scholarly journals Effects of Long-Term Treatment with a Blend of Highly Purified Olive Secoiridoids on Cognition and Brain ATP Levels in Aged NMRI Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Martina Reutzel ◽  
Rekha Grewal ◽  
Carmina Silaidos ◽  
Jens Zotzel ◽  
Stefan Marx ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Citrate Synthase ◽  
Brain Aging ◽  
Mrna Levels ◽  
Nmri Mice ◽  
Aged Mice ◽  
Atp Levels ◽  
Long Term Treatment ◽  
The Brain

Aging represents a major risk factor for developing neurodegenerative diseases such as Alzheimer’s disease (AD). As components of the Mediterranean diet, olive polyphenols may play a crucial role in the prevention of AD. Since mitochondrial dysfunction acts as a final pathway in both brain aging and AD, respectively, the effects of a mixture of highly purified olive secoiridoids were tested on cognition and ATP levels in a commonly used mouse model for brain aging. Over 6 months, female NMRI mice (12 months of age) were fed with a blend containing highly purified olive secoiridoids (POS) including oleuropein, hydroxytyrosol and oleurosid standardized for 50 mg oleuropein/kg diet (equivalent to 13.75 mg POS/kg b.w.) or the study diet without POS as control. Mice aged 3 months served as young controls. Behavioral tests showed deficits in cognition in aged mice. Levels of ATP and mRNA levels of NADH-reductase, cytochrome-c-oxidase, and citrate synthase were significantly reduced in the brains of aged mice indicating mitochondrial dysfunction. Moreover, gene expression of Sirt1, CREB, Gap43, and GPx-1 was significantly reduced in the brain tissue of aged mice. POS-fed mice showed improved spatial working memory. Furthermore, POS restored brain ATP levels in aged mice which were significantly increased. Our results show that a diet rich in purified olive polyphenols has positive long-term effects on cognition and energy metabolism in the brain of aged mice.

scholarly journals Cerebral Mitochondrial Function and Cognitive Performance during Aging: A Longitudinal Study in NMRI Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Martina Reutzel ◽  
Rekha Grewal ◽  
Benjamin Dilberger ◽  
Carmina Silaidos ◽  
Aljoscha Joppe ◽  
...  
Keyword(s):  
Longitudinal Data ◽  
Cognitive Performance ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Aging Process ◽  
Brain Aging ◽  
Model Organisms ◽  
Nmri Mice ◽  
Aged Mice ◽  
The Brain

Brain aging is one of the major risk factors for the development of several neurodegenerative diseases. Therefore, mitochondrial dysfunction plays an important role in processes of both, brain aging and neurodegeneration. Aged mice including NMRI mice are established model organisms to study physiological and molecular mechanisms of brain aging. However, longitudinal data evaluated in one cohort are rare but are important to understand the aging process of the brain throughout life, especially since pathological changes early in life might pave the way to neurodegeneration in advanced age. To assess the longitudinal course of brain aging, we used a cohort of female NMRI mice and measured brain mitochondrial function, cognitive performance, and molecular markers every 6 months until mice reached the age of 24 months. Furthermore, we measured citrate synthase activity and respiration of isolated brain mitochondria. Mice at the age of three months served as young controls. At six months of age, mitochondria-related genes (complex IV, creb-1, β-AMPK, and Tfam) were significantly elevated. Brain ATP levels were significantly reduced at an age of 18 months while mitochondria respiration was already reduced in middle-aged mice which is in accordance with the monitored impairments in cognitive tests. mRNA expression of genes involved in mitochondrial biogenesis (cAMP response element-binding protein 1 (creb-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), nuclear respiratory factor-1 (Nrf-1), mitochondrial transcription factor A (Tfam), growth-associated protein 43 (GAP43), and synaptophysin 1 (SYP1)) and the antioxidative defense system (catalase (Cat) and superoxide dismutase 2 (SOD2)) was measured and showed significantly decreased expression patterns in the brain starting at an age of 18 months. BDNF expression reached, a maximum after 6 months. On the basis of longitudinal data, our results demonstrate a close connection between the age-related decline of cognitive performance, energy metabolism, and mitochondrial biogenesis during the physiological brain aging process.

scholarly journals Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Magdalena Cristóbal-García ◽  
Fernando E. García-Arroyo ◽  
Edilia Tapia ◽  
Horacio Osorio ◽  
Abraham S. Arellano-Buendía ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Renal Cortex ◽  
Systemic Hypertension ◽  
Tubular Damage ◽  
Short Term ◽  
Mitochondrial Alterations ◽  
Atp Levels ◽  
Long Term Treatment

