High Levels of SIRT1 Expression as a Protective Mechanism Against Disease-Related Conditions

SIRT1 protein, a member of Silent Information Regulator 2 (Sir2) protein family, have gained considerable attention as epigenetic regulators for a great area in the human physiology. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, cardiovascular diseases, cancer and neurodegeneration. Here, we provide an overview of the association of the increasing level of SIRT1 protein for regulating some disease related conditions such as obesity, cardiovascular diseases and neurodegeneration. This review also provides a detailed molecular understanding of the interaction of the some basic molecules with increasing SIRT1 levels rather than reduction of the SIRT1 expression. In this context, the current approaches to enhancing the expression of SIRT1 points the importance of epigenetics in several age-related diseases to provide a healthy aging by developing novel therapies which can prevent or damp the progression of some diseases

Kaempferol treatment ameliorates memory impairments in STZ-induced neurodegeneration by acting on reelin signaling

Many treatment initiatives, like herbal products and their active ingredients, aim to alleviate neurodegeneration to increase cognitive functions. Kaempferol may be a candidate molecule for treating neurodegeneration because of its antioxidant effects. In the present study, we examined the molecular changes associated with kaempferol’s memory-enhancing effects on streptozotocin (STZ)-induced neurodegeneration. After intracerebroventricular STZ injection in Long-Evans male rats, intraperitoneal kaempferol was administered for 12 days. The Morris water maze (MWM) was used to measure learning and memory performance in the rats, and proteins related to memory formation were investigated in the hippocampi with western blotting. Kaempferol improved learning performance and memory decline in STZ-treated rats. At the molecular level, STZ-induced neurodegeneration resulted in a decrease in the expression of GAD67, reelin, and phosphorylated-NMDAR. However, kaempferol treatment ameliorated these changes by enhancing their levels similar to the controls. While neither STZ injection nor kaempferol treatment produced any significant change in phosphorylated-CAMKII levels, they increased the expression of klotho and prealbumin. These results show that kaempferol has positive effects on memory loss, affecting synaptic plasticity by ameliorating both the levels and activity of memory-relevant molecules through reelin signaling. In summary, this study provides a guide to future studies by examining in detail the healing effect of kaempferol as a candidate molecule in the treatment of neurodegeneration, such as that observed in Alzheimer’s disease

Prenatal ethanol intoxication and maternal intubation stress alter cell survival and apoptosis in the postnatal development of rat hippocampus

It is well known that the fetal ethanol exposure and prenatal stress may have adverse effects on brain development. Interestingly, some morphological and functional recovery from their teratogenic effects that take place during brain maturation. However, mechanisms that underlie this recovery are not fully elucidated. The aim of this study was to examine whether the postnatal attenuation of fetal alcohol - and maternal stress-induced morphological and functional deficits correlates with compensatory changes in the expression/activation of the brain proteins involved in inflammation, cell survival and apoptosis. In this project, we investigated the hippocampus which belongs to the brain regions most susceptible to the adverse effects of prenatal ethanol exposure. Pregnant rat dams were administered ethanol (A) or isocaloric glucose solution (IC) by a gastric intubation during gestational days 7-20. The pure control group received ad libitum laboratory chow and water with no other treatment. The hippocampi of fetal-ethanol and control pups were examined at the postnatal day (PD)1, PD10, PD30 and PD60. Moderate fetal-ethanol exposure and prenatal intubation stress caused a significant increase in molecular factors relating to inflammation (iNOS) and cell survival/apoptosis pathways (PTEN, GSK-3 and ERK) at birth, with a rapid compensation from these developmental deficits upon removal of alcohol at PD10. Indeed, an increase in ERK1/2 and JNK1/2 activation at PD30 was observed with ethanol consumption. It indicates that the recovery process in A and IC brains started soon after the birth upon the ethanol and stressor withdrawal and continued until the adulthood

