scholarly journals Regulation of HIF-1α and p53 in stress responses in the subterranean rodents Lasiopodomys mandarinus and Lasiopodomys brandtii (Rodentia: Cricetidae)

2021 ◽  
Vol 38 ◽  
pp. 1-11
Author(s):  
Luye Shi ◽  
Mengwan Jiang ◽  
Mengyang Li ◽  
Xiaozhen Shang ◽  
Xiujuan Li ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Stress Responses ◽  
Adaptation To Hypoxia ◽  
Subterranean Rodents ◽  
Interaction Patterns ◽  
P53 Expression ◽  
Hippocampal Ca1 ◽  
Hypoxic Tolerance ◽  
The Brain ◽  
Lasiopodomys Brandtii

The response mechanism and interaction patterns of HIF-1α and p53 in animals in an hypoxic environment are crucial for their hypoxic tolerance and adaptation. Many studies have shown that underground rodents have better hypoxic adaptation characteristics. However, the mechanism by which HIF-1α and p53 in underground rodents respond to hypoxic environments compared with in ground rodents remains unclear. Further, whether a synergy between HIF-1α and p53 enables animals tolerate extremely hypoxic environments is unclear. We studied HIF-1α and p53 expression in the brain tissue and cell apoptosis in the hippocampal CA1 region during 6 hours of acute hypoxia (5% oxygen) in Lasiopodomys mandarinus (Milne-Edwards, 1871) and Lasiopodomys brandtii (Radde, 1861), two closely related small rodents with different life characteristics (underground and aboveground, respectively), using a comparative biology method to determine the mechanisms underlying their adaptation to this environment. Our results indicate that HIF-1α and p53 expression is more rapid in L. mandarinus than in L. brandtii under acute hypoxic environments, resulting in a significant synergistic effect in L. mandarinus. Correlation analysis revealed that HIF-1α expression and the apoptotic index of the hippocampal CA1 regions of the brain tissues of L. mandarinus and L. brandtii, both under hypoxia, were significantly negatively and positively correlated, respectively. Long-term existence in underground burrow systems could enable better adaptation to hypoxia in L. mandarinus than in L. brandtii. We speculate that L. mandarinus can quickly eliminate resulting damage via the synergistic effect of p53 and HIF-1α in response to acute hypoxic environments, helping the organism quickly return to a normal state after the stress.

scholarly journals Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia

2021 ◽  
Vol 22 (15) ◽  
pp. 7982
Author(s):  
Elena Rybnikova ◽  
Natalia Nalivaeva
Keyword(s):  
Cross Talk ◽  
Glucocorticoid Receptors ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Later Life ◽  
Adaptation To Hypoxia ◽  
Hypoxic Injury ◽  
Hypoxic Tolerance ◽  
Resistance To Stress ◽  
The Brain

Adaptation of organisms to stressors is coordinated by the hypothalamic-pituitary-adrenal axis (HPA), which involves glucocorticoids (GCs) and glucocorticoid receptors (GRs). Although the effects of GCs are well characterized, their impact on brain adaptation to hypoxia/ischemia is still understudied. The brain is not only the most susceptible to hypoxic injury, but also vulnerable to GC-induced damage, which makes studying the mechanisms of brain hypoxic tolerance and resistance to stress-related elevation of GCs of great importance. Cross-talk between the molecular mechanisms activated in neuronal cells by hypoxia and GCs provides a platform for developing the most effective and safe means for prevention and treatment of hypoxia-induced brain damage, including hypoxic pre- and post-conditioning. Taking into account that hypoxia- and GC-induced reprogramming significantly affects the development of organisms during embryogenesis, studies of the effects of prenatal and neonatal hypoxia on health in later life are of particular interest. This mini review discusses the accumulated data on the dynamics of the HPA activation in injurious and non-injurious hypoxia, the role of the brain GRs in these processes, interaction of GCs and hypoxia-inducible factor HIF-1, as well as cross-talk between GC and hypoxic signaling. It also identifies underdeveloped areas and suggests directions for further prospective studies.

scholarly journals Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Stress Responses ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Factor ◽  
Loss Of Function ◽  
P53 Expression ◽  
Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

scholarly journals Polyphenols and IUGR Pregnancies: Effects of the Antioxidant Hydroxytyrosol on Brain Neurochemistry and Development in a Porcine Model

