scholarly journals Examination of BDNF Treatment on BACE1 Activity and Acute Exercise on Brain BDNF Signaling

2021 ◽  
Vol 15 ◽  
Author(s):  
Bradley J. Baranowski ◽  
Grant C. Hayward ◽  
Daniel M. Marko ◽  
Rebecca E. K. MacPherson
Keyword(s):  
Prefrontal Cortex ◽  
Direct Effect ◽  
High Fat Diet ◽  
Beta Amyloid ◽  
Treadmill Running ◽  
Pathological Feature ◽  
High Fat ◽  
Acute Bout ◽  
Exercise Induced ◽  
Bace1 Activity

Perturbations in metabolism results in the accumulation of beta-amyloid peptides, which is a pathological feature of Alzheimer’s disease. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate limiting enzyme responsible for beta-amyloid production. Obesogenic diets increase BACE1 while exercise reduces BACE1 activity, although the mechanisms are unknown. Brain-derived neurotropic factor (BDNF) is an exercise inducible neurotrophic factor, however, it is unknown if BDNF is related to the effects of exercise on BACE1. The purpose of this study was to determine the direct effect of BDNF on BACE1 activity and to examine neuronal pathways induced by exercise. C57BL/6J male mice were assigned to either a low (n = 36) or high fat diet (n = 36) for 10 weeks. To determine the direct effect of BDNF on BACE1, a subset of mice (low fat diet = 12 and high fat diet n = 12) were used for an explant experiment where the brain tissue was directly treated with BDNF (100 ng/ml) for 30 min. To examine neuronal pathways activated with exercise, mice remained sedentary (n = 12) or underwent an acute bout of treadmill running at 15 m/min with a 5% incline for 120 min (n = 12). The prefrontal cortex and hippocampus were collected 2-h post-exercise. Direct treatment with BDNF resulted in reductions in BACE1 activity in the prefrontal cortex (p < 0.05), but not the hippocampus. The high fat diet reduced BDNF content in the hippocampus; however, the acute bout of exercise increased BDNF in the prefrontal cortex (p < 0.05). These novel findings demonstrate the region specific differences in exercise induced BDNF in lean and obese mice and show that BDNF can reduce BACE1 activity, independent of other exercise-induced alterations. This work demonstrates a previously unknown link between BDNF and BACE1 regulation.

Ceramide and sphingomyelin levels are changed in prefrontal cortex and hippocampus of rats on high-fat diet

2013 ◽  
Vol 65 ◽  
pp. 34-35
Author(s):  
Halina Car ◽  
Anna Fiedorowicz ◽  
Sławomir Prokopiuk ◽  
Małgorzata Żendzian-Piotrowska
Keyword(s):  
Prefrontal Cortex ◽  
High Fat Diet ◽  
High Fat

P6285Protective effects of exercise on vascular function are mediated by NADPH oxidase 4

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Morawietz ◽  
H Langbein ◽  
A Shahid ◽  
A Hofmann ◽  
J Mittag ◽  
...  
Keyword(s):  
Physical Activity ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Intracellular Calcium ◽  
High Fat Diet ◽  
Calcium Release ◽  
Protective Effects ◽  
Wild Type ◽  
High Fat ◽  
Exercise Induced

