Young Rats Research Articles

Dietary soy protein reverses obesity-induced liver steatosis and alters fecal microbial composition independent of isoflavone level

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern that is exacerbated by the obesity pandemic. Dietary interventions have the potential to alleviate obesity-associated MASLD through variable mechanisms, including optimizing the gut microbiota. Previously, we reported that soy protein concentrate (SPC) with low or high levels of isoflavone (LIF or HIF) protected young obese Zucker rats from developing liver steatosis. The current study was designed to test whether SPC-LIF and SPC-HIF diets would reverse liver steatosis and alter fecal microbial composition in adult obese Zucker rats with existing steatosis.MethodsSix-week-old male obese Zucker rats (n = 26) were fed a casein control diet (CAS) for 8 weeks and 7 rats were randomly selected and sacrificed to confirm liver steatosis. The remaining rats were randomly assigned to receive CAS, SPC-LIF, or SPC-HIF diet (n = 6–7/group) for an additional 10 weeks.ResultsCompared to CAS diet, feeding SPC-LIF and SPC-HIF diets resulted in significantly lower liver weight, liver steatosis score, and liver microvesicular score (p < 0.05), but did not lead to difference in body weight, liver macrovesicular score, serum ALT, or serum AST. Isoflavone levels (e.g., LIF vs. HIF) did not affect any of these measurements except in the SPC-HIF group, which had an additional decrease in liver weight (p < 0.05) compared to the SPC-LIF group. The SPC-HIF group also had significantly higher levels of the aglycone forms of daidzein, genistein, and equol as well as the total levels of daidzein, genistein, and equol compared to SPC-LIF or CAS diet fed rats (p < 0.05). The distribution of microbial communities based on measures of beta diversity of both SPC-LIF and SPC-HIF groups were significantly different to that of the CAS group (p ≤ 0.005). Alpha-diversity did not differ between any of the groups.ConclusionTaken together, dietary soy protein can reverse liver steatosis in adult Zucker rats, and the reversal of steatosis is accompanied by alterations in gut microbial composition.

Tooth eruption status and bite force determine dental microwear texture gradients in albino rats (Rattus norvegicus forma domestica).

Dental microwear texture analysis (DMTA) is widely applied for inferring diet in vertebrates. Besides diet and ingesta properties, factors like wear stage and bite force may affect microwear formation, potentially leading to tooth position-specific microwear patterns. We investigated DMTA consistency along the upper cheek tooth row in young adult female rats at different growth stages, but with erupted adult dentitions. Bite forces for each molar (M) position were determined using muscle cross-sectional areas and lever arm mechanics. Rats were categorized into three size classes based on increasing skull length. Maximum bite force increased with size, while across all size classes, M3 bite force was almost 1.4 times higher than M1 bite force. In size class 1, M1 and M2 showed higher values than M3 for DMTA complexity, height, and volume parameters, while in size class 3, M1 had the lowest values. Comparing the same tooth position between size classes revealed opposing trends: M1 and M2 showed, for most parameters, decreasing roughness and complexity from size class 1-3, while M3 displayed the opposite trend, with size class 1 showing lowest, and either size class 2 or 3 the highest roughness and complexity values. This suggests that as rats age and M3 fully occludes, it becomes more utilized during mastication. DMTA, being a short-term diet proxy, is influenced by eruption and occlusion status changes. Our findings emphasize the importance of bite force and ontogenetic stage when interpreting microwear patterns and advise to select teeth in full occlusion for diet reconstruction.

Protective effects of electroacupuncture on senile osteoporosis in rats.

