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Purpose: Reduced capillary number in skeletal muscle due to disuse can hinder the delivery of insulin and amino acid delivery to muscle cells, diminishing insulin activity and muscle protein synthesis, ultimately contributing to anabolic resistance. However, it remains unknown whether mitigating capillary regression during inactivity improves anabolic resistance. This study aimed to investigate the effect of increasing capillary number through the administration of prazosin, which can increase blood flow and prevent capillary regression, on anabolic resistance in skeletal muscle induced by disuse., Methods: Male Sprague Dawley rats were divided into control and hindlimb unloading (HU) groups, with half of each group receiving prazosin (50 mg/L) in their drinking water for 2 weeks. Histological analysis of the soleus muscles was conducted to measure the capillary-to-fiber (C/F) ratio, while western blotting was performed to measure the activation of the Akt/mTORC1 muscle protein synthesis pathway before and after insulin stimulation., Results: The C/F ratios were significantly lower in the HU and HU + Prz groups than in the control group but were significantly higher in the HU + Prz group than in the HU group. Following insulin stimulation, the phosphorylation levels of Akt, p70S6K, and S6RP increased in all groups, with a significantly greater increase observed in the HU + Prz group compared to the HU group, indicating improved molecular signaling related to muscle protein synthesis., Conclusion: Administration of prazosin during hindlimb unloading mitigated capillary regression and enhanced insulin-stimulated muscle protein synthesis response. These findings suggest that enhancing capillary number may reduce the anabolic resistance caused by muscle disuse., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01454-y., Competing Interests: Disclosure of conflicts of interestThe authors declared that they have no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Perovskite oxyhydrides have attracted recent attention due to their intriguing properties such as ionic conductivity and catalysis, but their repertoire is still restricted compared to perovskite oxynitrides and oxyfluorides. Historically, perovskite oxyhydrides have been prepared mostly by topochemical reactions and high-pressure (HP) reactions, while in this study, we employed a mechanochemical (MC) approach, which enables the synthesis of a series of AB O 2 H-type oxyhydrides, including those with the tolerance factor ( t ) much smaller than 1 (e.g., SrScO 2 H with t = 0.936) which cannot be obtained by HP synthesis. The octahedral tilting, often present in perovskite oxides, does not occur, suggesting that the lack of π-symmetry of the H 1s orbital and the large polarization destabilize tilted low-symmetry structures. Interestingly, SrCrO 2 H ( t = 0.997), previously reported with the HP method, was not achieved with the MC method. A comparative analysis revealed a correlation between the feasibility of MC reactions and the (calculated) shear modulus of the starting reagents (binary oxides and hydrides). Notably, this indicator is not exclusive to oxyhydride perovskites but extends to oxide perovskites (Sr M O 3 ). This study demonstrates that MC synthesis offers unique opportunities not only to expand the compositional space in oxyhydrides in various structural types but also to provide a guide for the choice of starting materials for the synthesis of other compounds.

The external urethral sphincter (EUS) is crucial in urinary continence development. Understanding the morphological features of the EUS in female rats after vaginal distention (VD), using a model of birth trauma, would aid in evaluating its functional and metabolic properties. Our recent study demonstrated that the EUS in female rats expresses one slow (type 1) and two fast (types 2A and 2B) myosin heavy chain (MHC) isoforms. Our preliminary experiment revealed that type 2B isoform expression was markedly reduced in the EUS 4 weeks after VD. Here, we aimed to examine the expression patterns of these three types of MHC isoforms, and an embryonic MHC, a marker of regeneration fibers, in the EUS of rats 3 days and 1, 2, and 8 weeks after VD using immunofluorescence staining. Hence, type 2B fibers were selectively damaged early in post-VD and did not recover fully later. Muscle regeneration in the sphincter peaked 1 week after trauma using a marker of immature fibers, embryonic myosin heavy chain. Electron microscopy revealed that the EUS of female rats was composed of mitochondria-rich muscle fibers. Myoblasts or immature muscle fibers were discovered in the sphincter layer 1 week after trauma. These results suggest that myogenesis after VD may not contribute to restoring normal fiber composition in a female rat's EUS., (© 2023 American Association for Anatomy.)

Typically, transition metals are considered as the centers for the activation of dinitrogen. Here we demonstrate that the nitride hydride compound Ca 3 CrN 3 H, with robust ammonia synthesis activity, can activate dinitrogen through active sites where calcium provides the primary coordination environment. DFT calculations also reveal that an associative mechanism is favorable, distinct from the dissociative mechanism found in traditional Ru or Fe catalysts. This work shows the potential of alkaline earth metal hydride catalysts and other related 1 D hydride/electrides for ammonia synthesis., (© 2023 Wiley-VCH GmbH.)

