AbetaPP is involved in Cu homeostasis in mouse and man. In vitro observations and in vivo data obtained from AbetaPP mouse models at least provide strong evidence that AbetaPP and Abeta overproduction enables intracellular Cu to be transported out of the cell. The increased Cu efflux seems to lead to ...

Cognitive function and peripheral glucose regulation both decrease with age. There is a consistent and growing literature reporting memory and other cognitive problems among individuals with diabetes mellitus as well as those with pre-diabetes. There are two papers in the literature documenting, relative to matched controls, hippocampal volume reductions among ...

The central hypothesis examined in this issue is that insulin resistance promotes maladaptive brain function and contributes to reduced neuronal plasticity, potentially accelerating brain aging. Therefore, if we were to prevent or treat insulin resistance, through weight loss and exercise, cognitive function would be improved. In this article, we argue ...

The role of polysaccharides in the pathogenesis of Alzheimer disease (AD) is unclear. However, in light of studies indicating impaired glucose utilization in AD and increased activation of the hexosamine pathway that is seen with hyperglycemia, in the brains of patients with AD, aberrantly high levels of glucosamine may result ...

This article presents an overview of the most recent and important strategies to reduce secondary brain damage. There is currently no magic bullet available to protect the brain after neuronal injury. This is related to the complex pathophysiology of cerebral ischemia, which makes it unlikely that a single pharmacological intervention ...

Statins may have favorable effects on endothelial barrier function. The effect of rosuvastatin and simvastatin therapy (10 mg/kg) for 5 weeks on blood-brain barrier (BBB), blood-retinal barrier (BRB), and cardiac muscle permeability of streptozotocin-induced diabetic rats was studied. The size-selective permeability of different vascular beds to a group of fluorescein ...

OBJECTIVES: In patients with Klinefelter syndrome dissocial behaviour, learning difficulties and low intelligence are common. Thus, the aim of our study was to perform brain perfusion studies and cranial cephalometry in 27 cases of Klinefelter syndrome and compare the results with those in a group of 26 healthy subjects. METHODS: ...

Brain microglia are phagocytic cells that are the major inflammatory response cells of the central nervous system and widely held to play important pathophysiologic roles in Alzheimer's disease (AD) in both potentially neurotoxic responses and potentially beneficial phagocytic responses. In the study, we examined whether ginsonoside Rg3, a by-product of ...

BACKGROUND: Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (Abeta). Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network. OBJECTIVES: To determine the effects of ...

Hyperglycemia and ketoacidosis are the two most serious factors in acute metabolic complications of both type 1 and type 2 diabetes. Dysfunction of the central nervous system is a well-documented complication of diabetes. We and others have previously reported that acute or chronic diabetes in animal's results in altered brain ...

The goal of this study was to further explore potential mechanisms through which diabetogenic dietary conditions that result in promotion of insulin resistance (IR), a feature of non-insulin dependant diabetes mellitus (type-2 diabetes), may influence Alzheimer's disease (AD). Using genome-wide array technology, we found that connective tissue growth factor (CTGF), ...

Insulin regulates the phosphorylation and activities of Akt and glycogen synthase kinase-3 (GSK3) in peripheral tissues, but in the brain it is less clear how this signaling pathway is regulated in vivo and whether it is affected by diabetes. We found that Akt and GSK3 are sensitive to glucose, because ...

Brain atrophy in diabetic dementia (DD) may be due to a catabolic state with DNA loss. Insulin-like growth factor (IGF) levels are reduced in diabetes, and IGF replacement may ameliorate brain protein loss. Subcutaneous minipumps released vehicle (Db + Veh) or IGF-I (Db + IGF-I) in diabetic rats. Brain wet, ...

OBJECTIVE: The positron emission tomography (PET) clinical utility of the sensitivity (gamma) of uptake (Q) to a change in plasma glucose concentration (C) is investigated. METHODS: Gamma is obtained from data as [ln(Q (2)/Q (1))] / [ln(C(2)/C(1))], using previously published intrapatient studies varying C within a single patient and some ...

