarpine; Animal mortality

Comparison of physiological and biochemical changes in old and young hyperglycemic rats submitted to aerobic exercise and anabolic steroid use

Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity. Testosterone is known to cause muscle hypertrophy, reduced fat mass, and increased body strength. The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia. We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young, treated non-diabetic young, untreated diabetic young, and treated diabetic young rats, and 32 aged Wistar rats to groups of untreated non-diabetic elderly, treated non-diabetic elderly, untreated diabetic elderly, and treated diabetic elderly rats, with eight animals each group. The treated non-diabetic and treated diabetic groups received injections of 15 ​mg/kg weight Durateston™. All the trained groups performed aquatic training with an overload of 5% of the body mass. Following the experiment, we anesthetized and euthanized the animals after exercise (exhaustion). Hemoglobin, erythrocytes, and hematocrit values were higher in the treated groups. The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups (p ​< ​0.05). As for the lipid profile, untreated rats had the highest values. Glucose concentration was higher at rest and after exercise in the untreated diabetic groups (p ​< ​0.05). Lactate was more elevated in the untreated diabetic groups, and the testosterone-treated groups performed the longest swimming time after the maximal test (p ​< ​0.05). The use of testosterone in conjunction with physical exercise improved physical performance in water, blood glucose, and lipid profiles.

Muscimol inactivation of dorsal striatum in young and aged male rats does not affect paired associates learning performance.

Improving cognitive health for older adults requires understanding the neurobiology of age-related cognitive decline and the mechanisms underlying preserved cognition in old age. During spatial learning tasks, aged humans and rodents shift navigation preferences in favor of a stimulus-response learning strategy. This has been hypothesized to result from competitive interactions of the caudate nucleus/dorsal striatum (DS) memory system with the hippocampus (HPC)-dependent spatial/allocentric memory system. In support of this hypothesis, a recent study reported that inactivation of the DS in aged rodents rescued HPC-dependent spatial learning on a T-maze (Gardner, Gold, & Korol, 2020). Currently, it is unclear whether a shift from HPC-dependent to DS-dependent behavior also contributes to age-related cognitive decline outside of spatial learning and memory. To test the hypothesis that inactivation of the DS can restore age-related cognitive function outside of spatial behavior, the present study bilaterally inactivated the DS of young (n = 8) and aged (n = 7) rats during visuospatial paired associates learning (PAL). This study found that inactivation of the DS did not alter PAL performance in young or aged rats, but did alter a positive control, DS-dependent spatial navigation task. This observation suggests that elevated DS activity does not play a role in the decline of HPC-dependent PAL performance in aged male rats. Given the persistent tendencies of aged rodents toward DS-dependent learning, it will be worthwhile to explore further the coordination dynamics between the HPC and DS that may contribute to age-related cognitive decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).