Disparities in Body Color Adaptability and Ambient Light Color Preference between Wild and Hatchery-Reared Marbled Rockfish (Sebastiscus marmoratus).

Hatchery rearing significantly influences the phenotypic development of fish, with potential adverse effects for the post-release performance of hatchery-reared individuals in natural environments, especially when targeted for stock enhancement. To assess the suitability of releasing hatchery-reared fish, a comprehensive understanding of the phenotypic effects of captive rearing, through comparisons with their wild conspecifics, is essential. In this study, we investigated the divergence in body coloration between wild and hatchery-reared marbled rockfish Sebastiscus marmoratus. We examined the selection preferences for different light colors and assessed the impact of different ambient light colors on the morphological color-changing ability of juvenile marbled rockfish. Our findings revealed significant differences in body color between wild and hatchery-reared marbled rockfish. The hue and saturation values of wild marbled rockfish were significantly higher than those of their hatchery-reared counterparts, indicative of deeper and more vibrant body coloration in the wild population. Following a ten-day rearing period under various light color environments, the color of wild marbled rockfish remained relatively unchanged. In contrast, hatchery-reared marbled rockfish tended to change their color, albeit not reaching wild-like coloration. Light color preference tests demonstrated that wild juvenile marbled rockfish exhibited a preference for a red-light environment, while hatchery-reared individuals showed a similar but weaker response. Both wild and hatchery-reared marbled rockfish displayed notable negative phototaxis in the presence of yellow and blue ambient light. These results highlight the impact of hatchery rearing conditions on the body color and morphological color-changing ability, and provide insight into light color selection preferences of marbled rockfish. To mitigate the divergence in phenotypic development and produce more wild-like fish for stocking purposes, modifications to the hatchery environment, such as the regulation of ambient light color, should be considered.

Ketogenic diet attenuates cognitive dysfunctions induced by hypoglycemia via inhibiting endoplasmic reticulum stress-dependent pathways.

Hypoglycemia can potentially cause severe damage to the central nervous system. The ketogenic diet (KD), characterized by high-fat and extremely low-carbohydrate content, can modulate homeostasis and nutrient metabolism, thereby influencing body health. However, the effects and underlying mechanisms of KD on hypoglycemia-induced brain injury have not been thoroughly investigated. We aimed to explore the modulating effects of KD on cognitive functions and elucidate the underlying mechanisms. In this study, one-month-old mice were fed with KD for 2 weeks, and the changes in the gut microbiota were detected using the 16S rRNA gene amplicon sequencing method. The hypoglycemic model of mice was established using insulin, and the potential protective effect of KD on hypoglycemia-induced brain injury in mice was evaluated through immunofluorescence staining, western blotting, transmission electron microscopy, and Golgi staining. Our results showed that the intestinal flora of Dorea increased and Rikenella decreased in KD-fed mice. KD can not only alleviate anxiety-like behavior induced by hypoglycemia, but also increase the proportion of mushroom dendritic spines in the hippocampus by modulating changes in the gut microbiota. KD regulated synaptic plasticity by increasing the levels of SPN, PSD95, and SYP, which relieve cognitive impairment caused by hypoglycemia. Moreover, KD can promote the proliferation and survival of adult neural stem cells in the hippocampus, while reducing apoptosis by suppressing the activation of the IRE1-XBP1 and ATF6 endoplasmic reticulum stress pathways in mice with hypoglycemia. This study provides new evidence for demonstrating that KD may alleviate cognitive dysfunctions caused by hypoglycemia by modulating the gut microbiota.

Unbalanced diets enhance the complexity of gut microbial network but destabilize its stability and resistance.

Stability is a fundamental ecological property of the gut microbiota and is associated with host health. Numerous studies have shown that unbalanced dietary components disturb the gut microbial composition and thereby contribute to the onset and progression of disease. However, the impact of unbalanced diets on the stability of the gut microbiota is poorly understood. In the present study, four-week-old mice were fed a plant-based diet high in refined carbohydrates or a high-fat diet for four weeks to simulate a persistent unbalanced diet. We found that persistent unbalanced diets significantly reduced the gut bacterial richness and increased the complexity of bacterial co-occurrence networks. Furthermore, the gut bacterial response to unbalanced diets was phylogenetically conserved, which reduced network modularity and enhanced the proportion of positive associations between community taxon, thereby amplifying the co-oscillation of perturbations among community species to destabilize gut microbial communities. The disturbance test revealed that the gut microbiota of mice fed with unbalanced diets was less resistant to antibiotic perturbation and pathogenic bacteria invasion. This study may fill a gap in the mechanistic understanding of the gut microbiota stability in response to diet and provide new insights into the gut microbial ecology.