The objectives were to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in aged rats and investigate the underlying mechanisms. This study included aged (24-month-old; n = 16) and young (3-month-old; n = 8) male Sprague-Dawley rats. Aged rats were further randomized 1:1 to an aged control group (Aged; n = 8) and an EA treatment group (EA; n = 8). The 3-month-old rats served as young controls (Young). EA rats received EA at ST36, SP6, GB34 and SP10 bilaterally for 30 min a day, 5 days a week, for 8 weeks. EA significantly increased serum markers of bone formation in Aged rats. There were no significant differences in serum markers of bone resorption between EA and Aged rats. Deterioration of bone mineral density (BMD) and trabecular bone architecture was observed in the Aged group, while EA significantly increased BMD of the left femur and L5 vertebral body in aged rats. Aging-induced deterioration of trabecular bone architecture was partially reversed in EA rats. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells in EA compared with Aged groups. The mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells in EA compared with Aged groups. EA may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. EA may represent a therapeutic option for senile osteoporosis.

Differential effects of chronic and intermittent administration of taurine on alcohol binge drinking in male rats

Episodic consumption of high doses of alcohol in a short period (binge drinking - BD) among adolescents is known to be harmful to their brain development. Chronic use of taurine increases voluntary alcohol consumption and shows an anxiolytic-like effect in rats. In this study, we evaluated the differential effects of chronic and intermittent taurine administration on alcohol consumption and behavioral changes in adolescent and young adult rats subjected to the BD model. Male Wistar rats (35 days old) were divided into 4 groups for daily intraperitoneal administration of saline (SAL); taurine, 100 mg/kg (TAU); taurine on BD days and saline on intervals (TAU/SAL); and saline on BD days and taurine on intervals (SAL/TAU). They were exposed to 4 cycles of BD, with free access to alcoholic solution (20 % w/v), for 2 h, 3 days per week. At the end of the 3rd cycle, anxiety-like behaviors were assessed using the light-dark task. After euthanasia, plasma and prefrontal cortex samples were collected to measure corticosterone and BDNF levels, respectively. Chronic taurine treatment did not alter alcohol consumption in rats, whereas intermittent administration increased alcohol intake after 4 BD exposures (TAU/SAL: +19.4 % and SAL/TAU: +21.6 %). No anxiolytic-like effects were found by taurine administration, nor were there changes in serum corticosterone or BDNF levels in the frontal cortex of young adult rats. Intermittent taurine, but not chronic treatment, increased alcohol intake among rats after the second week of exposure. The translation of these results to humans is concerning since the combination of alcohol and drinks containing taurine is common among adolescent and young adult individuals.

Late-onset caloric restriction improves cognitive performance and restores circadian patterns of neurotrophic, clock and epigenetic factors in the hippocampus of male old rats.

Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.

Spermidine protects cellular redox status and ionic homeostasis in D-galactose induced senescence and natural aging rat models.

Impaired redox homeostasis is an important hallmark of aging. Among various anti-aging interventions, caloric restriction mimetics (CRMs) are the most effective inpromoting health and longevity. The potential role of spermidine (SPD) as a CRM in modulating oxidative stress and redox homeostasis during aging remains unclear. Thisstudy aimed to investigate the protective effect of SPD inD-galactose (D-gal) accelerated induced senescence model and naturally aged rats. Young male rats (4months), D-gal induced (500 mg/kg b. w., subcutaneously) aging model and naturally aged (22months) rats were supplemented with SPD (10 mg/kg b. w., orally) for 6weeks. The results showed that SPD supplementation suppresses the age induced increase in reactive oxygen species, lipid peroxidation andprotein oxidation. Additionally, it increases the level ofantioxidants, plasma membrane redox system in erythrocytes and membrane. These results also indicate that membrane transporter activity is correlated with the susceptibility of the erythrocyte towards oxidative damage. We therefore present evidence that SPD improves redox status and membrane impairments in erythrocytes in experimental and naturally aging rat models, however, more research is required to recommend a potential therapeutic role for SPD as an anti-aging intervention strategy.

A comparative study of the established methods and evaluation of rat trauma models.

