Impact of daily administration of blackberry extract on gerbil model of transient cerebral ischemia.

PURPOSE: Blackberries are rich in polyphenols and are a human health food continuously consumed to improve health and reduce diseases caused by aging. Herein, we evaluated the effects of daily blackberry administration before and after transient cerebral ischemia in gerbils. METHODS: Blackberry extract (BBE) was orally administered twice a day for two weeks to protect against ischemic events during continuous administration. On the seventh day after administration, the bilateral common carotid arteries were transiently occluded for 5 min. To verify its therapeutic effect, BBE was administered after ischemia using a similar protocol without pre-administration. In both experiments, the number of viable neurons in the CA1 region of the hippocampus was assessed seven days after ischemic treatment. RESULTS: The number of neurons in the group treated with BBE before ischemia was higher than that in the group treated with distilled water (p = 0.0601), and similar to that in the control group. In the BBE administration experiments after ischemia, the number of neurons was significantly reduced compared to that in the control group (p < 0.0001). CONCLUSIONS: Continuous BBE intake is expected to prevent or ameliorate ischemic events such as transient cerebral ischemia.

Multispecies initial numerical validation of an efficient algorithm prototype for auditory brainstem response hearing threshold estimation.

The auditory brainstem response (ABR) can be used to evaluate hearing sensitivity of animals. However, typical measurement protocols are time-consuming. Here, an adaptive algorithm is proposed for efficient ABR threshold estimation. The algorithm relies on the update of the predicted hearing threshold from a Gaussian process model as ABR data are collected using iteratively optimized stimuli. To validate the algorithm, ABR threshold estimation is simulated by adaptively subsampling pre-collected ABR datasets. The simulated experiment is performed on 5 datasets of mouse, budgerigar, gerbil, and guinea pig ABRs (27 ears). The datasets contain 68-106 stimuli conditions, and the adaptive algorithm is configured to terminate after 20 stimuli conditions. The algorithm threshold estimate is compared against human rater estimates who visually inspected the full waveform stacks. The algorithm threshold matches the human estimates within 10 dB, averaged over frequency, for 15 of the 27 ears while reducing the number of stimuli conditions by a factor of 3-5 compared to standard practice. The intraclass correlation coefficient is 0.81 with 95% upper and lower bounds at 0.74 and 0.86, indicating moderate to good reliability between human and algorithm threshold estimates. The results demonstrate the feasibility of a Bayesian adaptive procedure for rapid ABR threshold estimation.

Finite-element modelling of interactions of needle with tympanic membrane and middle ear.

The tympanic membrane (TM) is one of the most common routes to access the middle ear and inner ear for the treatment of hearing and balance pathologies. Since the TM is a soft thin biological tissue with small dimensions, using needles seems to be among the most practical interventional approaches. In this study, we proposed a finite-element (FE) analysis of needle-TM interactions that combines a 3D model of the TM and other main middle-ear structures in gerbil, and a 2D model of needle insertion into the TM based on the cohesive zone method (CZM). The TM was modelled using a 1st-order Ogden hyperelastic material and its properties were obtained by fitting to the experimental force-displacement plots of large deformation in the TM under needle indentation. The cohesive parameters were also acquired by calibrating the puncture force against the experimental data of needle insertion into the TM. These FE models were then used to obtain the deformation behaviour of the TM and other middle-ear structures due to the insertion force applied at different locations on the TM. Moreover, we investigated the effect of the TM thickness, the geometry of the needle (i.e., diameter and tip angle), and needle material on the insertion of needles into the TM. We also studied the penetration success of deformable needles.

Hypothalamic vasopressin neural densities are higher in male Mongolian gerbils after separation from a pair bond partner and may facilitate behavior to form a new bond.

Although pair bonding has been studied for several decades, only somewhat recently have researchers began studying the neural consequences of separation from a pair bond partner. Here we examined the impact of partner separation on the socially monogamous Mongolian gerbil. Using a within-subjects design, we assessed nonsocial, nonreproductive, and reproductive behavior in male gerbils pre- and post- either 4 weeks of cohabitation with or separation from a pair bond partner. We then conducted an immediate early gene study to examine the influence of partner separation on hypothalamic oxytocin and vasopressin neural responses to interactions with a novel, opposite-sex conspecific.