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 884
Author(s):  
Natalia Yeste ◽  
Daniel Valent ◽  
Laura Arroyo ◽  
Marta Vázquez-Gómez ◽  
Consolación García-Contreras ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Porcine Model ◽  
Immunohistochemical Study ◽  
Brain Area ◽  
Fetal Period ◽  
Intrauterine Growth ◽  
Gestational Period ◽  
Hippocampal Ca1 ◽  
Maternal Supplementation ◽  
The Brain

Supplementation of a mother’s diet with antioxidants, such as hydroxytyrosol (HTX), has been proposed to ameliorate the adverse phenotypes of fetuses at risk of intrauterine growth restriction. In the present study, sows were treated daily with or without 1.5 mg of HTX per kilogram of feed from day 35 of pregnancy (at 30% of total gestational period), and individuals were sampled at three different ages: 100-day-old fetuses and 1-month- and 6-month-old piglets. After euthanasia, the brain was removed and the hippocampus, amygdala, and prefrontal cortex were dissected. The profile of the catecholaminergic and serotoninergic neurotransmitters (NTs) was characterized and an immunohistochemical study of the hippocampus was performed. The results indicated that maternal supplementation with HTX during pregnancy affected the NT profile in a brain-area-dependant mode and it modified the process of neuron differentiation in the hippocampal CA1 and GD areas, indicating that cell differentiation occurred more rapidly in the HTX group. These effects were specific to the fetal period, concomitantly with HTX maternal supplementation, since no major differences remained between the control and treated groups in 1-month- and 6-month-old pigs.

Insights into the molecular basis of host behaviour manipulation by Toxoplasma gondii infection

2017 ◽  
Vol 1 (6) ◽  
pp. 563-572 ◽  
Author(s):  
Pierre-Mehdi Hammoudi ◽  
Dominique Soldati-Favre
Keyword(s):  
Toxoplasma Gondii ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Brain Regions ◽  
Intermediate Hosts ◽  
Toxoplasma Gondii Infection ◽  
Host Parasite ◽  
Host Behaviour ◽  
The Brain ◽  
Brain Homeostasis

Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts to enhance transmission to its feline definitive hosts, ensuring survival and dissemination. During the chronic stage of infection in rodents, a variety of neurological dysfunctions have been unravelled and correlated with the loss of cat fear, among other phenotypic impacts. However, the underlying neurological alteration(s) driving these behavioural modifications is only partially understood, which makes it difficult to draw more than a correlation between T. gondii infection and changes in brain homeostasis. Moreover, it is barely known which among the brain regions governing fear and stress responses are preferentially affected during T. gondii infection. Studies aiming at an in-depth dissection of underlying molecular mechanisms occurring at the host and parasite levels will be discussed in this review. Addressing this reminiscent topic in the light of recent technical progress and new discoveries regarding fear response, olfaction and neuromodulator mechanisms could contribute to a better understanding of this complex host–parasite interaction.

scholarly journals Reappearance of Hippocampal CA1 Neurons after Ischemia is Associated with Recovery of Learning and Memory

2005 ◽  
Vol 25 (12) ◽  
pp. 1586-1595 ◽  
Author(s):  
Olof Bendel ◽  
Tjerk Bueters ◽  
Mia von Euler ◽  
Sven Ove Ögren ◽  
Johan Sandin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Functions ◽  
Spatial Learning And Memory ◽  
Neuronal Marker ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 ◽  
The Brain

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

scholarly journals Synergistic Effect of Docetaxel Plus Saponin Fraction of Vitex doniana on Prostate Specific Antigen and p53 in Nitrsobis (2-oxopropyl) Amine-induced Prostate Toxicity

2021 ◽  
pp. 17-22
Author(s):  
Ifeanacho Ezeteonu Abireh ◽  
Godson Emeka Anyanwu
Keyword(s):  
Synergistic Effect ◽  
Prostate Specific Antigen ◽  
Wistar Rats ◽  
Specific Antigen ◽  
P53 Expression ◽  
Male Wistar Rats ◽  
Saponin Fraction ◽  
Vitex Doniana ◽  
Dose Dependent ◽  
Group 1