Topochemical reactions have led to great progress in the discovery of new metastable compounds with novel chemical and physical properties. With these reactions, the overall crystal structure of the host material is generally maintained. Here we report a topochemical synthesis of a hexagonal nitride hydride, h-Ca 3 CrN 3 H, by heating an orthorhombic nitride, o-Ca 3 CrN 3 , under hydrogen at 673 K, accompanied by a rotational structural transformation. The hydrogen intercalation modifies the Ca-N rock-salt-like atomic packing in o-Ca 3 CrN 3 to a face-sharing octahedral chain in h-Ca 3 CrN 3 H, mimicking a "hinged tessellation" movement. In addition, the h-Ca 3 CrN 3 H exhibited stable ammonia synthesis activity when used as a catalyst., (© 2022 Wiley-VCH GmbH.)

Background: Severe neonatal hyperbilirubinemia has been known to cause the clinical syndrome of kernicterus and a milder one the syndrome of bilirubin-induced neurologic dysfunction (BIND). BIND clinically manifests itself after the neonatal period as developmental delay, cognitive impairment, and related behavioral and psychiatric disorders. The complete picture of BIND is not clear., Methods: The Gunn rat is a mutant strain of the Wistar rat with the BIND phenotype, and it demonstrates abnormal behavior. We investigated serotonergic dysfunction in Gunn rats by pharmacological analyses and ex vivo neurochemical analyses., Results: Ketanserin, the 5-HT2AR antagonist, normalizes hyperlocomotion of Gunn rats. Both serotonin and its metabolites in the frontal cortex of Gunn rats were higher in concentrations than in control Wistar rats. The 5-HT2AR mRNA expression was downregulated without alteration of the protein abundance in the Gunn rat frontal cortex. The TPH2 protein level in the Gunn rat raphe region was significantly higher than that in the Wistar rat., Conclusions: It would be of value to be able to postulate that a therapeutic strategy for BIND disorders would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after onset of BIND manifestations., Impact: We demonstrated serotonergic dysregulation underlying hyperlocomotion in Gunn rats. This finding suggests that a therapeutic strategy for bilirubin-induced neurologic dysfunction (BIND) would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after the onset of the BIND manifestations. Ketanserin normalizes hyperlocomotion of Gunn rats. To our knowledge, this is the first study to demonstrate a hyperlocomotion link to serotonergic dysregulation in Gunn rats., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. Importantly, these alterations in GABAergic neurons are not global, which means they are more prevalent among distinct subclasses of interneurons, including those that express the calcium binding protein parvalbumin. A decreased expression of parvalbumin in the hippocampus is a consistent observation not only in postmortem human schizophrenia patients, but also in a diverse number of rodent models of the disease. Meanwhile, previously we reported that the congenital hyperbilirubinemia model rats (Gunn rats), which is a mutant of the Wistar strain, showed behavioral abnormalities, for instance, hyperlocomotor activity, deficits of prepulse inhibition, inappropriate social interaction, impaired recognition memory similar with several rodent models of schizophrenia. Several animal studies linked the importance of palvalbumin in relation to abnormal hippocampal activity and schizophrenia-like behavior. Here, we show that parvalbumin positive cell density was significantly lower in the CA1, CA3 and the total hippocampus of Gunn rats (congenital hyperbilirubinemia model rats) compared to Wistar control rats. The correlations between serum UCB levels and loss of PV expression in the hippocampus were also detected. The decreases in the PV-expression in the hippocampus might suggest an association of the behavioral abnormalities as schizophrenia-like behaviors of Gunn rats, compared to the Wistar control rats.

Introduction: Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia-like behavior., Methods: As it has been suggested that major depression involves glial activation associated with neuroinflammation, we examined whether Gunn rats show depression-like behavior using the forced swimming test (FST) and the tail suspension test (TST). In addition, we quantitatively evaluated both microgliosis and astrogliosis in the hippocampus of Gunn rats using immunohistochemistry analysis of the microglial marker ionized calcium-binding adaptor molecule (Iba) 1 and the astrocytic marker S100B., Results: Both the FST and TST showed that immobility time of Gunn rats was significantly longer than that of normal control Wistar rats, indicating that Gunn rats are somewhat helpless, a sign of depression-like behavior. In the quantification of immunohistochemical analysis, Iba1immunoreactivity in the dentate gyrus (DG), cornu ammonis (CA) 1, and CA3 and the number of Iba1-positive cells in the CA1 and CA3 were significantly increased in Gunn rats compared to Wistar rats. S100B immunoreactivity in the DG, CA1, and CA3 and the number of S100B-positive cells in the DG and CA3 were significantly increased in Gunn rats compared to Wistar rats., Conclusion: Our findings suggest that both microglia and astrocyte are activated in Gunn rats and their learned helplessness could be related to glial activation., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