Angiotensin IV improves spatial memory in streptozotocin-induced diabetic rats by reducing oxidative stress and altering BDNF levels

In this study, we investigated the protective effects of angiotensin IV (Mg IV) on cognitive function in streptozotocin (STZ)-induced diabetic rats. Male Wistar albino rats, were randomly divided into four groups; control (C), diabetes (Dia, 60 mg/kg, STZ, i.p.), Mg IV (5 mu g/kg, s.c.) and Dia+Ang W. The passive avoidance and Morris water maze (MWM) tests were used to evaluate learning and memory performance. Behavioral tests were carried out between 21 and 30 days after the initial Ang IV injection. Hippocampi were dissected and retained for biochemical and Western blot analysis. The Dia group exhibited the poorest behavioral results, while the Dia+Ang W group performed highest on the MWM task. Superoxide dismutase, glutathione peroxidase, and malondialdehyde levels increased significantly in the Dia group compared to Dia+Ang IV. Brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate levels were significantly elevated, while levels of GABA(A) significantly decreased, in the Dia+Ang IV group compared to the Dia group. These findings suggest that peripheral administration of Ang IV ameliorated spatial memory in diabetic rats by decreasing hippocampal oxidative stress and BDNF levels

Hepatoprotective actions of melatonin by mainly modulating oxidative status and apoptosis rate in lipopolysaccharide-induced liver damage

Aim: One of the serious complications of sepsis is liver damage and liver failure. This study aimed to evaluate the protective and therapeutic potential of melatonin in rats with lipopolysaccharide-induced sepsis. Main methods: Female Spraque–Dawley rats received single a dose of 7.5 mg/kg lipopolysaccharide in saline to create a 24-h sepsis model. One of the other groups received melatonin at a dose of 10 mg/kg/day beginning 1 week before sepsis induction to the end of the experiment. The melatonin group received the same doses of melatonin for the same duration but not lipopolysaccharide. The vehicle group received the same doses of saline, the vehicle of melatonin, for the same duration. Twenty-four hours after the last injection, the rats were decapitated. By appropriate histochemical, immunohistochemical, biochemical, and molecular techniques, anti-necrotic, anti-apoptotic, anti-necroptotic, anti-inflammatory, and antioxidant effects of melatonin were assessed. Key findings: Lipopolysaccharide has disrupted liver functions by inducing oxidative stress, inflammation, necrotic, apoptotic, and necroptotic cell death, thus disrupting liver functions. Melatonin was found to be beneficial in terms of inhibiting the intrinsic pathway of apoptosis and tissue oxidant levels, stimulating tissue antioxidant enzyme levels, and restoring hepatocyte functions. Significance: Melatonin, at those doses and duration, was found to be hepatoprotective by mainly modulating oxidative status and apoptosis rate, however, failed to significantly reduce histopathological damage. We suggest that longer-term melatonin administration may produce anti-inflammatory and anti-necrotic effects as well. © 2023 Informa UK Limited, trading as Taylor & Francis Group

Genç erişkin Wistar sıçanlarda etanol alımının hafıza üzerindeki etkisinin ve hipokampüste oluşan moleküler değişikliklerin incelenmesi.

The aim of the present study was to examine retention of spatial reference memory after 6 (Experiment I) and 15days (Experiment II) of binge-like drinking and during alcohol withdrawal in young adult Wistar rats. Prior to alcohol treatment, rats received Morris Water Maze (MWM) training. Afterwards, rats were intragastrically administered ethanol at the dose increasing from 4.5g-to-12g/kg. Intubation control groups (n=7 and n=10, respectively) received infusions of a sucrose solution without ethanol. Subsequently, all subjects were given a single probe trial in the MWM to test memory retention. In both experiments, there were three alcohol groups: A0 group (n=7) tested 4h after the last alcohol administration for acute effects of ethanol; A24 group (n=7) tested 24h after alcohol cessation, when acute ethanol effects disappear but withdrawal symptoms does not develop yet; A72 group (n=7) tested 72h after the last ethanol infusion for withdrawal effects. Finally, potential molecular changes in hippocampus were examined using Fourier Transform Infra-Red (FT-IR) spectroscopy. The blood alcohol concentration was 605.67±36mg/dl. In Experiment I, due to the low overall level of performance in the memory retention task the behavioral effects of ethanol could not be evaluated and no significant betweengroup differences were observed in Experiment II. In Experiment I, no significant changes in the molecular make-up of the hippocampus were noted. Conversely, in Experiment II, significant changes in protein, lipid, and nucleic acid profiles related to ethanol intake and withdrawal were found. They are linked to both development of tolerance to ethanol and adverse withdrawal effects.M.S. - Master of Scienc