Aim: This study investigated the synergistic effect of docetaxel plus saponin fraction of Vitex doniana on prostate specific antigen and p53 in nitrsobis (2-oxopropyl) amine-induced prostate toxicity in Wistar rat. Methodology: Twenty-four (24) male Wistar rats with elevated serum prostate specific antigen level were selected from a group of sixty (60) rats pretreated with subcutaneous Nitrosobis (2-oxopropyl) amine 5 mg/kg daily for 4 weeks. The selected 24 male Wistar rats were then grouped into 6 groups of four (4) rats each. Group 1 was given 1ml normal saline daily from day 1-28. Groups 2, 3, 4, 5, and 6 further received subcutaneous nitrosobis (2-oxopropyl) amine 5 mg/kg daily from day 1-28. In addition, groups 3, 4, 5, and 6 were given weekly intravenous docetaxel 8 mg/kg on day 15 and 22. In addition to docetaxel, groups 4, 5, and 6 were further treated with oral saponin at 250 mg/kg, 500 mg/kg, and 750 mg/kg, respectively, daily, from day 15-28. Immunoenzymometric assay method was used for analysis of blood sample for prostate specific antigen. The prostate tissues were subjected to immuno study using the ImmunoCruz Staining System (Lab Vision Corporation, Fremont, CA, USA). The quantitative evaluation of p53 was done by calculating the percentages of p53-immunostained nuclei (labeling index). Results: Significant increase in prostate specific antigen and p53 expression were observed in group 2 (treated with Nitrsobis (2-oxopropyl) amine alone) when compared with group 1 (control). Dose dependent decrease in prostate specific antigen and p53 expression were observed in groups 4, 5, and 6, treated with docetaxel 8 mg/kg plus 250 mg/kg, 500 mg/kg, and 750 mg/kg of saponin respectively. Conclusion: Docetaxel plus Saponin fraction of Vitex doniana significantly reduced the serum prostate specific antigen concentration and p53 expression in a dose dependent manner, with the group treated with 750 mg/kg showing the highest decrease in the parameters tested.

Hippocampus Retains the Periodicity of Gamma Stimulation In Vivo

2002 ◽  
Vol 88 (5) ◽  
pp. 2349-2354 ◽  
Author(s):  
J. E. Mikkonen ◽  
T. Grönfors ◽  
J. J. Chrobak ◽  
M. Penttonen
Keyword(s):  
Information Acquisition ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Short Term ◽  
Ca1 Pyramidal Cells ◽  
State Dependent ◽  
Hippocampal Ca1 ◽  
Oscillatory Rhythms ◽  
The Brain

Several behavioral state dependent oscillatory rhythms have been identified in the brain. Of these neuronal rhythms, gamma (20–70 Hz) oscillations are prominent in the activated brain and are associated with various behavioral functions ranging from sensory binding to memory. Hippocampal gamma oscillations represent a widely studied band of frequencies co-occurring with information acquisition. However, induction of specific gamma frequencies within the hippocampal neuronal network has not been satisfactorily established. Using both in vivo intracellular and extracellular recordings from anesthetized rats, we show that hippocampal CA1 pyramidal cells can discharge at frequencies determined by the preceding gamma stimulation, provided that the gamma is introduced in theta cycles, as occurs in vivo. The dynamic short-term alterations in the oscillatory discharge described in this paper may serve as a coding mechanism in cortical neuronal networks.

Mineralocorticoid Receptors and Glucocorticoid Receptors in HPA Stress Responses During Coping and Adaptation

2020 ◽  
Author(s):  
Edo Ronald de Kloet ◽  
Marian Joëls
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Coping Style ◽  
Glucocorticoid Receptors ◽  
Memory Storage ◽  
Salt Appetite ◽  
Mineralocorticoid Receptors ◽  
Stress Response System ◽  
Appraisal Processes ◽  
The Brain