Scientific animal models are indispensable for studying trauma repair. This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma numbers, locations, and trauma attachment tension unloaders and rat age. A four-trauma self-upper, lower, left and right control model; a two-trauma self-trauma bare and ring control model; and a young and old rat trauma model were created to evaluate the condition of these traumas. In the four-trauma self-control model, the healing status of the upper proximal cephalic trauma was better than that of the lower proximal caudal trauma, whereas there was no significant difference between the left and right trauma. The healing rate and postwound condition of the trauma with a ring control in the two-trauma model were better than those of the bare side. The healing speed of the old rats was slower, and the amount of extracellular matrix in the subcutaneous tissue after healing was significantly lower than that of the young rats. The double trauma with a ring is a more scientific and reasonable experimental model. There is a significant difference between young and old rats in the wound healing process. Therefore, the appropriate age of the rats should be selected according to the main age range of the patients with similar conditions in the clinical setting being mimicked.

Sex differences and testosterone interfere with the structure of the gut microbiota through the bile acid signaling pathway

BackgroundThe gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.Methods16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.ResultsThe composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.ConclusionSex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.

Aging by autodigestion.

The mechanism that triggers the progressive dysregulation of cell functions, inflammation, and breakdown of tissues during aging is currently unknown. We propose here a previously unknown mechanism due to tissue autodigestion by the digestive enzymes. After synthesis in the pancreas, these powerful enzymes are activated and transported inside the lumen of the small intestine to which they are compartmentalized by the mucin/epithelial barrier. We hypothesize that this barrier leaks active digestive enzymes (e.g. during meals) and leads to their accumulation in tissues outside the gastrointestinal tract. Using immune-histochemistry we provide evidence in young (4 months) and old (24 months) rats for significant accumulation of pancreatic trypsin, elastase, lipase, and amylase in peripheral organs, including liver, lung, heart, kidney, brain, and skin. The mucin layer density on the small intestine barrier is attenuated in the old and trypsin leaks across the tip region of intestinal villi with depleted mucin. The accumulation of digestive enzymes is accompanied in the same tissues of the old by damage to collagen, as detected with collagen fragment hybridizing peptides. We provide evidence that the hyperglycemia in the old is accompanied by proteolytic cleavage of the extracellular domain of the insulin receptor. Blockade of pancreatic trypsin in the old by a two-week oral treatment with a serine protease inhibitor (tranexamic acid) serves to significantly reduce trypsin accumulation in organs outside the intestine, collagen damage, as well as hyperglycemia and insulin receptor cleavage. These results support the hypothesis that the breakdown of tissues in aging is due to autodigestion and a side-effect of the fundamental requirement for digestion.

Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218

Abstract Young children are attracted to flavored foods with enhancers, particularly monosodium glutamate (MSG). Experimental studies have proven that MSG can alter the hypothalamic–pituitary–adrenal (HPA) axis response in neonates. We, therefore, investigated the modulation of microRNAs (miRNAs) by dietary MSG and its association with the stimulation of the HPA axis and inflammatory response in young male rats. One-month-old male rats were fed chow enriched with MSG (3 g/kg) for 16 weeks. Feeding MSG to rats markedly up-regulated hypothalamic miR-218, Toll-like receptors-4, and nuclear factor-kB but down-regulated miR-155 and glucocorticoid receptors (GR). In addition, it triggered a remarkable elevation in adrenocortical lipid peroxidation and depletion of antioxidants. These changes were coupled with increased plasma levels of the HPA axis hormones, comprising corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone levels, and serum pro-inflammatory cytokines. Taken together, current findings indicated that MSG caused an activation of the HPA axis, a down-regulation of GRs, and a systemic inflammatory response. These disturbances were associated with modulating hypothalamic miRNAs, encompassing miR-218 and 155.

Investigating tributyltin's toxic effects: Intestinal barrier and neuroenteric disruption in rat’s jejunum

The expansion of economic activities in coastal areas has significantly increased chemical contamination, leading to major environmental challenges. Contaminants enter the human body through the food chain, particularly via seafood and water consumption, triggering biomagnification and bioaccumulation processes. The gastrointestinal tract (GIT) acts as a selective barrier, protecting against chemical pollutants and maintaining homeostasis through a complex network of cells and immune responses. This study assessed impact of tributyltin (TBT), a highly toxic organometallic compound used in antifouling coatings for ships, on the GIT and myenteric neural plasticity in young rats. TBT exposure leads to histopathological changes, including epithelial detachment and inflammatory foci, especially at lower environmental doses. The study found that TBT causes significant reductions in villi height, increases in goblet cells and intraepithelial lymphocytes, and disrupts the myenteric plexus, with higher densities of extraganglionic neurons in exposed animals.