High-fat diet-disturbed gut microbiota-colonocyte interactions contribute to dysregulating peripheral tryptophan-kynurenine metabolism.

BACKGROUND: Aberrant tryptophan (Trp)-kynurenine (Kyn) metabolism has been implicated in the pathogenesis of human disease. In particular, populations with long-term western-style diets are characterized by an excess of Kyn in the plasma. Host-gut microbiota interactions are dominated by diet and are essential for maintaining host metabolic homeostasis. However, the role of western diet-disturbed gut microbiota-colonocyte interactions in Trp metabolism remains to be elucidated. RESULTS: Here, 4-week-old mice were fed with a high-fat diet (HFD), representing a typical western diet, for 4 weeks, and multi-omics approaches were adopted to determine the mechanism by which HFD disrupted gut microbiota-colonocyte interplay causing serum Trp-Kyn metabolism dysfunction. Our results showed that colonocyte-microbiota interactions dominated the peripheral Kyn pathway in HFD mice. Mechanistically, persistent HFD-impaired mitochondrial bioenergetics increased colonic epithelial oxygenation and caused metabolic reprogramming in colonites to support the expansion of Proteobacteria in the colon lumen. Phylum Proteobacteria-derived lipopolysaccharide (LPS) stimulated colonic immune responses to upregulate the indoleamine 2,3-dioxygenase 1 (IDO1)-mediated Kyn pathway, leading to Trp depletion and Kyn accumulation in the circulation, which was further confirmed by transplantation of Escherichia coli (E.coli) indicator strains and colonic IDO1 depletion. Butyrate supplementation promoted mitochondrial functions in colonocytes to remodel the gut microbiota in HFD mice, consequently ameliorating serum Kyn accumulation. CONCLUSIONS: Our results highlighted that HFD disrupted the peripheral Kyn pathway in a gut microbiota-dependent manner and that the continuous homeostasis of gut bacteria-colonocytes interplay played a central role in the regulation of host peripheral Trp metabolism. Meanwhile, this study provided new insights into therapies against western diet-related metabolic disorders. Video Abstract.

Eucommiae cortex polysaccharides attenuate gut microbiota dysbiosis and neuroinflammation in mice exposed to chronic unpredictable mild stress: Beneficial in ameliorating depressive-like behaviors.

BACKGROUND: Chronic stress alters gut microbiota composition, as well as induces inflammatory responses and behavioral deficits. Eucommiae cortex polysaccharides (EPs) have been reported to remodel gut microbiota and ameliorate obesogenic diet-induced systemic low-grade inflammation, but their role in stress-induced behavioral and physiological changes is poorly understood. METHODS: Male Institute of Cancer Research (ICR) mice were exposed to chronic unpredictable stress (CUMS) for 4 weeks and then supplemented with EPs at a dose of 400 mg/kg once per day for 2 weeks. Behavioral test-specific antidepressant and anxiolytic effects of EPs were assessed in FST, TST, EPM, and OFT. Microbiota composition and inflammation were detected using 16S ribosomal RNA (rRNA) gene sequencing, quantitative RT-PCR, western blot, and immunofluorescence. RESULTS: We found that EPs ameliorated gut dysbiosis caused by CUMS, as evidenced by increasing the abundance of Lactobacillaceae and suppressing the expansion of the Proteobacteria, thereby mitigating intestinal inflammation and barrier derangement. Importantly, EPs reduced the release of bacterial-derived lipopolysaccharides (LPS, endotoxin) and inhibited the microglia-mediated TLR4/NFκB/MAPK signaling pathway, thereby attenuating the pro-inflammatory response in the hippocampus. These contributed to restoring the rhythm of hippocampal neurogenesis and alleviating behavioral abnormalities in CUMS mice. Correlation analysis showed that the perturbed-gut microbiota was strongly correlated with behavioral abnormalities and neuroinflammation. LIMITATIONS: This study did not clarify the causal relationship between EPs remodeling the gut microbiota and improved behavior in CUMS mice. CONCLUSIONS: EPs exert ameliorative effects on CUMS-induced neuroinflammation and depression-like symptoms, which may be strongly related to their beneficial effects on gut microbial composition.