Abstract Background/Introduction Physical activity is one of the most potent strategies to prevent endothelial dysfunction. Recent evidence indicates vaso-protective properties of H2O2 produced by main endothelial NADPH oxidase isoform 4 (Nox4) in the vasculature. Purpose Therefore, we hypothesized that Nox4 connects physical activity with vaso-protective effects. Methods and results Analysis of endothelial function by Mulvany myograph showed endothelial dysfunction in wild-type as well as in Nox4−/− mice after 20 weeks on high-fat diet. Access to voluntary running wheels during high-fat diet prevented endothelial dysfunction in wild-type but not in Nox4−/− mice. Mechanistically, exercise led to increased H2O2 release in the aorta of wild-type mice with increased phosphorylation of eNOS pathway member AKT serine/threonine kinase 1 (Akt1), subsequently. Both effects were diminished in aortas of Nox4−/− mice. Deletion of Nox4 also led to decreased capacity for intracellular calcium release and reduced phenylephrine-mediated contraction, whereas potassium-induced contraction was unaffected. H2O2 scavenger catalase reduced phenylephrine-contraction in wild-type mice. Supplementation of H2O2 increased phenylephrine-induced contraction in Nox4−/− mice. Exercise induced key regulator of mitochondria biogenesis peroxisome proliferative activated receptor gamma, coactivator 1 alpha (Ppargc1a) in wild-type but not Nox4−/− mice. Furthermore, exercise induced citrate synthase activity and reduced mitochondria mass in the absence of Nox4. Thus, Nox4−/− mice became less active and ran less compared with wild-type mice. Conclusions Nox4 derived H2O2 plays a key role in exercise-induced adaptations of eNOS and Ppargc1a pathway and intracellular calcium release. Hence, loss of Nox4 diminished physical activity performance and vascular protective effects of exercise. Acknowledgement/Funding This work was supported by a research grant of the German Cardiac Society (DGK) (to H.L.) and DFG (Grant MO 1695/4-1 to H.M.).

Effects Of 3 Days Of High Fat Diet On Exercise-induced Growth Hormone Response In Men

2014 ◽  
Vol 46 ◽  
pp. 403
Author(s):  
Hiroto Sasaki ◽  
Yoshihumi Tsuchiya ◽  
Nobuhiro Shimura ◽  
Aya Ishibashi ◽  
Kumiko Ebi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
High Fat Diet ◽  
Growth Hormone Response ◽  
Hormone Response ◽  
High Fat ◽  
Exercise Induced

Exercise-induced changes of MCT1 in cardiac and skeletal muscles of diabetic rats induced by high-fat diet and STZ

2013 ◽  
Vol 69 (4) ◽  
pp. 865-877 ◽  
Author(s):  
Rohollah Nikooie ◽  
Hamid Rajabi ◽  
Reza Gharakhanlu ◽  
Fereshteh Atabi ◽  
Kobra Omidfar ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Skeletal Muscles ◽  
Diabetic Rats ◽  
High Fat ◽  
Exercise Induced ◽  
Induced Changes

scholarly journals Reduced cortical BACE1 content with one bout of exercise is accompanied by declines in AMPK, Akt, and MAPK signaling in obese, glucose-intolerant mice

2015 ◽  
Vol 119 (10) ◽  
pp. 1097-1104 ◽  
Author(s):  
R. E. K. MacPherson ◽  
P. Baumeister ◽  
W. T. Peppler ◽  
D. C. Wright ◽  
J. P. Little
Keyword(s):  
High Fat Diet ◽  
Recovery Period ◽  
Significant Risk ◽  
Mapk Signaling ◽  
Treadmill Running ◽  
High Fat ◽  
Cellular Mechanisms ◽  
Ampk Signaling ◽  
Erk Phosphorylation ◽  
Single Bout

Obesity and type 2 diabetes are significant risk factors in the development of neurodegenerative diseases, such as Alzheimer's disease. A variety of cellular mechanisms, such as altered Akt and AMPK and increased inflammatory signaling, contribute to neurodegeneration. Exercise training can improve markers of neurodegeneration, but the underlying mechanisms remain unknown. The purpose of this study was to determine the effects of a single bout of exercise on markers of neurodegeneration and inflammation in brains from mice fed a high-fat diet. Male C57BL/6 mice were fed a low (LFD; 10% kcal from lard)- or a high-fat diet (HFD; 60% kcal from lard) for 7 wk. HFD mice underwent an acute bout of exercise (treadmill running: 15 m/min, 5% incline, 120 min) followed by a recovery period of 2 h. The HFD increased body mass and glucose intolerance (both P < 0.05). This was accompanied by an approximately twofold increase in the phosphorylation of Akt, ERK, and GSK in the cortex ( P < 0.05). Following exercise, there was a decrease in beta-site amyloid precursor protein cleaving enzyme 1 (BACE1; P < 0.05) and activity ( P < 0.001). This was accompanied by a reduction in AMPK phosphorylation, indicative of a decline in cellular stress ( P < 0.05). Akt and ERK phosphorylation were decreased following exercise in HFD mice to a level similar to that of the LFD mice ( P < 0.05). This study demonstrates that a single bout of exercise can reduce BACE1 content and activity independent of changes in adiposity. This effect is associated with reductions in Akt, ERK, and AMPK signaling in the cortex.