The external urethral sphincter is a unique striated muscle surrounding the urethra that plays a crucial role in urinary continence, and a comprehensive understanding of its morphology is needed to determine the pathophysiology underlying urinary incontinence and find suitable therapies. Differences between the sexes and among species regarding the fiber types present remain controversial. This study used triple immunofluorescence labeling to visualize one slow (Type 1) and two fast (Types 2A and 2B) myosin isoforms in rat external urethral sphincters from both sexes. Type 2A fibers predominated throughout the sphincter and Type 2B fibers were restricted to the proximal one-third of the external urethral sphincter in the female rats. Type 1 fibers were present adluminally and were concentrated in the proximal and distal segments of the sphincter. While most of the male external urethral sphincter comprised Type 2B fibers, Type 2A fibers intermingled among these fibers in the proximal one-third of the sphincter, and a few Type 1 fibers were present that were restricted to the adluminal region of the proximal segment. The fiber-type compositions and their areal densities changed in both sexes after gonadectomy. The areal density of the Type 1 fibers increased significantly in the ovariectomized females, especially in the distal segment. In the orchidectomized males, the areal densities of the Types 1 and 2A fibers increased significantly, but that of the Type 2B fibers decreased. These results indicate that myosin heavy chain expression in the rat external urethral sphincter is sexually dimorphic and shows regional differences. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2058-2069, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+), suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.

Background: Accumulating evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. We previously reported evidence of schizophrenia-like behaviors and microglial activation in Gunn rats. We concluded that the Gunn rat, which exhibits a high concentration of unconjugated bilirubin, may be useful as an animal model of schizophrenia. On the other hand, there have been numerous reports that minocycline is effective in treating schizophrenia., Methods: In the present study, we investigated the effects of minocycline on performance of behavioral tests (prepulse inhibition (PPI) and novel object recognition test (NORT)) after animals received either 40mg/kg/d of minocycline or vehicle by intraperitoneal (i.p.) injection for 14 consecutive days. Furthermore, we examined the effects of minocycline on microglial activation in the hippocampal dentate gyrus of Gunn rats and Wistar rats., Results: We found that administration of minocycline for 14days significantly increased the exploratory preference in retention sessions and tended to improve the PPI deficits in Gunn rats. Immunohistochemistry analysis revealed that microglial cells in the minocycline-treated Gunn rat group showed less expression of CD11b compared to vehicle-treated Gunn and Wistar groups., Conclusions: Our findings suggest that minocycline improves recognition memory and attenuates microglial activation in the hippocampal dentate gyrus of Gunn rats. Therefore, minocycline may be a potential therapeutic drug for schizophrenia., (Copyright © 2013. Published by Elsevier Inc.)

Background: The pathophysiology of schizophrenia (SCZ) remains unclear, and its treatment is far from ideal. We have previously reported that yokukansan (YKS), which is a traditional Japanese medicine, is effective as an adjunctive therapy for SCZ. However, the mechanisms underlying the action of YKS have not yet been completely elucidated. A recent meta-analysis study has shown that adjuvant anti-inflammatory drugs are effective for SCZ treatment, and it has been proposed that some of the cognitive deficits associated with inflammation may in part be related to inflammation-induced reductions in adult hippocampal neurogenesis. Although certain ingredients of YKS have potent anti-inflammatory activity, no study has determined if YKS has anti-inflammatory properties., Methods: Using the Gunn rat, which has been reported as a possible animal model of SCZ, we investigated whether YKS affects cognitive dysfunction in an object-location test and the suppression of microglial activation and neurogenesis in the hippocampus., Results: We found that YKS ameliorated spatial working memory in the Gunn rats. Furthermore, YKS inhibited microglial activation and promoted neurogenesis in the hippocampal dentate gyrus of these rats. These results suggest that the ameliorative effects of YKS on cognitive deficits may be mediated in part by the suppression of the inflammatory activation of microglia., Conclusions: These findings shed light on the possible mechanism underlying the efficacy of YKS in treating SCZ.

Melanocortin-4 receptor (MC4R)-expressing neurons are widely distributed in the central nervous system and play a crucial role in a variety of physiological functions including energy and glucose/insulin homeostasis. However, their neural pathways remain to be elucidated. In the present study, we examined a possible pathway from MC4R-expressing neurons in the dorsal motor nucleus of the vagus nerve (DMV) to the intrapancreatic ganglia using transgenic mice that express green fluorescent protein (GFP) under the control of the MC4R-promoter. Using immunofluorescence labeling, we demonstrated that GFP-immunoreactive (ir) nerve fibers were distributed in the intrapancreatic ganglia closely associated with the islets as well as among the acini. These GFP-ir fibers with bouton-like varicosities were frequently observed to surround ganglion cells immunoreactive for vasoactive intestinal polypeptide, a marker for postganglionic parasympathetic neurons. Using the pre-embedding immunoperoxidase method, we clearly showed that GFP-ir terminals formed synapses predominantly with dendrites and additionally with somata of the ganglion cells. Moreover, bilateral subdiaphragmatic vagotomy caused a marked loss of GFP immunoreactivity in the pancreas. Using a combination of retrograde tracing and immunohistochemistry, we finally demonstrated that nearly half of the pancreas-projecting DMV neurons were immunoreactive for GFP. These results suggest that MC4R-expressing DMV neurons may participate in the regulation of glucose/insulin homeostasis through their projections to the intrapancreatic ganglia., (© 2013 Elsevier B.V. All rights reserved.)