Ketogenic Diet Alleviates Hypoglycemia-Induced Neuroinflammation via Modulation the Gut Microbiota in Mice.

SCOPE: This study aims to investigate the role of gut microbiota regulation with ketogenic diet (KD) in hypoglycemia-induced neuroinflammation. METHODS AND RESULTS: Immunofluorescence staining and western blotting show that KD alleviates blood-brain barrier injury induced by hypoglycemia by increasing Podxl and zonula occludens-1 (ZO-1) levels. KD-fed mice show reduced brain edema by decreasing aquaporin-4 (AQP4) content and maintaining its polarized expression. 16S rRNA gene amplicon sequencing results show that KD reduces the Chao 1 index of gut microbiota α-diversity, and significant separation is detected in the ß-diversity analysis between the control and KD-fed mice. KD increases the relative abundance of Firmicutes and Proteobacteria and decreases that of Bacteroidetes. Hypoglycemia can reduce SOD and GSH-PX levels while increasing TNF-α, IL-1ß, and IL-6 mRNA levels in the brain tissues of mice. KD alleviates hypoglycemia-induced neuroinflammation by inhibiting microglia activation and TLR4/p38MAPK/NF-κB signaling pathway. Importantly, antibiotic cocktail depletion of the gut microbiota weakens anti-inflammatory and antioxidation responses in KD-fed mice. CONCLUSION: Collectively, these findings suggest that KD alleviates hypoglycemia-induced brain injury via gut microbiota modulation, which may provide novel insights into the therapy for hypoglycemia.

Dietary Protein Requirement of Juvenile Dotted Gizzard Shad Konosirus punctatus Based on the Variation of Fish Meal.

An 8-week feeding trial was conducted to investigate the effects of dietary protein levels on growth performance, feed utilization, and energy retention of juvenile dotted gizzard shad Konosirus punctatus based on the variation of fish meal. Fish meal was used as the sole protein source; five semi-purified diets were formulated with varying crude protein (CP) levels of 22.52%, 28.69%, 34.85%, 38.84%, 45.78% (CP1-CP5 diets). A total of 300 uniform juveniles with initial body weight 3.61 ± 0.20 g fish-1 were randomly divided into five groups with three replicates in each group. The results showed that different CP levels did not significantly affect the survival of juvenile K. punctatus (p > 0.05). The values of weight gain (WG) and specific growth ratio (SGR) showed a general enhancing trend and then weakened with increasing dietary CP levels (p > 0.05). Feed utilization also improved with increasing dietary CP levels (p > 0.05), and the optimal feed conversion ratio (FCR) value was found in fish fed the diet with CP3 (p > 0.05). The rise of dietary CP from 22.52% to 45.78% enhanced the daily feed intake (DFI) and protein efficiency ratio (PER) values of K. punctatus (p < 0.05). With the increase of dietary CP levels, daily nitrogen intake (DNI), energy retention (ER), and lipid retention (LR) elevated, while retention (NR), daily energy intake (DEI), and daily lipid intake (DLI) reduced (p < 0.05). No statistical differences in the content of water, crude protein, and crude lipid were observed among different treatments (p > 0.05). The activity of lipase in CP3 and CP4 diets was significantly higher than that of the CP1 diet (p < 0.05). Fish fed CP2 and CP3 diets had significantly higher amylase activity than that of the CP5 diet (p < 0.05). The levels of alanine aminotransferase (GPT) first enhanced and then decreased as dietary CP levels raised. The second-order polynomial regression model analysis of the WG and FCR indicated that the optimal dietary protein level for K. punctatus is about 31.75-33.82% based on the variation of fish meal.

Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila.