Slight and hidden hearing loss in young rats is associated with impaired recognition memory and reduced myelination in the corpus callosum.

Slight and hidden hearing loss in children have been linked to cognitive and social difficulties, and yet the neurobiological mechanisms behind these issues remain poorly understood. Most animal models focus on severe hearing loss, leaving the effects of hidden or slight hearing loss largely unexplored. To uncover the neural mechanisms connecting slight/hidden hearing loss to cognitive and social challenges, we induced hearing loss in young (4-week-old) Wistar rats through noise exposure. We then examined cognitive function (object recognition test) and social behavior (juvenile play behavior and social interaction). Changes in brain anatomy were assessed using cortical thickness and hippocampal size measurements, while (immuno)histochemical staining investigated neuronal circuitry maturation (myelin basic protein, parvalbumin, and perineuronal nets) and neurogenesis (doublecortin). Noise-exposed rats displayed slight high-frequency hearing loss (around 20 dB) and hidden hearing loss at other tested frequencies. This slight/hidden hearing loss was associated with impaired object recognition but did not alter social behavior. Slight/hidden hearing loss was associated with reduced myelin basic protein expression in the corpus callosum but no other alterations in cortical thickness, hippocampal size, or other markers of maturation and neurogenesis were found. These findings show that even slight/hidden hearing loss can lead to subtle brain alterations tied to cognitive deficits. This study emphasizes the need for further research to fully understand the brain changes associated with slight/hidden hearing loss and to pinpoint the mechanisms connecting these changes to behavioral deficits. This information is crucial to develop interventions to prevent the cognitive and social consequences of hearing loss. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Therapeutic effect of bloodletting on bone deterioration induced by hypobaric hypoxia in young rats

ObjectivesHigh-altitude regions, comprising hypoxic conditions, are associated with different altitude-induced pathologies, including a reduction in bone density. Elucidating the mechanisms underlying bone degradation in such environments and developing targeted interventions and therapeutics is important. Bloodletting therapy has promising clinical applications, but its effects on the skeletal system and bone homeostasis are not well understood. The aim of this study was to investigate the effects of a hypobaric hypoxia environment on specific femoral morphological and structural properties, including bone volume, cortical thickness, and trabecular microarchitecture, in juvenile Sprague–Dawley (SD) rats, and to explore the potential modulating effects of a bloodletting intervention on these parameters. MethodsMale SD rats, 6 weeks of age, were subjected to a simulated hypobaric hypoxia environment, replicating a 5000-m altitude, for 12 weeks. For the bloodletting intervention group, rats were subjected to a weekly 500 μL tail vein blood withdrawal. Micro-CT technology, hematoxylin and eosin staining, and tartrate-resistant acid phosphatase staining were employed to comprehensively assess the femoral microstructure, tissue architecture, and cellular morphology. Additionally, immunofluorescence analysis was conducted to quantify the expression of key proteins, and transcriptome analysis was performed to identify differentially expressed genes. ResultsExposure of rats to hypobaric hypoxia led to a significant reduction in bone mineral content, trabecular bone number, and cortical bone thickness, suggesting a deterioration of bone microstructure. Additionally, the hypoxic environment upregulated the expression of RANKL and HIF-1α, while downregulating RUNX2. Notably, although bloodletting intervention did not significantly reverse these bone structural changes, transcriptome analysis revealed its regulatory influence on the expression of key genes, particularly Mmp2, Fosl2, and URS0000B2A65A, which are implicated in pathways governing the hypoxic response, osteoclast differentiation, and PI3K–Akt signaling. ConclusionThis study highlights the detrimental effect of hypobaric hypoxia on the bone microstructure of juvenile rats and underscores the therapeutic potential of bloodletting to ameliorate this condition. Additionally, our study on the regulatory mechanisms mediating bloodletting's effects on gene expression offers fresh perspectives on bone alterations. It suggests promising avenues for the development of novel preventative measures and targeted therapies to address the challenges posed by related bone disorders.