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

scholarly journals Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Anke Schloesser ◽  
Tuba Esatbeyoglu ◽  
Stefanie Piegholdt ◽  
Janina Dose ◽  
Naoko Ikuta ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Cyclodextrin Complex ◽  
Aged Mice ◽  
Atp Levels ◽  
The Brain

Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, includingγ- andδ-tocotrienol (T3), may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase,γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice.

scholarly journals Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 176 ◽  
Author(s):  
Sung Nam ◽  
Misun Seo ◽  
Jin-Seok Seo ◽  
Hyewhon Rhim ◽  
Sang-Soep Nahm ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Cellular Proliferation ◽  
Brain Aging ◽  
Memory Function ◽  
Interleukin 1 ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Normal Brain ◽  
Long Term Treatment

Ascorbic acid is essential for normal brain development and homeostasis. However, the effect of ascorbic acid on adult brain aging has not been determined. Long-term treatment with high levels of D-galactose (D-gal) induces brain aging by accumulated oxidative stress. In the present study, mice were subcutaneously administered with D-gal (150 mg/kg/day) for 10 weeks; from the seventh week, ascorbic acid (150 mg/kg/day) was orally co-administered for four weeks. Although D-gal administration alone reduced hippocampal neurogenesis and cognitive functions, co-treatment of ascorbic acid with D-gal effectively prevented D-gal-induced reduced hippocampal neurogenesis through improved cellular proliferation, neuronal differentiation, and neuronal maturation. Long-term D-gal treatment also reduced expression levels of synaptic plasticity-related markers, i.e., synaptophysin and phosphorylated Ca2+/calmodulin-dependent protein kinase II, while ascorbic acid prevented the reduction in the hippocampus. Furthermore, ascorbic acid ameliorated D-gal-induced downregulation of superoxide dismutase 1 and 2, sirtuin1, caveolin-1, and brain-derived neurotrophic factor and upregulation of interleukin 1 beta and tumor necrosis factor alpha in the hippocampus. Ascorbic acid-mediated hippocampal restoration from D-gal-induced impairment was associated with an enhanced hippocampus-dependent memory function. Therefore, ascorbic acid ameliorates D-gal-induced impairments through anti-oxidative and anti-inflammatory effects, and it could be an effective dietary supplement against adult brain aging.

scholarly journals A Walnut-enriched Diet and Physical Activity Enhanced Cognitive and Motor Function in Aged Mice (P14-010-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Carsten Esselun ◽  
Benjamin Dilberger ◽  
Carmina Silaidos ◽  
Gunter Eckert
Keyword(s):  
Physical Activity ◽  
Spatial Memory ◽  
Motor Function ◽  
Mitochondrial Function ◽  
Brain Aging ◽  
Enriched Environment ◽  
Motor Functions ◽  
Nmri Mice ◽  
Aged Mice ◽  
Y Maze

Abstract Objectives This study aims to investigate walnut's effect alone and in combination with an enriched environment on brain aging of aged NMRI mice by investigation of cognition and motor functions. Furthermore, it aims to identify the underlying mechanisms by evaluating the expression of relevant genes. Methods NMRI mice (12mo.) were fed with a 6% walnut-enriched diet (WED) or control diet respectively, for the duration of 6 months. Additionally, one WED group was exposed to an enriched environment. Cognition and motor functions were assessed to evaluate walnut's effect on spatial memory, general physical activity and motor coordination. Conducted tests included Y-Maze alternation, open field and rotarod. Expression levels of relevant genes including synaptophysin, NGF and BDNF were measured via qPCR in brain tissue. Mitochondrial function was investigated by testing for ATP levels and mitochondrial membrane potential in dissociated brain cells and oxygen consumption of the oxidative phosphorylation system of freshly isolated mitochondria. Results Intake of the walnut diet significantly increased the alternation rate in a Y-Maze experiment (P < 0.05). Physical activity did not further improve this effect on spatial memory of mice, but increased mice’ activity (P < 0.001) in general. Motor function in rotarod test was not improved by walnut intake alone, but significantly increased by added enrichment (P < 0.01). Gene expression of synaptophysin was significantly increased for walnuts alone (P < 0.05), while BDNF and NGF expression appeared to be unaffected. Additional enriched environment resulted in a trend for these genes to be increased as well. Results imply that mitochondrial function is not linked to these improvements. Conclusions Long term walnut diet significantly improved cognitive function in aged mice. Physical activity additionally improved motor functions. These benefits could possibly be explained by increased expression of genes involved in neuronal plasticity. Funding Sources Grant from California Walnut Commission.