The gut microbiota is increasingly considered to play a key role in human immunity and health. The aging process alters the microbiota composition, which is associated with inflammation, reactive oxygen species (ROS), decreased tissue function, and increased susceptibility to age-related diseases. It has been demonstrated that plant polysaccharides have beneficial effects on the gut microbiota, particularly in reducing pathogenic bacteria abundance and increasing beneficial bacteria populations. However, there is limited evidence of the effect of plant polysaccharides on age-related gut microbiota dysbiosis and ROS accumulation during the aging process. To explore the effect of Eucommiae polysaccharides (EPs) on age-related gut microbiota dysbiosis and ROS accumulation during the aging process of Drosophila, a series of behavioral and life span assays of Drosophila with the same genetic background in standard medium and a medium supplemented with EPs were performed. Next, the gut microbiota composition and protein composition of Drosophila in standard medium and the medium supplemented with EPs were detected using 16S rRNA gene sequencing analysis and quantitative proteomic analysis. Here, we show that supplementation of Eucommiae polysaccharides (EPs) during development leads to the life span extension of Drosophila. Furthermore, EPs decreased age-related ROS accumulation and suppressed Gluconobacter, Providencia, and Enterobacteriaceae in aged Drosophila. Increased Gluconobacter, Providencia, and Enterobacteriaceae in the indigenous microbiota might induce age-related gut dysfunction in Drosophila and shortens their life span. Our study demonstrates that EPs can be used as prebiotic agents to prevent aging-associated gut dysbiosis and reactive oxidative stress.

Effect of Heat Stress on Hippocampal Neurogenesis: Insights into the Cellular and Molecular Basis of Neuroinflammation-Induced Deficits.

Heat stress is known to result in neuroinflammation, neuronal damage, and disabilities in learning and memory in animals and humans. It has previously been reported that cognitive impairment caused by neuroinflammation may at least in part be mediated by defective hippocampal neurogenesis, and defective neurogenesis has been linked to aberrantly activated microglial cells. Moreover, the release of cytokines within the brain has been shown to contribute to the disruption of cognitive functions in several conditions following neuroinflammation. In this review, we summarize evolving evidence for the current understanding of inflammation-induced deficits in hippocampal neurogenesis, and the resulting behavioral impairments after heat stress. Furthermore, we provide valuable insights into the molecular and cellular mechanisms underlying neuroinflammation-induced deficits in hippocampal neurogenesis, particularly relating to cognitive dysfunction following heat stress. Lastly, we aim to identify potential mechanisms through which neuroinflammation induces cognitive dysfunction, and elucidate how neuroinflammation contributes to defective hippocampal neurogenesis. This review may therefore help to better understand the relationship between hippocampal neurogenesis and heat stress.

Eucommiae cortex polysaccharides mitigate obesogenic diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism.

Rationale: The high fat and sucrose diet, known as the obesogenic diet (OD), has been related to low-grade chronic inflammation and neurodevelopmental disorders. Emerging evidence suggests that OD influences cognitive and social function via the gut-brain axis. However, the effects of OD during adolescence on future health have been unclear. Meanwhile, the underlying mechanisms and effective interventions are not fully understood. Polysaccharides, one of the most abundant substances in the Eucommiae cortex, exhibit potential immunomodulatory and neuroprotective effects. Here, we aimed to investigate the impact of OD on adolescents, explore the modulating roles of Eucommiae cortex polysaccharides (EPs) on OD-induced behavioral dysfunction, and elucidate the underlying molecular mechanisms. Methods: In the present study, four-week-old mice were fed with OD for four weeks to simulate persistent OD in adolescents. The behavioral features were accessed by open field test and Morris water maze. The gut bacterial structure was identified by 16S rRNA gene amplicon sequencing. The gene and protein expression in colonic tissues and hippocampus were detected by qRT-PCR, immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Detection of biological metabolites in serum and hippocampal tissues was performed by widely targeted metabolomics and targeted metabolomics. Results: We found that OD-fed mice showed cognitive and social-behavioral deficits accompanied by gut dysbiosis and systematic tryptophan (Trp) metabolism disorders, which increased kynurenine (Kyn) concentration in the hippocampus. Bacteria-derived lipopolysaccharide (LPS, endotoxin) induced microglia-mediated neuroinflammation, directing the metabolism of Kyn in the hippocampus toward quinolinic acid (QA), which led to glutamate-mediated hyperactivation of mossy cells (MCs) in hippocampal hilus. Furthermore, OD impaired parvalbumin (PV) interneurons-related local circuits in the hippocampal granule cell layer. These resulted in hippocampal neurogenesis deficits and related behavioral dysfunction in mice. EPs supplementation ameliorated OD-induced gut dysbiosis, as evidenced by inhibiting the expansion of Escherichia coli (E.coli) and reducing the concentration of LPS in colonic contents and serum, thereby inhibiting the subsequent neuroinflammation. In addition, oral EPs suppressed the peripheral Kyn pathway to reduce the concentration of QA and glutamic acid in the hippocampus of OD-fed mice, thereby rescuing the glutamic acid-triggered neuroexcitotoxicity. These contributed to remodeling the rhythm of hippocampal neurogenesis and mitigated behavioral dysfunction in OD-fed mice. Conclusions: The present study addresses a gap in the understanding of neuronal dysfunction associated with OD during adolescence and provides the first evidence that EPs improved cognitive and social behavior via modulation of gut microbiota and tryptophan metabolism in adolescent mice fed with OD, which may represent novel preemptive therapy for neurodevelopmental disorders via manipulation of the tryptophan metabolite.