Chronic diabetes is associated with the alteration of second messengers and CNS disorders. We have recently identified that protein kinases (CaMKII and PKC-alpha) and brain neurotransmitters are altered during diabetes as well as in hyperglycemic and acidotic conditions. In this study, we investigated the effects of acute diabetes on the ...

PURPOSE: To prospectively determine whether there is an association between brain white matter signal hyperintensities on magnetic resonance (MR) images and potential risk factors for cerebral ischemia in a well-characterized narrow age cohort of nondemented community-dwelling elderly people. MATERIALS AND METHODS: The study population consisted of surviving members of the ...

Hyperglycemia and diabetes alter the function and metabolism of many tissues. The effect on the brain remains poorly defined, but some animal data suggest that chronic hyperglycemia reduces rates of brain glucose transport and/or metabolism. To address this question in human beings, we measured glucose in the occipital cortex of ...

Transiently low blood glucose levels are common in the neonatal period and may be considered a normal feature of adaptation to extrauterine life. There is no evidence that this causes brain injury in the absence of concurrent clinical manifestations. Conversely, persistent and severe hypoglycaemia may be associated with other underlying ...

Microglia rapidly become reactive in response to diverse stimuli and are thought to be prominent participants in the pathophysiology of both acute injury and chronic neurological diseases. However, mature microglial reactions to a focal lesion have not been characterized dynamically in adult vertebrate tissue. Here, we present a detailed analysis ...

Laterality is fundamental to the vertebrate body plan. Here, we investigate the roles of fgf8 signaling in LR patterning of the zebrafish embryo. We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. When fgf8 is absent, nodal signaling is randomized in the lateral ...

The persistent vegetative state (PVS) and the minimally conscious state (MCS) are conditions of altered consciousness after severe brain damage due to a variety of pathologies. However, the specific pathophysiological mechanisms and a therapeutic strategy for intervention have not as yet been established. We review previous reports of levodopa treatment ...

The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the ...

OBJECTIVE: Children who develop type 1 diabetes before age 7 years (early-onset diabetes; EOD) have comparatively poorer cognitive abilities. Whether this relates to psychosocial consequences of chronic illness or organic factors related to diabetes and its complications remains unresolved. We hypothesized that if differences in neuroradiological structure and cognitive ability ...

Hyperglycemia and acidosis are the key factors in diabetic complications. It has been shown that acute or chronic diabetes alters serotonin levels in brain. However, the mechanism of hyperglycemia- or acidosis-induced changes in serotonin levels remains poorly understood. Because Ca2+-dependent protein kinases play a major role in the regulation of ...

AIMS: Type 1 diabetes is a prevalent chronic disease in childhood with the commonest single cause of death being cerebral oedema in the context of diabetic ketoacidosis (DKA). The nature of the alterations in cerebral metabolism that may result in vulnerability to neuronal injury remains unknown. The aim of this ...

Diabetes and hypertension are potent risk factors for cerebrovascular disease. We studied the effects of an angiotensin II type 1 receptor blockade (ARB) on brain damage in hypertensives in relation to diabetes. We studied cerebral metabolism (by proton magnetic resonance spectroscopy) and hemodynamics (by phase-contrast magnetic resonance angiography) before and ...

BACKGROUND: Magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are found at higher rates in patients with affective disorders, particularly late-life or treatment-resistant disorders. Studies support a vascular pathogenesis for WMHs in late-life onset disorders; however, pathogenesis in typical early-life onset disorders is less clear. Based on associations between diabetes ...

To clarify the mechanism of hyperaccumulation of glucose in acute brain ischemia by PET, changes of glucose metabolism and mitochondrial electron transfer function were examined in living brain slices in vitro during control, hypoxic, and anoxic conditions by positron autoradiography using [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [(15)O]oxygen. [(15)O]Oxygen fixation reflecting mitochondrial electron ...

Many diabetic individuals develop anosmia but the mechanism(s) causing the dysfunction in the olfactory system is (are) unknown. Glial fibrillary acidic protein expression is reduced in diabetic retinopathy and is also reduced, with unknown consequences, in other brain regions of diabetic rats. We used immunohistochemistry and immunoblotting from untreated control ...