Retinal neuroanatomy of two emerging model organisms, the spiny mouse (Acomys dimidiatus) and the Mongolian gerbil (Meriones unguiculatus).

Current research using animal models to investigate retinal cell biology and model retinal degenerative diseases largely utilize small mammals that are nocturnal and lack the ability to restore lost vision. In contrast, the Mongolian gerbil (Meriones) is a diurnal rodent with good photopic vision, and the spiny mouse (Acomys) is a small desert-dwelling rodent with remarkable regenerative capabilities. The goal of this study was to identify antibodies that detect retinal cell classes in Meriones and Acomys, and to describe the retinal anatomy of these two species in comparison to outbred laboratory mice (Mus musculus). Immunohistochemistry was performed on retinal sections with antibodies for various retinal cell types. Sections were imaged by light, fluorescence, and confocal microscopy. Cell density, morphology, and placement were compared between species qualitatively and quantitatively. Our analyses revealed a classic assembly of retinal cells in Meriones and Acomys, with a few deviations compared to Mus. Meriones displayed the highest density of cones and Acomys the lowest. A higher density of bipolar cell bodies in the proximal portion of the inner nuclear layer was observed in both Acomys and Meriones compared to Mus, and both species exhibited an increase in amacrine cell density compared to Mus. Our results provide a foundation for future research into the visual system adaptations of these interesting species.

Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci.

Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac®) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K+ channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K+ currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K+ currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 µM fluoxetine notably reduced K+ currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K+ current and revealed a rapidly activating and inactivating K+ current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K+ currents persisted following application of 100 µM fluoxetine. Additionally, marked inhibition of transient inward Na+ currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC50 values were found to be 40 µM and 32 µM for K+ and Na+ currents, respectively. In contrast, 100 µM fluoxetine had no impact on voltage-dependent K+ currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na+ and K+ conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance.

Paradoxical sleep deprivation and restriction promote castration-like effects and local inflammatory responses in male gerbil prostate.

Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR - 96/96 h), and sleep restriction (SR - 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.

Differential patch-leaving behavior during probabilistic foraging in humans and gerbils.

Foraging confronts animals, including humans, with the need to balance exploration and exploitation: exploiting a resource until it depletes and then deciding when to move to a new location for more resources. Research across various species has identified rules for when to leave a depleting patch, influenced by environmental factors like patch quality. Here we compare human and gerbil patch-leaving behavior through two analogous tasks: a visual search for humans and a physical foraging task for gerbils, both involving patches with randomly varying initial rewards that decreased exponentially. Patch-leaving decisions of humans but not gerbils follow an incremental mechanism based on reward encounters that is considered optimal for maximizing reward yields in variable foraging environments. The two species also differ in their giving-up times, and some human subjects tend to overharvest. However, gerbils and individual humans who do not overharvest are equally sensitive to declining collection rates in accordance with the marginal value theorem. Altogether this study introduces a paradigm for a between-species comparison on how to resolve the exploitation-exploration dilemma.

A neural cell automated analysis system based on pathological specimens in a gerbil brain ischemia model.

PURPOSE: Amid rising health awareness, natural products which has milder effects than medical drugs are becoming popular. However, only few systems can quantitatively assess their impact on living organisms. Therefore, we developed a deep-learning system to automate the counting of cells in a gerbil model, aiming to assess a natural product's effectiveness against ischemia. METHODS: The image acquired from paraffin blocks containing gerbil brains was analyzed by a deep-learning model (fine-tuned Detectron2). RESULTS: The counting system achieved a 79%-positive predictive value and 85%-sensitivity when visual judgment by an expert was used as ground truth. CONCLUSIONS: Our system evaluated hydrogen water's potential against ischemia and found it potentially useful, which is consistent with expert assessment. Due to natural product's milder effects, large data sets are needed for evaluation, making manual measurement labor-intensive. Hence, our system offers a promising new approach for evaluating natural products.

