The interneuron energy hypothesis: Implications for brain disease

Kann, Oliver

doi:10.1016/j.nbd.2015.08.005

Cited by 216 publications

(244 citation statements)

References 201 publications

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“…These interneurons require large amounts of energy and feature a high oxygen consumption rate to maintain cognitive function. The decreased availability of ATP in aging and AD especially affects these fast-spiking GABAergic interneurons and thus leads to impaired cognitive function including memory formation, motor behavior and sensory perception (Kann 2015). This link between brain mitochondrial and cognitive function gives a good explanation for the impaired performance of aged NMRI mice and the greatly improved performance of aged NMRI mice administered RBE that we observed during our study in the passive avoidance and Y-maze test.…”

Section: Behavioral Testingsupporting

confidence: 62%

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice

et al. 2016

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Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer's disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feeding studies. To mimic the use of RBE as food additive, we have now investigated the effects of a long-term (6 months) feeding of RBE on survival, behavior and brain mitochondrial function in aged NMRI mice. RBE administration significantly increased survival and performance of aged NMRI mice in the passive avoidance and Y-maze test. Brain mitochondrial dysfunction found in aged mice was ameliorated after RBE administration. Furthermore, data from mRNA and protein expression studies revealed an up-regulation of mitochondrial proteins in RBE-fed mice, suggesting an increase in mitochondrial content which is mediated by a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-dependent mechanism. Our findings suggest that a long-term treatment with a nutraceutical containing RBE could be useful for slowing down brain aging and thereby delaying or even preventing AD.

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Section: Behavioral Testingsupporting

confidence: 62%

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice

et al. 2016

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“…Furthermore, converging evidence suggests that shifts in excitatory/inhibitory balance in vulnerable cortical circuits are significant drivers in the pathophysiological progression of Alzheimer disease. 31 Interestingly, most of the correlation abnormalities involved the DMN regions, which are structures known to be hit by the pathophysiological process in Alzheimer disease. 9 For instance, it has repeatedly been demonstrated in PiB-PET studies that the presence of amyloid plaques is sufficient for there to be functional connectivity changes not only in the DMN, 10 but also in the SAL and ECN 32 and even between networks.…”

Section: Discussionmentioning

confidence: 99%

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels

Weiler

Campos

Teixeira

et al. 2017

JPN

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“…Decreased PPAR expression in the adipose tissue (20) of hypercholesterolemic mice was related to a modified expression of the genes that explain decreased insulin sensitivity and glucose transport, elevated hypertriglyceridemia, inflammation, and increased oxidative stress. The association of insulin sensitivity (21), glucose transport (22), elevated hypertriglyceridemia (23), inflammation (17,24), and increased oxidative stress (25) with AD has already been established. In the current study, measurement of brain weight in the test group showed no change in brain wet weight, which supported findings in another study (11).…”

Section: Discussionmentioning

confidence: 99%

High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory

Nikasa¹,

Karimi²,

Rajavand³

et al. 2016

Iran Red Crescent Med J

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Background: Abnormal cholesterol homeostasis is associated with the pathogenesis of neurodegenerative disease and cognitive impairment. Objectives: Our objective was to evaluate changes in the expression of proteins related to cognition and cholesterol homeostasis in the hippocampi of rats as well as behavioral modifications following the administration of a cholesterol-rich diet. Methods: In this experimental study, lasting 16 weeks, 20 male Wistar rats (aged 8 weeks) were randomly divided into two groups. One group was fed with a normal diet (ND; n = 10) and the second with a high cholesterol diet (HD; n = 10). The expression of the cognition-related proteins N-methyl-D-aspartate receptor (NMDAR) and beta-secretase 1 (BACE1) and cholesterol 24-hydroxylase (CYP46A1), the key cholesterol hemostasis protein, were determined by an immunoblotting assay in the hippocampus homogenate. The Morris water maze (MWM) test was used to examine cognitive performance. Plasma lipidic parameters, including total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG), as well as brain TC were measured by colorimetric assay. Results: After a high cholesterol diet had been administered for a period of 16 weeks, a significant increase in TC, LDL-C and TG was observed in the HD group in comparison with the ND group (P < 0.05). Neither the mean of brain wet weight nor brain TC showed significant change in the HD versus the ND group (P = 0.114, P = 0.84, respectively). Despite this fixity, differences in the expression of BACE1 and CYP46A1 were significant (P < 0.05) between the two groups, with high levels of BACE1 and CYP46A1 in the HD group compared with the ND group. These biochemical changes were associated with a significant decrease in the time traveled on a platform quadrant in the HD versus the ND group (P < 0.05) during a spatial memory probe test administered at the same time. Conclusions:The findings show that irregularities in cognitive performance as a result of a high cholesterol diet can be partially mediated by distortion in brain cholesterol homeostasis and processing of the amyloid precursor protein (APP).

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The interneuron energy hypothesis: Implications for brain disease

Cited by 216 publications

References 201 publications

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels

High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory

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