Dietary Supplementation With Acer truncatum Oil Promotes Remyelination in a Mouse Model of Multiple Sclerosis.

Background: Multiple sclerosis is a chronic demyelinating disease of uncertain etiology. Traditional treatment methods produce more adverse effects. Epidemiological and clinical treatment findings showed that unknown environmental factors contribute to the etiology of MS and that diet is a commonly assumed factor. Despite the huge interest in diet expressed by people with MS and the potential role diet plays in MS, very little data is available on the role of diet in MS pathogenesis and MS course, in particular, studies on fats and MS. The oil of Acer truncatum is potential as a resource to be exploited in the treatment of some neurodegenerative diseases. Objective: Here, we investigated the underlying influences of Acer truncatum oil on the stimulation of remyelination in a cuprizone mouse model of demyelination. Methods: Cuprizone (0.2% in chow) was used to establish a mouse model of demyelination. Acer truncatum oil was administrated to mice during remyelination. Following techniques were used: behavioral test, histochemistry, fluorescent immunohistochemistry, transmission electron microscope. Results: Mice exposed to cuprizone for 6 weeks showed schizophrenia-like behavioral changes, the increased exploration of the center in the open field test (OFT), increased entries into the open arms of the elevated plus-maze, as well as demyelination in the corpus callosum. After cuprizone withdrawal, the diet therapy was initiated with supplementation of Acer truncatum oil for 2 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (CC1) and myelin basic protein (MBP). More importantly, the supplementation with Acer truncatum oil in the diet reduced the schizophrenia-like behavior in the open field test (OFT) and the elevated plus-maze compared to the cuprizone recovery group. The results revealed that the diet supplementation with Acer truncatum oil improved behavioral abnormalities, oligodendrocyte maturation, and remyelination in the cuprizone model during recovery. Conclusion: Diet supplementation with Acer truncatum oil attenuates demyelination induced by cuprizone, indicating that Acer truncatum oil is a novel therapeutic diet in demyelinating diseases.

ß-Hydroxybutyric acid attenuates heat stress-induced neuroinflammation via inhibiting TLR4/p38 MAPK and NF-κB pathways in the hippocampus.