Chromium Selectively Accumulates in the Rat Hippocampus after 90 Days of Exposure to Cr(VI) in Drinking Water and Induces Age- and Sex-Dependent Metal Dyshomeostasis.

Hexavalent chromium (Cr[VI]) is a widespread environmental pollutant in air and water that is primarily attributed to industrial pollution. The current maximum contaminant levels (MCLs) for drinking water from the World Health Organization and the U.S. Environmental Protection Agency (0.05 and 0.1 mg/L, respectively) were set based on contact dermatitis and warrant further toxicological investigation. While Cr(VI) is neurotoxic and accumulates in the brain, most animal studies only report whole-brain Cr, leaving large knowledge gaps. Few studies consider differences between ages or sexes, and fewer consider essential metal dyshomeostasis. We sought to investigate where Cr accumulates in the brain, considering sex and age differences, following a 90-day drinking water exposure to current MCLs. Here, we report Cr levels in six brain regions of rats exposed to drinking water Cr(VI). We observed Cr only accumulated in the hippocampus, and only in older females. We further assessed changes to essential metals in the hippocampus, observing opposite effects across sexes and between young rats compared to older rats. In sum, our data indicate drinking water Cr(VI) selectively targeted the hippocampus, with geriatric females accumulating the most Cr, and induced significant essential metal dyshomeostasis even in tissues lacking evident Cr accumulation.

Detrimental effect of prenatal progesterone exposure on anxiety and depressive-like responses in adult male and female rat offspring: role of plasma, hippocampal corticosterone and hippocampal progesterone receptors

In clinical practice, the use of exogenous progesterone (Pro) is often required in assisted reproduction programs due to reduced levels of the hormone and the risk of miscarriage. Exposure to the hormone reduces anxiety in rodents, but the long-term effects of prenatal exposure in adult offspring are unknown. Therefore, the present study was designed to investigate the effect of prenatal Pro treatment on anxiety- and depression-like behavior and the effect on plasma, hippocampal corticosterone (CORT) and hippocampal progesterone receptor (PR) in young adult male and female rat offspring. The behavioral responses of offspring of both sexes were tested in the open field, and the elevated plus maze tests, and for depressive-like behavior in the sucrose preference test, the forced swimming test and the splash test. CORT levels and PR expression were measured by ELISA. The results indicate that prenatal Pro exposure at low and high doses (10 and 50 mg/kg, s.c. during G0-G10) induces anxiogenic and depressive-like effects compared to vehicle-treated controls, which are associated with high plasma and hippocampal CORT levels and upregulated hippocampal PR in male and female adult offspring. Our results demonstrate that prenatal Pro exposure has detrimental effects on the emotional status of male and female adult offspring, which may be associated with long-term changes in hormonal homeostasis.

Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Exploring the genetic expression of Sdf1, Foxc1 and histologic changes following mandibular advancement and recovery phase in Wistar rats.

PurposeThis study evaluated the impact of mandibular advancement on Sdf1 and Foxc1 gene expression in the mandibular condylar cartilage of young Wistar rats. By examining the changes that occur during a unique one-month recovery period, it highlights the critical role of gene expression and condylar adaptation during the recovery phase. The analysis focused on whether, during the recovery period, reversal changes occur when functional appliances are removed and whether genetic expression important for condyle growth and adaptation downregulates. Material and MethodsThe study involved 30 male Wistar rats divided into 2 control groups Appliance Control and Recovery Control groups, and 2 experimental groups, the Appliance group with mandibular advancement bite-jumping appliance for 30 days, and the Recovery group with appliance for 30 days followed by a 30-day recovery. Molecular analysis of condylar cartilage using real-time RT-PCR and histological assessments was conducted. ResultsSignificant genetic expression alterations were noted in both the experimental groups for Sdf1 (p < 0.05) and Foxc1 (p < 0.05). According to histological investigations, significant alterations with an increase in the proliferative and hypertrophic layer in condylar cartilage were seen. ConclusionMandibular advancement bite-jumping appliances induce proliferative and hypertrophic layer changes in mandibular condylar cartilage, shown by elevated Foxc1 levels and decreased Sdf1 levels. Post-appliance removal, persistent gene expression reveals a true joint stimulation.

