scholarly journals Sexually Dimorphic Effects of a Western Diet on Brain Mitochondrial Bioenergetics and Neurocognitive Function

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4222
Author(s):  
Magen N. Lord ◽  
Jun-Won Heo ◽  
Albino G. Schifino ◽  
Jessica R. Hoffman ◽  
Kristen N. Donohue ◽  
...  

A Western diet (WD), high in sugars and saturated fats, impairs learning and memory function and contributes to weight gain. Mitochondria in the brain provide energy for neurocognitive function and may play a role in body weight regulation. We sought to determine whether a WD alters behavior and metabolic outcomes in male and female rodents through impacting hippocampal and hypothalamic mitochondrial bioenergetics. Results revealed a sexually dimorphic macronutrient preference, where males on the WD consumed a greater percentage of calories from fat/protein and females consumed a greater percentage of calories from a sugar-sweetened beverage. Both males and females on a WD gained body fat and showed impaired glucose tolerance when compared to same-sex controls. Males on a WD demonstrated impaired hippocampal functioning and an elevated tendency toward a high membrane potential in hippocampal mitochondria. Comprehensive bioenergetics analysis of WD effects in the hypothalamus revealed a tissue-specific adaption, where males on the WD oxidized more fat, and females oxidized more fat and carbohydrates at peak energy demand compared to same-sex controls. These results suggest that adult male rats show a susceptibility toward hippocampal dysfunction on a WD, and that hypothalamic mitochondrial bioenergetics are altered by WD in a sex-specific manner.

2015 ◽  
Vol 283 ◽  
pp. 69-77 ◽  
Author(s):  
Rodrigo Triana-Del Rio ◽  
Miriam B. Tecamachaltzi-Silvarán ◽  
Victor X. Díaz-Estrada ◽  
Deissy Herrera-Covarrubias ◽  
Aleph A. Corona-Morales ◽  
...  

2020 ◽  
Vol 15 ◽  
Author(s):  
Samar R. Saleh ◽  
Mariam M. Abady ◽  
Mohammed Nofal ◽  
Nashwa W. Yassa ◽  
Mohamed S. Abdel-latif ◽  
...  

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.


Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 422
Author(s):  
Zhanat Koshenov ◽  
Furkan E. Oflaz ◽  
Martin Hirtl ◽  
Johannes Pilic ◽  
Olaf A. Bachkoenig ◽  
...  

The endoplasmic reticulum (ER) is a complex, multifunctional organelle of eukaryotic cells and responsible for the trafficking and processing of nearly 30% of all human proteins. Any disturbance to these processes can cause ER stress, which initiates an adaptive mechanism called unfolded protein response (UPR) to restore ER functions and homeostasis. Mitochondrial ATP production is necessary to meet the high energy demand of the UPR, while the molecular mechanisms of ER to mitochondria crosstalk under such stress conditions remain mainly enigmatic. Thus, better understanding the regulation of mitochondrial bioenergetics during ER stress is essential to combat many pathologies involving ER stress, the UPR, and mitochondria. This article investigates the role of Sigma-1 Receptor (S1R), an ER chaperone, has in enhancing mitochondrial bioenergetics during early ER stress using human neuroblastoma cell lines. Our results show that inducing ER stress with tunicamycin, a known ER stressor, greatly enhances mitochondrial bioenergetics in a time- and S1R-dependent manner. This is achieved by enhanced ER Ca2+ leak directed towards mitochondria by S1R during the early phase of ER stress. Our data point to the importance of S1R in promoting mitochondrial bioenergetics and maintaining balanced H2O2 metabolism during early ER stress.


2015 ◽  
Vol 40 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Aline Isabel da Silva ◽  
Glauber Ruda Feitoza Braz ◽  
Reginaldo Silva-Filho ◽  
Anderson Apolonio Pedroza ◽  
Diorginis Soares Ferreira ◽  
...  

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.


1999 ◽  
Vol 50 (3) ◽  
pp. 193-199 ◽  
Author(s):  
Reuben W Rhees ◽  
Hamid N Al-Saleh ◽  
Edward W Kinghorn ◽  
Donovan E Fleming ◽  
Edwin D Lephart

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zachary Ip ◽  
Gratianne Rabiller ◽  
Jiwei He ◽  
Shivalika Chavan ◽  
Yasuo Nishijima ◽  
...  

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.


2019 ◽  
Vol 149 (9) ◽  
pp. 1493-1502 ◽  
Author(s):  
Jenny L Gonzalez-Armenta ◽  
Zhengrong Gao ◽  
Susan E Appt ◽  
Mara Z Vitolins ◽  
Kristofer T Michalson ◽  
...  

ABSTRACT Background Western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas Mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. Previous work has included population-based studies with limited evidence for causation or animal studies focused on single macro- or micronutrients; therefore, primate animal models provide an opportunity to determine potential mechanisms underlying the effects of dietary patterns on health and disease. Objective The aim of this study was to determine the effects of whole dietary patterns, either a Western or Mediterranean diet, on skeletal muscle mitochondrial bioenergetics in cynomolgus macaques. Methods In this study, 22 adult female cynomolgus macaques (∼11–14 y by dentition) were fed either a Western or Mediterranean diet for 30 mo. The Western diet was designed to mimic the diet of a middle-aged American woman and the Mediterranean diet included key aspects of Mediterranean diets studied in humans, such as plant-based proteins and fat, complex carbohydrates, and fiber. Diets were matched on macronutrient composition (16% protein, 54% carbohydrate, and 31% fat) and cholesterol content. Skeletal muscle was collected for high-resolution respirometry, citrate synthase activity, and western blot measurements. Pearson correlation analysis between respirometry measures and measures of carbohydrate metabolism was also performed. Results We found that consumption of a Western diet resulted in significantly higher mitochondrial respiration with fatty acid oxidation (FAO) (53%), FAO + complex I (52%), complex I + II (31%), max electron transport system (ETS) (31%), and ETS rotenone sensitive (31%) than did consumption of a Mediterranean diet. In addition, measures of respiration in response to fatty acids were significantly and positively correlated with both insulin resistance and plasma insulin concentrations. Conclusions This study highlights the importance of dietary composition in mitochondrial bioenergetics and that diet can influence skeletal muscle mitochondrial respiration independently of other factors such as macronutrient composition.


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