Heat stress causes many pathophysiological responses in the brain, including neuroinflammation and cognitive deficits. ß-Hydroxybutyric acid (BHBA) has been shown to have neuroprotective effects against inflammation induced by lipopolysaccharide. The aim of the present study was to evaluate the effects of BHBA on neuroinflammation induced by heat stress, as well as the underlying mechanisms. Mice were pretreated with vehicle, BHBA or minocycline (positive control group) and followed by heat exposure (43°C) for 15 min for 14 days. In mice subjected to heat stress, we found that treatment with BHBA or minocycline significantly decreased the level of serum cortisol, the expressions of heat shock protein 70 (HSP70), and the density of c-Fos+ cells in the hippocampus. Surprisingly, the ethological tests revealed that heat stress led to cognitive dysfunctions and could be alleviated by BHBA and minocycline administration. Further investigation showed that BHBA and minocycline significantly attenuated the activation of microglia and astrocyte induced by heat stress. Pro-inflammatory cytokines were attenuated in the hippocampus by BHBA and minocycline treatment. Importantly, compared with the heat stress group, mice in the BHBA treatment group and positive control group experienced a decrease in the expressions of toll-like receptor 4 (TLR4), phospho-p38 (p-p38), and nuclear factor kappa B (NF-κB). Our results elucidated that BHBA inhibits neuroinflammation induced by heat stress by suppressing the activation of microglia and astrocyte, and modulating TLR4/p38 MAPK and NF-κB pathways. This study provides new evidence that BHBA is a potential strategy for protecting animals from heat stress.

Phosphorylation of Focal Adhesion Kinase at Y925: Role in Glia-Dependent and Independent Migration through Regulating Cofilin and N-Cadherin.

The adult neocortex is a six-layered structure, consisting of nearly continuous layers of neurons that are generated in a temporally strictly coordinated order. During development, cortical neurons originating from the ventricular zone migrate toward the Reelin-containing marginal zone in an inside-out arrangement. Focal adhesion kinase (FAK), one tyrosine kinase localizing to focal adhesions, has been shown to be phosphorylated at tyrosine 925 (Y925) by Src, an important downstream molecule of Reelin signaling. Up to date, the precise molecular mechanisms of FAK and its phosphorylation at Y925 during neuronal migration are still unclear. Combining in utero electroporation with immunohistochemistry and live imaging, we examined the function of FAK in regulating neuronal migration. We show that phosphorylated FAK is colocalized with Reelin positive Cajal-Retzius cells in the developing neocortex and hippocampus. Phosphorylation of FAK at Y925 is significantly reduced in reeler mice. Overexpression and dephosphorylation of FAK impair locomotion and translocation, resulting in migration inhibition and dislocation of both late-born and early-born neurons. These migration defects are highly correlated to the function of FAK in regulating cofilin phosphorylation and N-Cadherin expression, both are involved in Reelin signaling pathway. Thus, fine-tuned phosphorylation of focal adhesion kinase at Y925 is crucial for both glia-dependent and independent neuronal migration.

ß-Hydroxybutyrate Alleviates Low Glucose-Induced Apoptosis via Modulation of ROS-Mediated p38 MAPK Signaling.

Hypoglycemia has emerged as a prominent complication in anti-diabetic drug therapy or negative energy balance of animals, which causes brain damage, cognitive impairment, and even death. Brain injury induced by hypoglycemia is closely related to oxidative stress and the production of reactive oxygen species (ROS). The intracellular accumulation of ROS leads to neuronal damage, even death. Ketone body ß-hydroxybutyrate (BHBA) not only serves as alternative energy source for glucose in extrahepatic tissues, but is also involved in cellular signaling transduction. Previous studies showed that BHBA reduces apoptosis by inhibiting the excessive production of ROS and activation of caspase-3. However, the effects of BHBA on apoptosis induced by glucose deprivation and its related molecular mechanisms have been seldom reported. In the present study, PC12 cells and primary cortical neurons were used to establish a low glucose injury model. The effects of BHBA on the survival and apoptosis in a glucose deficient condition and related molecular mechanisms were investigated by using flow cytometry, immunofluorescence, and western blotting. PC12 cells were incubated with 1 mM glucose for 24 h as a low glucose cell model, in which ROS accumulation and cell mortality were significantly increased. After 24 h and 48 h treatment with different concentrations of BHBA (0 mM, 0.05 mM, 0.5 mM, 1 mM, 2 mM), ROS production was significantly inhibited. Moreover, cell apoptosis rate was decreased and survival rate was significantly increased in 1 mM and 2 mM BHBA groups. In primary cortical neurons, at 24 h after treatment with 2 mM BHBA, the injured length and branch of neurites were significantly improved. Meanwhile, the intracellular ROS level, the proportion of c-Fos+ cells, apoptosis rate, and nuclear translocation of NF-κB protein after treatment with BHBA were significantly decreased when compared with that in low glucose cells. Importantly, the expression of p38, p-p38, NF-κB, and caspase-3 were significantly decreased, while the expression of p-ERK was significantly increased in both PC12 cells and primary cortical neurons. Our results demonstrate that BHBA decreased the accumulation of intracellular ROS, and further inhibited cell apoptosis by mediating the p38 MAPK signaling pathway and caspase-3 apoptosis cascade during glucose deprivation. In addition, BHBA inhibited apoptosis by activating ERK phosphorylation and alleviated the damage of low glucose to PC12 cells and primary cortical neurons. These results provide new insight into the anti-apoptotic effect of BHBA in a glucose deficient condition and the related signaling cascade.