Orbitofrontal cortex modulates auditory cortical sensitivity and sound perception in Mongolian gerbils.

Sensory perception is dynamic, quickly adapting to sudden shifts in environmental or behavioral context. Although decades of work have established that these dynamics are mediated by rapid fluctuations in sensory cortical activity, we have a limited understanding of the brain regions and pathways that orchestrate these changes. Neurons in the orbitofrontal cortex (OFC) encode contextual information, and recent data suggest that some of these signals are transmitted to sensory cortices. Whether and how these signals shape sensory encoding and perceptual sensitivity remain uncertain. Here, we asked whether the OFC mediates context-dependent changes in auditory cortical sensitivity and sound perception by monitoring and manipulating OFC activity in freely moving Mongolian gerbils of both sexes under two behavioral contexts: passive sound exposure and engagement in an amplitude modulation (AM) detection task. We found that the majority of OFC neurons, including the specific subset that innervates the auditory cortex, were strongly modulated by task engagement. Pharmacological inactivation of the OFC prevented rapid context-dependent changes in auditory cortical firing and significantly impaired behavioral AM detection. Our findings suggest that contextual information from the OFC mediates rapid plasticity in the auditory cortex and facilitates the perception of behaviorally relevant sounds.

Female Psammomys obesus Are Protected from Circadian Disruption-Induced Glucose Intolerance, Cardiac Fibrosis and Adipocyte Dysfunction.

Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian disruption causes glucose intolerance, cardiac fibrosis and adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur in female P. obesus is unknown. Male and female P. obesus were fed a high energy diet and exposed to a neutral (12 light:12 dark, control) or short (5 light:19 dark, circadian disruption) photoperiod for 20 weeks. Circadian disruption impaired glucose tolerance in males but not females. It also increased cardiac perivascular fibrosis and cardiac expression of inflammatory marker Ccl2 in males, with no effect in females. Females had reduced proapoptotic Bax mRNA and cardiac Myh7:Myh6 hypertrophy ratio. Cardiac protection in females occurred despite reductions in the clock gene Per2. Circadian disruption increased adipocyte hypertrophy in both males and females. This was concomitant with a reduction in adipocyte differentiation markers Pparg and Cebpa in males and females, respectively. Circadian disruption increased visceral adipose expression of inflammatory mediators Ccl2, Tgfb1 and Cd68 and reduced browning marker Ucp1 in males. However, these changes were not observed in females. Collectively, our study show that sex differentially influences the effects of circadian disruption on glucose tolerance, cardiac function and adipose tissue dysfunction.

Postnatal zinc deficiency due to giardiasis disrupts hippocampal and cerebellar development.

BACKGROUND: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. METHODS: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. RESULTS: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 µm; HGINV 37 ± 5 µm; WB 28 ± 3 µm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. CONCLUSION: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.

Effects of androgenic modulation on the morphophysiology of the adrenal cortex of male gerbils.

The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERß. Castration promoted an increase in the CYP19, while decreasing 17ßHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3ßHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland.

Exercise Reduces Glucose Intolerance, Cardiac Inflammation and Adipose Tissue Dysfunction in Psammomys obesus Exposed to Short Photoperiod and High Energy Diet.

Circadian disruption causes glucose intolerance, cardiac fibrosis, and adipocyte dysfunction in sand rats (Psammomys obesus). Exercise intervention can improve glucose metabolism, insulin sensitivity, adipose tissue function and protect against inflammation. We investigated the influence of exercise on male P. obesus exposed to a short photoperiod (5 h light:19 h dark) and high-energy diet. Exercise reduced glucose intolerance. Exercise reduced cardiac expression of inflammatory marker Ccl2 and Bax:Bcl2 apoptosis ratio. Exercise increased heart:body weight ratio and hypertrophy marker Myh7:Myh6, yet reduced Gata4 expression. No phenotypic changes were observed in perivascular fibrosis and myocyte area. Exercise reduced visceral adipose expression of inflammatory transcription factor Rela, adipogenesis marker Ppard and browning marker Ppargc1a, but visceral adipocyte size was unaffected. Conversely, exercise reduced subcutaneous adipocyte size but did not affect any molecular mediators. Exercise increased ZT7 Bmal1 and Per2 in the suprachiasmatic nucleus and subcutaneous Per2. Our study provides new molecular insights and histological assessments on the effect of exercise on cardiac inflammation, adipose tissue dysfunction and circadian gene expression in P. obesus exposed to short photoperiod and high-energy diet. These findings have implications for the protective benefits of exercise for shift workers in order to reduce the risk of diabetes and cardiovascular disease.

