scholarly journals Consequences of recurrent hypoglycaemia on brain function in diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Rory J. McCrimmon
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species Generation ◽  
Short Review ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Dark Side ◽  
Glycaemic Variability ◽  
Increased Risk ◽  
The Brain ◽  
Recurrent Hypoglycaemia

AbstractThe discovery of insulin and its subsequent mass manufacture transformed the lives of people with type 1 and 2 diabetes. Insulin, however, was a drug with a ‘dark side’. It brought with it the risk of iatrogenic hypoglycaemia. In this short review, the cellular consequences of recurrent hypoglycaemia, with a particular focus on the brain, are discussed. Using the ventromedial hypothalamus as an exemplar, this review highlights how recurrent hypoglycaemia has an impact on the specialised cells in the brain that are critical to the regulation of glucose homeostasis and the counterregulatory response to hypoglycaemia. In these cells, recurrent hypoglycaemia initiates a series of adaptations that ensure that they are more resilient to subsequent hypoglycaemia, but this leads to impaired hypoglycaemia awareness and a paradoxical increased risk of severe hypoglycaemia. This review also highlights how hypoglycaemia, as an oxidative stressor, may also exacerbate chronic hyperglycaemia-induced increases in oxidative stress and inflammation, leading to damage to vulnerable brain regions (and other end organs) and accelerating cognitive decline. Pre-clinical research indicates that glucose recovery following hypoglycaemia is considered a period where reactive oxygen species generation and oxidative stress are pronounced and can exacerbate the longer-term consequence of chronic hypoglycaemia. It is proposed that prior glycaemic control, hypoglycaemia and the degree of rebound hyperglycaemia interact synergistically to accelerate oxidative stress and inflammation, which may explain why increased glycaemic variability is now increasingly considered a risk factor for the complications of diabetes. Graphical abstract

scholarly journals Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanan Sun ◽  
Cao Ma ◽  
Hui Sun ◽  
Huan Wang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Impaired Insulin ◽  
The Brain

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

scholarly journals Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

2019 ◽  
Vol 116 (15) ◽  
pp. 7503-7512 ◽  
Author(s):  
Liching Lo ◽  
Shenqin Yao ◽  
Dong-Wook Kim ◽  
Ali Cetin ◽  
Julie Harris ◽  
...  
Keyword(s):  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Feed Forward ◽  
Motor Processing ◽  
Central Processing ◽  
Indirect Feedback ◽  
High Level ◽  
High Degree ◽  
The Brain

Type 1 estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvlEsr1) play a causal role in the control of social behaviors, including aggression. Here we use six different viral-genetic tracing methods to systematically map the connectional architecture of VMHvlEsr1 neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (∼90%) of bidirectionality, including both direct as well as indirect feedback. Unbiased collateralization mapping experiments indicate that VMHvlEsr1 neurons project to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization targets. Nevertheless, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired,” hierarchical feed-forward circuits used in certain types of artificial intelligence networks.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress

2016 ◽  
Vol 94 (10) ◽  
pp. 1074-1082 ◽  
Author(s):  
Dragan Hrncic ◽  
Jelena Mikić ◽  
Aleksandra Rasic-Markovic ◽  
Milica Velimirović ◽  
Tihomir Stojković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Wistar Rats ◽  
Brain Regions ◽  
Oxidative Status ◽  
Standard Diet ◽  
Male Wistar Rats ◽  
Brain Oxidative Stress ◽  
The Brain

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light–dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

Hormetic effects of regular exercise in aging: correlation with oxidative stress

2007 ◽  
Vol 32 (5) ◽  
pp. 948-953 ◽  
Author(s):  
Sataro Goto ◽  
Hisashi Naito ◽  
Takao Kaneko ◽  
Hae Young Chung ◽  
Zsolt Radák
Keyword(s):  
Oxidative Stress ◽  
Treadmill Exercise ◽  
Reactive Oxygen Species Generation ◽  
Nuclear Factor Κb ◽  
Protein Carbonyl ◽  
Binding Activity ◽  
Regular Exercise ◽  
Inflammatory Reactions ◽  
Old Rats ◽  
The Brain