ß-Hydroxybutyric acid improves cognitive function in a model of heat stress by promoting adult hippocampal neurogenesis.

Heat stress has multiple potential effects on the brain, such as neuroinflammation, neurogenesis defects, and cognitive impairment. ß-hydroxybutyric acid (BHBA) has been demonstrated to play neuroprotective roles in various models of neurological diseases. In the present study, we investigated the efficacy of BHBA in alleviating heat stress-induced impairments of adult hippocampal neurogenesis and cognitive function, as well as the underlying mechanisms. Mice were exposed to 43 ℃ for 15 min for 14 days after administration with saline, BHBA, or minocycline. Here, we showed for the first time that BHBA normalized memory ability in the heat stress-treated mice and attenuated heat stress-impaired hippocampal neurogenesis. Consistently, BHBA noticeably improved the synaptic plasticity in the heat stress-treated hippocampal neurons by inhibiting the decrease of synapse-associated proteins and the density of dendritic spines. Moreover, BHBA inhibited the expression of cleaved caspase-3 by suppressing endoplasmic reticulum (ER) stress, and increased the expression of brain-derived neurotrophic factor (BDNF) in the heat stress-treated hippocampus by activating the protein kinase B (Akt)/cAMP response element binding protein (CREB) and methyl-CpG binding protein 2 (MeCP2) pathways. These findings indicate that BHBA is a potential agent for improving cognitive functions in heat stress-treated mice. The action may be mediated by ER stress, and Akt-CREB-BDNF and MeCP2 pathways to improve adult hippocampal neurogenesis and synaptic plasticity.

Prolonged maternal separation alters neurogenesis and synaptogenesis in postnatal dentate gyrus of mice.

OBJECTIVES: As a common model for adverse early experience and depression, maternal separation (MS) is always used to investigate the psychological disease. Despite extensive and strong evidence verified the depression-like state induced by MS, little is known about the specific mechanism of MS. Therefore, the present study aimed to investigate the neurobiology mechanism of the MS-induced depression-like state. METHODS: To verify the depression-like behaviors of offspring induced by MS, a series of behavioral tests were performed. Then, in vivo electroporation and three-dimensional reconstruction, combining with immunohistochemistry and BrdU labeling, were mainly used to explore the neurogenesis and synaptogenesis in postnatal dentate gyrus. RESULTS: Prolonged MS indeed induced the depression-like behaviors of offspring in adulthood. Surprisingly, learning and memory were enhanced by prolonged MS. Further investigation indicated that prolonged MS inhibited the proliferation of neural stem cells, impaired the survival, and altered the fate decision of newborn cells, whereas the total length and terminal tips of dendrite, and the spine density, especially thin spine, were significantly increased in prolonged MS mice. CONCLUSIONS: Our results elucidated that prolonged MS induced the depression-like state by impairing postnatal neurogenesis of dentate gyrus. Importantly, our results emphasized that prolonged MS increased the spine density, especially thin spine, by increasing the total length and number of terminal tips of dendrite, thereby enhancing learning and memory.

Neuroinflammation Induction and Alteration of Hippocampal Neurogenesis in Mice Following Developmental Exposure to Gossypol.