Vagus Nerve Suppression in Ischemic Stroke by Carotid Artery Occlusion: Implications for Metabolic Regulation, Cognitive Function, and Gut Microbiome in a Gerbil Model.

The vagus nerve regulates metabolic homeostasis and mediates gut-brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut-brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut-brain axis. Targeting the gut-brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke.

Involvement of the gut microbiota in the metabolic phenotypes of two sympatric gerbils.

Temporal niche partitioning is a crucial strategy for sympatric species to avoid predation and competition for habitat space and food resources. This study investigated the effect of the gut microbiota on the metabolic rhythms of two sympatric gerbil species (Meriones unguiculatus and Meriones meridianus) to test the hypothesis that the oscillatory patterns of microbiota may not fully mirror those of the host's metabolism. Experiment 1 compared the circadian metabolic and gut microbiota rhythms of M. unguiculatus (n = 12) and M. meridianus (n = 12) and measured the subjects' body temperatures and environmental temperature preferences. In Experiment 2.1, six M. meridianus gerbils were treated with antibiotics, and in Experiment 2.2, 21 M. unguiculatus gerbils (seven per treatment) were randomly gavaged with saline or a gut microbiota suspension from either M. unguiculatus or M. meridianus; their metabolic rhythms were subsequently measured. The results showed that the two gerbils had different metabolic phenotypes that determined activity heterogeneity and contributed to their coexistence. The relative abundances of Bacteroidetes, Actinobacteria, and Cyanobacteria in M. meridianus varied rhythmically in parallel with the daily metabolic rate, which was significantly higher at night than during the day. The rhythm of the metabolic rate was not noticeable in M. unguiculatus. However, in M.unguiculatus, the relative abundances of Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were significantly higher during the day than at night, while Cyanobacteria exhibited the opposite pattern. Antibiotic treatment significantly weakened the metabolic rhythms of M. meridianus, and the circadian rhythms slowly recovered after stopping antibiotic gavage. However, after transplanting M. meridianus' gut microbiota into M. unguiculatus, the metabolic rate of M. unguiculatus was not significantly different from that of the control groups. Our hypothesis was partly supported: the microbiota was only partially involved in regulating the metabolic rhythms of gerbils, and other factors could compensate for the effect of the gut microbiota on host metabolic rhythms. This finding underscores the complexity of host-microbiota interactions and highlights the need for further exploration into the multifaceted mechanisms governing host metabolic regulation.

Heterogeneous spatial tuning in the auditory pathway of the Mongolian Gerbil (Meriones unguiculatus).

Sound-source localization is based on spatial cues arising due to interactions of sound waves with the torso, head and ears. Here, we evaluated neural responses to free-field sound sources in the central nucleus of the inferior colliculus (CIC), the medial geniculate body (MGB) and the primary auditory cortex (A1) of Mongolian gerbils. Using silicon probes we recorded from anaesthetized gerbils positioned in the centre of a sound-attenuating, anechoic chamber. We measured rate-azimuth functions (RAFs) with broad-band noise of varying levels presented from loudspeakers spanning 210° in azimuth and characterized RAFs by calculating spatial centroids, Equivalent Rectangular Receptive Fields (ERRFs), steepest slope locations and spatial-separation thresholds. To compare neuronal responses with behavioural discrimination thresholds from the literature we performed a neurometric analysis based on signal-detection theory. All structures demonstrated heterogeneous spatial tuning with a clear dominance of contralateral tuning. However, the relative amount of contralateral tuning decreased from the CIC to A1. In all three structures spatial tuning broadened with increasing sound-level. This effect was strongest in CIC and weakest in A1. Neurometric spatial-separation thresholds compared well with behavioural discrimination thresholds for locations directly in front of the animal. Our findings contrast with those reported for another rodent, the rat, which exhibits homogenous and sharply delimited contralateral spatial tuning. Spatial tuning in gerbils resembles more closely the tuning reported in A1 of cats, ferrets and non-human primates. Interestingly, gerbils, in contrast to rats, share good low-frequency hearing with carnivores and non-human primates, which may account for the observed spatial tuning properties.