To explore mechanisms of the beneficial consequences of regular exercise, we studied the effects of regular swimming and treadmill exercise on oxidative stress in the brain and liver of rats. Protein carbonyl was significantly reduced and the activity of proteasome was upregulated in the brain extracts of young and middle-aged animals after 9 weeks of swimming training. Furthermore, their cognitive functions were significantly improved. In separate experiments, the activation of transcription nuclear factor κB was attenuated in the liver of old rats after 8 weeks of regular treadmill exercise and the DNA binding activity of glucocorticoid receptor reduced with age was restored, suggesting that inflammatory reactions are alleviated by the regimen. This was accompanied by upregulation of the glutathione level and reduced reactive oxygen species generation. Similar training reduced the 8-oxodeoxyguanosine content in the nuclear and mitochondrial DNA of the liver of old rats. Thus, these findings, together with reports of other investigators, suggest that moderate regular exercise attenuates oxidative stress. The mild oxidative stress possibly elicited by regular exercise appears to manifest a hormesis-like effect in nonmuscular tissues, constituting beneficial mechanisms of exercise by adaptively upregulating various antioxidant mechanisms, including antioxidative and repair–degradation enzymes for damaged molecules. Importantly, the adaptation induced by regular exercise was effective even if initiated late in life.

scholarly journals Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alfonso Díaz ◽  
Samuel Treviño ◽  
Jorge Guevara ◽  
Guadalupe Muñoz-Arenas ◽  
Eduardo Brambila ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Inflammatory Response ◽  
Temporal Cortex ◽  
Energy Drink ◽  
Brain Regions ◽  
Adult Rats ◽  
Mechanisms Of Toxicity ◽  
The Brain ◽  
And Oxidative Stress

Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.

Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure

2008 ◽  
Vol 24 (4) ◽  
pp. 247-256 ◽  
Author(s):  
D Mishra ◽  
SJS Flora
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Drinking Water ◽  
Wistar Rats ◽  
Arsenic Exposure ◽  
Brain Regions ◽  
Single Strand ◽  
Male Wistar Rats ◽  
Chronic Arsenic Exposure ◽  
The Brain

Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain – parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

Dichlorvos induces differential oxidative stress in the brain regions of rat

2018 ◽  
Vol 3 (5) ◽  
pp. 150-156 ◽  
Author(s):  
Dileepkumar H. V. ◽  
Ritesh K. R.
Keyword(s):  
Oxidative Stress ◽  
Brain Regions ◽  
The Brain

Comparing the risks of frameless stereotactic biopsy in eloquent and noneloquent regions of the brain: a retrospective review of 284 cases

2009 ◽  
Vol 111 (4) ◽  
pp. 820-824 ◽  
Author(s):  
Ellen L. Air ◽  
James L. Leach ◽  
Ronald E. Warnick ◽  
Christopher M. McPherson
Keyword(s):  
Medical Records ◽  
Stereotactic Biopsy ◽  
Brain Regions ◽  
Postoperative Hemorrhage ◽  
Brain Lesions ◽  
Imaging Studies ◽  
Lesion Location ◽  
Biopsy Site ◽  
Increased Risk ◽  
The Brain

Object Frameless stereotactic biopsy has been shown in multiple studies to be a safe and effective tool for the diagnosis of brain lesions. However, no study has directly evaluated its safety in lesions located in eloquent regions in comparison with noneloquent locations. In this study, the authors determine whether an increased risk of neurological decline is associated with biopsy of lesions in eloquent regions of the brain. Methods Medical records, including imaging studies, were reviewed for 284 cases in which frameless stereotactic biopsy procedures were performed by 19 neurosurgeons at 7 institutions between January 2000 and December 2006. Lesion location was classified as eloquent or noneloquent in each patient. The incidence of neurological decline was calculated for each group. Results During the study period, 160 of the 284 biopsies predominately involved eloquent regions of the brain. In evaluation of the complication rate with respect to biopsy site, neurological decline occurred in 9 (5.6%) of 160 biopsies in eloquent brain areas and 10 (8.1%) of 124 biopsies in noneloquent regions; this difference was not statistically significant (p = 0.416). A higher number of needle passes was associated with the presence of a postoperative hemorrhage at the biopsy site, although not with a change in the result of neurological examination. Conclusions Frameless stereotactic biopsy of lesions located in eloquent brain regions is as safe and effective as biopsy of lesions in noneloquent regions. Therefore, with careful planning, frameless stereotactic biopsy remains a valuable and safe tool for diagnosis of brain lesions, independent of lesion location.

scholarly journals A systematic review of neuroimaging and acute cannabis exposure in age-of-risk for psychosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lani Cupo ◽  
Eric Plitman ◽  
Elisa Guma ◽  
M. Mallar Chakravarty
Keyword(s):  
Chronic Exposure ◽  
Brain Regions ◽  
Acute Exposure ◽  
Psychotic Symptoms ◽  
Long Term Effects ◽  
Symptom Dimensions ◽  
Increased Risk ◽  
The Impact ◽  
The Brain

AbstractAcute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discovered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.

Sign in / Sign up

Export Citation Format

Share Document