BACKGROUND: Neurogenesis in the neonatal period involves the proliferation and differentiation of neuronal stem/progenitor cells and the establishment of synaptic connections. This process plays a critical role in determining the normal development and maturation of the brain throughout life. Exposure to certain physical or chemical factors during the perinatal period can lead to many neuropathological defects that cause high cognitive dysfunction and are accompanied by abnormal hippocampal neurogenesis and plasticity. As an endocrine disruptor, gossypol is generally known to exert detrimental effects in animals exposed under experimental conditions. However, it is unclear whether gossypol affects neurogenesis in the hippocampal dentate gyrus during early developmental stages. METHODS: Pregnant Institute of Cancer Research mice were treated with gossypol at a daily dose of 0, 20, and 50 mg/kg body weight from embryonic day 6.5 to postnatal day (P) 21. The changes of hippocampal neurogenesis as well as potential mechanisms were investigated by 5-bromo-2-deoxyuridine labeling, behavioral tests, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western-blot analyses. RESULTS: At P8, maternal gossypol exposure impaired neural stem cell proliferation in the dentate gyrus and decreased the number of newborn cells as a result of reduced proliferation of BLBP+ radial glial cells and Tbr2+ intermediate progenitor cells. At P21, the numbers of NeuN+ neurons and parvalbumin+ γ-aminobutyric acid-ergic interneurons were increased following 50 mg/kg gossypol exposure. In addition, gossypol induced hippocampal neuroinflammation, which may contribute to behavioral abnormalities and cognitive deficits and decrease synaptic plasticity. CONCLUSIONS: Our findings suggest that developmental gossypol exposure affects hippocampal neurogenesis by targeting the proliferation and differentiation of neuronal stem/progenitor cells, cognitive functions, and neuroinflammation. The present data provide novel insights into the neurotoxic effects of gossypol on offspring.

Characterization of the complete mitochondrial genome sequence of Nibea diacanthus and its phylogenetic implication.

The blackspotted croaker (Nibea diacanthus) is an important food fish of Indo-West Pacific and China. To study the phylogenetic status, we sequenced the complete mitochondrial genome of N. diacanthus. The mitogenome is 16,532 bp in length and composed of 13 protein-coding genes, two rRNAs, 22 tRNAs, and a control region. The gene composition and the structural arrangement of N. diacanthus complete mtDNA were identical to most of other vertebrates. The phylogenetic analysis using the complete mitochondrial genome revealed that the N. diacanthus might be separated from Nibea genera of Argyrosominae, which was inconsistent with that based on morphology. The complete mitogenome data would be useful for the evolution and conservation genetic studies of Sciaenidae.

Profile of MIF in Developing Hippocampus: Association With Cell Proliferation and Neurite Outgrowth.

Proinflammatory cytokine macrophage migration inhibitory factor (MIF) is a multifunctional cytokine and has been found involved in many neurological diseases such as Alzheimer disease (AD), epilepsy, and multiple sclerosis. Previous studies have shown that MIF is expressed in neocortex, hippocampus, hypothalamus, cerebellum, and spinal cord in adult mice. It is expressed by astrocytes and activates microglias in neuroinflammation. Further studies have shown that MIF is detected in moss fibers of dentate granule cells and in apical dendrites of pyramidal neurons in adult hippocampus. Only NeuroD-positive immature granule neurons but not NeuN-positive mature neurons express MIF. These findings led us eager to know the exact role of MIF in the development of hippocampus. Therefore, we systematically checked the spatial and temporal expression pattern of MIF and characterized MIF-positive cells in hippocampus from mice aged from postnatal day 0 (P0) to 3 months. Our results showed that the lowest level of MIF protein occurred at P7 and mif mRNA increased from P0, reached a peak at P7, and stably expressed until P30 before declining dramatically at 3 months. MIF was localized in fibers of GFAP- and BLBP-positive radial glial precursor cells in dentate gyrus (DG). DCX-expressing newly generated neurons were MIF-negative. Inhibition of MIF by MIF antagonist S, R-3-(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) reduced BrdU-positive cells. Interestingly, MIF was expressed by NeuN-positive GABAergic interneurons including parvalbumin-and Reelin-expressing cells in the DG. Neither NeuN-positive granule cells nor NeuN-positive pyramidal neurons expressed MIF. In transgenic mice, POMC-EGFP-positive immature dentate granule cells and Thy1-EGFP-positive mature granule cells were MIF-negative. Treatment of neuronal cultures with ISO-1 inhibited neurite outgrowth. Therefore, we conclude that MIF might be important for feature maintenance of neural stem cells and neurite outgrowth during hippocampal development.