scholarly journals Platelet counts in epileptic children receiving valproic acid

2020 ◽  
Vol 60 (1) ◽  
pp. 13-7
Author(s):  
Lilik Indrayati ◽  
Fadhilah Tia Nur ◽  
Bambang Soebagyo
Keyword(s):  
Valproic Acid ◽  
Epileptic Seizures ◽  
Term Treatment ◽  
Common Adverse Event ◽  
Platelet Counts ◽  
Central Java ◽  
Long Term Treatment ◽  
Epileptic Children ◽  
The Brain

Background Epileptic seizures are a transient occurrence resulting from abnormal, excessive, or synchronous neural activity in the brain. Epilepsy requires long-term treatment, increasingly larger doses, and combination therapy. Anti-epileptic drugs (AEDs), especially valproic acid (VPA), are the main treatment of choice. Thrombocytopenia is the most common adverse event from AEDs. Objective To evaluate platelet counts in epileptic children receiving valproic acid monotherapy vs. polytherapy. Methods This analytic, observational, retrospective cohort study was conducted in children with epilepsy below 18 years of age and treated in Dr. Moewardi Hospital, Surakarta, Central Java. Subjects had received VPA treatment for at least 6 months, either as monotherapy or polytherapy. There were 40 subjects in each group (VPA monotherapy vs. VPA polytherapy). The exclusion criteria were patients who had thrombocytopenia and did not take valproic acid regularly. The data was taken from laboratory and the outcome assessed was decreasing of platelet count. Results  Administration of VPA as monotherapy vs. polytherapy was not significantly associated with incidence of thrombocytopenia. However, duration of VPA use > 2 years was associated with significantly greater proportion of thrombocytopenia, with OR 33.0 (95%CI 4.157 to 261.962; P=0.001) compared to VPA use < 2 years. Similarly, VPA dose of >30 mg/kg/day was significantly associated with greater proportion of thrombocytopenia, with OR 4.081 (95%CI 1.337 to 12.458; P=0.013) compared to <30 mg/kg/day dosage. Conclusion Incidence of thrombocytopenia is not significantly different between VPA as a  monotherapy and polytherapy. However, higher VPA dose and longer VPA duration are associated with higher proportion of thrombocytopenia.

scholarly journals Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

2015 ◽  
Vol 28 (2) ◽  
pp. 110-116
Author(s):  
Artur Palasz ◽  
Ewa Rojczyk ◽  
Milosz Golyszny ◽  
Lukasz Filipczyk ◽  
John J. Worthington ◽  
...  
Keyword(s):  
Brain Structures ◽  
Term Treatment ◽  
Complex Nature ◽  
Mrna Levels ◽  
Neuropeptide S ◽  
Long Term Treatment ◽  
Rat Brainstem ◽  
Haloperidol Treatment ◽  
Potential Interactions

ObjectiveThe brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression.MethodsWe assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction.ResultsChronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum.ConclusionsThis stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

scholarly journals Regulation of pituitary inhibin/activin subunits and follistatin gene expression by GnRH in female rats

2011 ◽  
Vol 210 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Petra Popovics ◽  
Zoltan Rekasi ◽  
Alan J Stewart ◽  
Magdolna Kovacs
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Inhibin B ◽  
Female Rats ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Short Term ◽  
Α Subunit ◽  
Long Term Treatment

Pituitary inhibin B, activin B, and follistatin are local regulators of FSH. Activin B is a homodimeric molecule (βB–βB), while inhibin B contains an α and a βB subunit. The regulation of gene expression of α, βB, and follistatin by local and endocrine hormones was examined in pituitaries from female rats and in perifused pituitary cells by RT-PCR. Ovariectomy (OVX) induced an elevation in the mRNA level of α and βB subunits and follistatin. Short-term (4 h) treatment of pituitary cells with GnRH decreased both the inhibin α and the inhibin/activin βB subunit mRNA levels, while long-term treatment (20 h) with 100 nM GnRH stimulated the expression of both subunits. In contrast, the mRNA level of follistatin was elevated after the short-term GnRH treatment. Long-term exposure of pituitary cells to estradiol and inhibin B suppressed the mRNA expression of βB and had no effect on the expression of α subunit and follistatin. Our results demonstrate that the increased expressions of inhibin/activin subunits and follistatin in the post-OVX period can be induced by the lack of gonadal negative feedback, resulting in a high GnRH environment in the pituitary. This study reports for the first time that GnRH administered in high doses and for a long period stimulates the gene expression of inhibin/activin subunits and thereby may contribute to the stimulatory effect of OVX on the expression of these genes.

Long-term treatment with clonidine and α-receptors in the brain of Normotensive rats

1984 ◽  
Vol 321 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Franca Cerrito ◽  
Maria Martire ◽  
Paolo Preziosi
Keyword(s):  
Term Treatment ◽  
Long Term Treatment ◽  
The Brain
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