scholarly journals Consumption of a High-Fat Diet Alters Perineuronal Nets in the Prefrontal Cortex

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
P. M. Dingess ◽  
J. H. Harkness ◽  
M. Slaker ◽  
Z. Zhang ◽  
S. S. Wulff ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Weight Gain ◽  
High Fat Diet ◽  
Spine Density ◽  
Structural Adaptation ◽  
High Fat ◽  
Perineuronal Net ◽  
Key Factor ◽  
Ad Libitum ◽  
Induced Changes

A key factor in the development of obesity is the overconsumption of fatty foods, which, in addition to facilitating weight gain, alters neuronal structures within brain reward circuitry. Our previous work demonstrates that sustained consumption of a high-fat diet (HFD) attenuates spine density in the prefrontal cortex (PFC). Whether HFD promotes structural adaptation among inhibitory cells of the PFC is presently unknown. One structure of interest is the perineuronal net (PNN), a specialized extracellular matrix surrounding, primarily, parvalbumin-containing GABAergic interneurons. PNNs contribute to synaptic stabilization, protect against oxidative stress, regulate the ionic microenvironment within cells, and modulate regional excitatory output. To examine diet-induced changes in PNNs, we maintained rats on one of three dietary conditions for 21 days: ad libitum chow, ad libitum 60% high fat (HF-AL), or limited-access calorically matched high fat (HF-CM), which produced no significant change in weight gain or adiposity with respect to chow controls. The PNN “number” and intensity were then quantified in the prelimbic (PL-PFC), infralimbic (IL-PFC), and ventral orbitofrontal cortex (OFC) using Wisteria floribunda agglutinin (WFA). Our results demonstrated that fat exposure, independent of weight gain, induced a robust decrease in the PNN intensity in the PL-PFC and OFC and a decrease in the PNN number in the OFC.

scholarly journals PPARg Dysfunction in the Medial Prefrontal Cortex Mediates High-Fat Diet-Induced Depression

2021 ◽  
Author(s):  
Cong-Cong Fu ◽  
Xin-Yi Zhang ◽  
Liu Xu ◽  
Hui-Xian Huang ◽  
Shuang Xu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Bidirectional Association

Abstract ObjectiveEpidemiological studies suggest a bidirectional association between depression and obesity; however, the biological mechanisms that link the development of depression to a metabolic disorder remain unclear. Even though nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) agonists show anti-depressive effect, and high-fat diet-(HFD)-induced PPARγ dysfunction is involved in the pathogenesis of metabolic disorders, the neuronal PPARg has never been studied in HFD-induced depression. Thus, we aimed to investigate the effect of neuronal PPARγ on depressive-like behaviors in HFD-induced obese mice. MethodsWe fed male C57BL/6J mice with HFD to generate obese mice and conducted a series of behavioral tests to assess the effects of HFD feeding on depression. We generated neuron-specific PPARγ knockout mice (NKO) to determine whether neuronal PPARg deficiency was correlated with depressive-like behaviors. To further prove whether PPARγ in the medial prefrontal cortex (mPFC) neurons is involved in depressive-like behaviors, we applied AAV- CaMKIIa-Cre approach to specifically knockout PPARγ in the mPFC neurons of LoxP mice and used AAV-syn-PPARγ vectors to overexpress PPARγ in the mPFC neurons of NKO mice. ResultsWe observed a low mPFC PPARγ level and an increase in depressive-like behaviors in the HFD-fed mice. Moreover, neuronal-specific PPARγ deficiency in mice induced depressive-like behaviors, which could be abolished by imipramine. Furthermore, overexpressing PPARg in the mPFC reversed the depressive-like behaviors in HFD-fed mice as well as in neuronal-specific PPARγ knockout mice. ConclusionsThese results implicate that dysregulation of neuronal PPARγ in the mPFC may contribute to an increased risk for depression in obese populations.

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