Long-term liver deportalisation in stable and time prolonged prehepatic portal hypertension model affects expression of hypoxia, angiogenesis, apoptosis, and autophagy markers in the young rats’ liver

prehepatic portal hypertension in children cause severe and life-threatening complications, that highlights the need in in-depth investigations of pathogenetic mechanisms, which contribute to prehepatic portal hypertension-associated liver pathology. In developed stable experimental prehepatic portal hypertension model in adolescent rat males we aimed to assess the expression levels of the key molecular markers of hypoxia, angiogenesis, autophagy, and apoptosis in the liver tissue after 6-month deportalization. Partial portal vein ligation was performed in 4-week old male rats. After 6-months tissue samples from PHP-model, sham operated and control animals were studied by western blot to identify protein levels of markers related to prehepatic portal hypertension -induced liver injury. Partial portal vein occlusion upregulated hypoxia inducible factor -1α (by 4.67 folds vs. control, p&lt;0.001) and vascular endothelial growth factor protein expression levels (by 2.33 folds vs. control, p&lt;0.001) suggesting chronic hypoxia development. Abnormally high levels of angiostatin isoforms were found (by 9.88 folds vs. control, p&lt;0.001) to signify angiogenesis dysregulation. Significant caspase-3 (23.4-fold increase vs. control, p&lt;0.001) overexpression is executive phase of apoptotic cell death evidence. Dramatic LC3 level expression indicates existence of crosstalk between autophagy and apoptosis that contribute to fibrotic changes. Hypoxia-induced events, impaired angiogenesis regulation, enhanced autophagy and apoptosis are contributing factors of prehepatic portal hypertension -induced liver injury. A better understanding of subtle molecular mechanisms of this pathology may pave the way for innovative treatment options.

High iron in mouse olfactory ensheathing cells at the glia limitans in the olfactory bulb underlies MRI T2* hypointensity

Abstract Brain iron is important for normal function, and aberrantly high iron is often associated with neuroinflammation and neurodegeneration. Oligodendrocytes are a major source of iron in brain as are iron-laden activated macrophages and microglia. T2*-weighted MRI detected a large decrease in signal at the olfactory nerve layer (ONL) in normal young mice over the period of 3 to 12 weeks of age, consistent with iron accumulation in this region. This signal change was most prominent in the inner nerve fiber layer (iNFL). Iron histochemistry, ferritin immunohistology, and electron microscopy showed that there was high iron and ferritin in the olfactory ensheathing cells (OECs) in the iNFL of ONL. The iron concentration in the iNFL was calculated to be approximately 2–3 mM based on MRI T2* relaxivity. The glomerular region near the high-iron iNFL had evidence of neuroinflammation markers of activated microglia and lipofuscin. Lipofuscin was found within the activated microglia as early as 6 weeks. In rats, MRI T2* signal loss in the ONL and high iron levels and lipofuscin were only detected in older rats (11 months) but not in young rats. These results indicate that mouse OECs develop high levels of iron at an early age. It is not clear if this iron is important for mouse OEC function or a result of phagocytic activity of OECs. The relation between iron and inflammation may be interesting to study in these young, healthy mice.

Sex-dependent effects of acute stress and alcohol exposure during adolescence on mRNA expression of brain signaling systems involved in reward and stress responses in young adult rats

BackgroundAdolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies.MethodsMale and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus.ResultsThe main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females.ConclusionsThis study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.