A preoperative dose of the pyridoindole AC102 improves the recovery of residual hearing in a gerbil animal model of cochlear implantation.

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. In a gerbil animal model of CI, AC102 significantly improves the recovery of hearing thresholds across multiple frequencies and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. In vitro experiments in an ethanol challenged HT22 cell-line revealed significant and dose-responsive anti-apoptotic effects following the treatment of with AC102. Further, AC102 treatment resulted in significant downregulation of the expression of pro-inflammatory cytokines in an organotypic ex vivo model of electrode insertion trauma (EIT). These results suggest that AC102's effects are likely elicited during the inflammatory phase of EIT and mediated by anti-apoptotic and anti-inflammatory properties, highlighting AC102 as a promising compound for hearing preservation during CI. Moreover, since the inflammatory response in CI shares similarities to that in other etiologies of SNHL, AC102 may be inferred as a potential general treatment option for various inner ear conditions.

Helicobacter pylori-Induced Decrease in Membrane Expression of Na,K-ATPase Leads to Gastric Injury.

Helicobacter pylori is a highly prevalent human gastric pathogen that causes gastritis, ulcer disease, and gastric cancer. It is not yet fully understood how H. pylori injures the gastric epithelium. The Na,K-ATPase, an essential transporter found in virtually all mammalian cells, has been shown to be important for maintaining the barrier function of lung and kidney epithelia. H. pylori decreases levels of Na,K-ATPase in the plasma membrane of gastric epithelial cells, and the aim of this study was to demonstrate that this reduction led to gastric injury by impairing the epithelial barrier. Similar to H. pylori infection, the inhibition of Na,K-ATPase with ouabain decreased transepithelial electrical resistance and increased paracellular permeability in cell monolayers of human gastric cultured cells, 2D human gastric organoids, and gastric epithelium isolated from gerbils. Similar effects were caused by a partial shRNA silencing of Na,K-ATPase in human gastric organoids. Both H. pylori infection and ouabain exposure disrupted organization of adherens junctions in human gastric epithelia as demonstrated by E-cadherin immunofluorescence. Functional and structural impairment of epithelial integrity with a decrease in Na,K-ATPase amount or activity provides evidence that the H. pylori-induced downregulation of Na,K-ATPase plays a role in the complex mechanism of gastric disease induced by the bacteria.

The Helicobacter pylori infection alters the intercellular junctions on the pancreas of gerbils (Meriones unguiculatus).

Helicobacter pylori is a common resident in the stomach of at least half of the world's population and recent evidence suggest its emergence in other organs such as the pancreas. In this organ, the presence of H. pylori DNA has been reported in cats, although the functional implications remain unknown. In this work, we determined distinct features related to the H. pylori manifestation in pancreas in a rodent model, in order to analyse its functional and structural effect. Gerbils inoculated with H. pylori exhibited the presence of this bacterium, as revealed by the expression of some virulence factors, as CagA and OMPs in stomach and pancreas, and confirmed by urease activity, bacterial culture, PCR and immunofluorescence assays. Non-apparent morphological changes were observed in pancreatic tissue of infected animals; however, delocalization of intercellular junction proteins (claudin-1, claudin-4, occludin, ZO-1, E-cadherin, ß-catenin, desmoglein-2 and desmoplakin I/II) and rearrangement of the actin-cytoskeleton were exhibited. This structural damage was consistent with alterations in the distribution of insulin and glucagon, and a systemic inflammation, event demonstrated by elevated IL-8 levels. Overall, these findings indicate that H. pylori can reach the pancreas, possibly affecting its function and contributing to the development of pancreatic diseases.