Normal ve fötal dönemde alkole maruz kalmış sıçanlarda doğumdan sonraki ilk iki ayda hippokampus gelişiminin araştırılması.

Behavioral deficits caused by fetal-alcohol are well expressed in juvenile subjects but usually ameliorate with maturation. It suggests some kind of postnatal regeneration. The aim of the present study was to examine the potential correlation between behavioral recovery and the postnatal hippocampal development in the fetal-alcohol rats. This study included behavioral tests applied to juvenile and adult subjects, unbiased stereology to investigate changes in neuron numbers and hippocampal volumes, the postnatal tracing and analysis of the hippocampal principal neuron’s morphology, investigation of age-dependent changes in the distribution of doublecortin-expressing neurons, and evaluation of synaptic development by assessing age-dependent changes in the regional immunoreactivity/expression of synaptophysin and PSD95. Rats have been exposed to ethanol throughout 7-21 gestation days with daily ethanol dose of 6g/kg delivered by intragastric intubation to the pregnant dams. The morphological characteristics were examined on postnatal days P1, P10, P30, P60, in hippocampal CA1, CA3, and DG subregions, in fetal-alcohol and control rats. Both, stereological and doublecortin-immunoreactivity data pointed towards a possibility of limited neurogenesis taking place during a protracted postnatal period not only in the germinal zones (SGZ and SVZ) but also in the hippocampal CA regions. Ethanol effect on postnatal hippocampal development was limited to marginally lower number of granular cells in DG on P30. It correlated with poorer cognitive performance in the fetal-alcohol group. The treatment effect on the morphology of hippocampal neurons was observed mainly in CA region at P1 and seemed to be attributed more to the intubation stress than the ethanol itself.Ph.D. - Doctoral Progra

Prenatal exposure of diclofenac sodium alters the behavioral development of young Wistar rats

Diclofenac sodium (DS), a potent inhibitor of cyclooxygenase, reduces the release of arachidonic acid and formation of prostaglandins. Being a nonsteroid drug that shows antiinflammatory action, the possible side effects of fetal DS administration gain importance in public and medical applications. Herein, the effects of DS administration (1 mg/kg) during gestational days 5-20 were investigated on the performance of Wistar rat pups in a variety of behavioral tasks. Four-week-old pups were subjected to sensory motor tests, a plus maze, an open field, the Morris water maze, and a radial arm maze. Fetal DS disrupted some sensory motor performances, such as visual placing and climbing in both females and males. In the open field, DS females had a higher level of anxiety and male DS pups habituated to the environment slowly compared to controls. The DS pups showed slower rates of learning, whereas no substantial between-group differences were found in the performance of spatial memory compared to both controls. Furthermore, working memory was negatively affected by fetal DS. In conclusion, it was indicated that DS administration during pregnancy had slight behavioral impacts with a delay in learning and a defect in the short-term memory in juvenile rats

The interaction of SIRT1, TLR4 and IL7 in human dementia

3rd International Congress of the Turkish-Neuroendocrinology-Society -- JUN 29-JUL 01, 2018 -- Malatya, TURKEYWOS: 000445952400081…Turkish Neuroendocrinol Societ