The glucocorticoid hormones cortisol and corticosterone coordinate circadian events and are master regulators of the stress response. These actions of the glucocorticoids are mediated by mineralocorticoid receptors (NR3C2, or MRs) and glucocorticoid receptors (NR3C1, or GRs). MRs bind the natural glucocorticoids cortisol and corticosterone with a 10-fold higher affinity than GRs. The glucocorticoids are inactivated only in the nucleus tractus solitarii (NTS), rendering the NTS-localized MRs aldosterone-selective and involved in regulation of salt appetite. Everywhere else in the brain MRs are glucocorticoid-preferring. MR and GR are transcription factors involved in gene regulation but recently were also found to mediate rapid non-genomic actions. Genomic MRs, with a predominant localization in limbic circuits, are important for the threshold and sensitivity of the stress response system. Non-genomic MRs promote appraisal processes, memory retrieval, and selection of coping style. Activation of GRs makes energy substrates available and dampens initial defense reactions. In the brain, GR activation enhances appetitive- and fear-motivated behavior and promotes memory storage of the selected coping style in preparation of the future. Thus, MRs and GRs complement each other in glucocorticoid control of the initiation and termination of the stress response, suggesting that the balance in MR- and GR-mediated actions is crucial for homeostasis and health.

scholarly journals Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1722 ◽  
Author(s):  
Mark B. Plotnikov ◽  
Galina A. Chernysheva ◽  
Oleg I. Aliev ◽  
Vera I. Smol’iakova ◽  
Tatiana I. Fomina ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cerebral Ischemia ◽  
Endothelial Dysfunction ◽  
Neurological Deficit ◽  
Neuroprotective Effect ◽  
Global Cerebral Ischemia ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area ◽  
The Brain

c-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5′-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage. In rats with IQ-1S administration, the LCBF was significantly higher (by 60%) compared with that in the GCI control. Treatment with IQ-1S also decreases blood viscosity and endothelial dysfunction. A concentration-dependent decrease (IC50 = 0.8 ± 0.3 μM) of tone in isolated carotid arterial rings constricted with phenylephrine was observed after IQ-1S application in vitro. We also found that IQ-1S decreased the intensity of the lipid peroxidation in the brain tissue in rats with GCI. 2.2-Diphenyl-1-picrylhydrazyl scavenging for IQ-1S in acetonitrile and acetone exceeded the corresponding values for ionol, a known antioxidant. Overall, these results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant/antiradical IQ-1S activity.

scholarly journals Walnut Oil Prevents Scopolamine-Induced Memory Dysfunction in a Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1630
Author(s):  
Jianqiao Liao ◽  
Yifan Nai ◽  
Li Feng ◽  
Yimeng Chen ◽  
Mei Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Memory Impairment ◽  
Acetylcholinesterase Activity ◽  
Walnut Oil ◽  
Histological Changes ◽  
Hippocampal Ca1 ◽  
Malondialdehyde Content ◽  
Wet Weight ◽  
The Brain ◽  
Total Superoxide Dismutase

For thousands of years, it has been widely believed that walnut is a kind of nut that has benefits for the human body. Walnut oil, accounting for about 70% of walnut, mainly consists of polyunsaturated fatty acids. To investigate the effect of walnut oil on memory impairment in mice, scopolamine (3 mg/kg body weight/d) was used to establish the animal model during Morris Water Maze (MWM) tests. Walnut oil was administrated orally at 10 mL/kg body weight/d for 8 consecutive weeks. The results showed that walnut oil treatment ameliorated the behavior of the memory-impaired mice in the MWM test. Additionally, walnut oil obviously inhibited acetylcholinesterase activity (1.26 ± 0.12 U/mg prot) (p = 0.013) and increased choline acetyltransferase activity (129.75 ± 6.76 U/mg tissue wet weight) in the brains of scopolamine-treated mice (p = 0.024), suggesting that walnut oil could prevent cholinergic function damage in mice brains. Furthermore, walnut oil remarkably prevented the decrease in total superoxide dismutase activity (93.30 ± 5.50 U/mg prot) (p = 0.006) and glutathione content (110.45 ± 17.70 mg/g prot) (p = 0.047) and the increase of malondialdehyde content (13.79 ± 0.96 nmol/mg prot) (p = 0.001) in the brain of scopolamine-treated mice, indicating that walnut oil could inhibit oxidative stress in the brain of mice. Furthermore, walnut oil prevented histological changes of neurons in hippocampal CA1 and CA3 regions induced by scopolamine. These findings indicate that walnut oil could prevent memory impairment in mice, which might be a potential way for the prevention of memory dysfunctions.

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