Shimane University has started to provide facilities and services to female researchers and healthcare staff who have worked for the university or its hospital after 2007. This initiative had been supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology until 2010. Over time, it has become clear that these efforts, including a day-and-night nursery, day-care for sick children, temporary day-care, after-school programs, and research support system have effectively sustained female researchers and staff in maintaining a balance between private life and work. It is essential that the university devote part of its budget along with outside funding for continued childcare, which has so motivated these female employees. Moreover, it is expected that these efforts will become an effective recruitment tool for excellent young teachers and researchers.

Melanin-concentrating hormone (MCH) is involved in the regulation of feeding behavior as well as in goal oriented behaviors, and MCH-containing neurons are distributed mainly in the lateral hypothalamic area (LHA). The anterior basomedial nucleus (BMA) and anterior cortical nucleus (CoA) of the amygdala form part of a circuit involved in processing olfactory, gustatory and visceral information, and the BMA-LHA and CoA-LHA pathways are suggested to be implicated in the control of feeding behavior. However, it is still unknown whether or not MCH-containing LHA neurons are under the direct influence of the BMA and CoA. Here the organization of projections from the BMA and CoA to MCH-containing LHA neurons was examined. Using a combined anterograde tracing with biotinylated dextranamine and immunohistochemistry for MCH, we first demonstrated that the distribution pattern of BMA fibers was almost similar to that of CoA fibers in the LHA, and a prominent overlapping distribution of these fibers and MCH-immunoreactive neurons existed in the ventral peripeduncular region of the LHA. We further revealed that asymmetrical synapses were made between these fibers and neurons. Using a combination of retrograde tract-tracing with cholera toxin B subunit and in situ hybridization for vesicular glutamate transporter (VGLUT) 2 mRNA, we finally showed that most of the LHA-projecting BMA and CoA neurons expressed VGLUT2 mRNA. These data suggest that the BMA and CoA of the amygdala may exert excitatory influence upon the MCH-containing LHA neurons for the regulation of feeding behavior., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The neural pathways underlying the respiratory responses elicited by electrical or chemical stimulation of the lateral part of the periaqueductal gray (lPAG) remain unsettled. In the present study, we examined the lPAG projection to neurokinin-1 receptor (NK1R)-immunoreactive (ir) neurons in the ventrolateral medulla (VLM) which have been implicated in the control of respiration. After biotinylated dextranamine (BDA) injection into the lPAG, NK1R-ir neurons in the rostral VLM were embedded in the plexus of BDA-labeled fibers. At the electron microscopic level, the BDA-labeled terminals made asymmetrical synaptic contacts predominantly with dendrites and additionally with somata of the NK1R-ir neurons. Using retrograde tracing combined with in situ hybridization, we demonstrated that the vast majority of the lPAG neurons projecting to the rostral VLM were positive for vesicular glutamate transporter 2 (VGLUT2) mRNA, but not for glutamic acid decarboxylase 67 mRNA. Using a combination of anterograde tracing and immunohistochemistry, we further demonstrated that the lPAG axon terminals with VGLUT2 immunoreactivity made close apposition with the NK1R-ir neuronal profiles in the rostral VLM. These data suggest that lPAG neurons exert an excitatory influence on NK1R-expressing neurons in the rostral VLM for the control of respiration., (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Background: Schizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats., Methods: Using immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions. We characterized the microglial cells in the hippocampal dentate gyrus., Results: We found that microglial cells showed activated morphology in the hilus, subgranular zone, and granular layer of the Gunn rat hippocampal dentate gyrus. There was no significant difference between cell numbers between in Gunn rats and controls. However, there was significant difference in the area of CD11b expression in the hippocampal dentate gyrus. Ultrastructurally, microglial cells often contained rich enlarged rich organelles in the cytoplasm and showed some phagocytic function., Conclusions: We propose that activation of microglia could be an important causal factor of the behavioral abnormalities and neuropathological changes in Gunn rats. These findings may provide basic information for further assessment of the Gunn rat as an animal model of schizophrenia.