Peri-infarct depolarisations (PIDs) contribute to infarct expansion in experimental focal ischaemia; furthermore, depolarisations propagate in the injured human brain. Glucose utilisation is increased under both conditions, and depletion of brain glucose carries a poor prognosis. We studied dynamics of cerebral glucose and lactate in relation to PID patterns in experimental ...

Yawning is contagious: Watching another person yawn may trigger us to do the same. Here we studied brain activation with functional magnetic resonance imaging (fMRI) while subjects watched videotaped yawns. Significant increases in the blood oxygen level dependent (BOLD) signal, specific to yawn viewing as contrasted to viewing non-nameable mouth ...

In the present study we report results on the possible mechanism of inhibition of tryptophan-5-hydroxylase activity induced by insulin-dependent diabetes mellitus (IDDM). Kinetic experiments were done with different L-tryptophan (L-Trp) concentrations in the rat brain at different days of evolution of the disease. Additionally, different activation conditions of the enzyme ...

In patients with the frontal variant of frontotemporal lobar degeneration (fv-FTLD), behavioral abnormalities may vary from apathy with motor slowness (apathetic form) to disinhibition with agitation (disinhibited form). These clinical presentations may be related to specific regional cerebral dysfunction and to deficit in the serotoninergic system. We studied cerebral glucose ...

Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics ...

In the present work, several experimental approaches were used to determine the presence of the glucagon-like peptide-1 receptor (GLP-1R) and the biological actions of its ligand in the human brain. In situ hybridization histochemistry revealed specific labelling for GLP-1 receptor mRNA in several brain areas. In addition, GLP-1R, glucose transporter ...

Increasingly, data from epidemiologic studies suggest diabetes is a risk factor in old age for brain aging, including cognitive impairment and dementia. These associations may reflect a direct effect on the brain of hyperglycemia, or the effects of the diabetes-associated comorbidities of hypertension, dyslipidemia, or hyperinsulinemia. Epidemiologic data on diabetes ...

Recent evidence suggests a key role for the brain in the control of both body fat content and glucose metabolism. Neuronal systems that regulate energy intake, energy expenditure, and endogenous glucose production sense and respond to input from hormonal and nutrient-related signals that convey information regarding both body energy stores ...

Glucose is absolutely essential for the survival and function of the brain. In our current understanding, there is no endogenous glucose production in the brain, and it is totally dependent upon blood glucose. This glucose is generated between meals by the hydrolysis of glucose-6-phosphate (Glc-6-P) in the liver and the ...

BACKGROUND: This study aimed to analyze the relation of hyperglycemia to outcome in cases of severe traumatic brain injury, and to examine factors that may be responsible for the hyperglycemic state. METHODS: A retrospective analysis in an intensive care unit of a level 1 trauma center investigated 77 patients with ...

In this study, maximize a posterior approach (MAP) was applied for detailed imaging of the glucose metabolism in the brain using PET and ¹⁸F-FDG. FDG is a glucose analog and it can investigate a glucose metabolism. In PET studies, glucose metabolism can be measured to estimate a compartment model which ...

Stroke is a very complex disease influenced by many risk factors: genetic, environmental and comorbidities, such as hypertension, diabetes mellitus, obesity and having had a previous stroke. Neuroprotective therapies that have been found to be successful in laboratory animals have failed to produce the same benefits in clinical trials. Currently, ...

The hippocampus, an important integration center for learning and memory in the mammalian brain, undergoes neurological changes in response to a variety of stimuli that are suggestive of ongoing synaptic reorganization. Accordingly, the aim of this study was to identify markers of synaptic plasticity using rapid and reliable techniques such ...

Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three ...

We reported that a leaf extract (GLEt) obtained from an anti-diabetic plant, Gymnema montanum, an endangered species endemic to India, has anti-peroxidative and antioxidant effects on diabetic brain tissue in rats. Here we examined the effect of the extract on the activity of reduced brain and retinal acetylcholinesterase (AChE) and ...

OBJECTIVE: To investigate group differences and correlations and to determine the sensitivity and specificity of different measures of the neuronal marker N-acetylaspartate (NAA) in the medial temporal lobe of Alzheimer's Disease (AD) patients. METHODS: The metabolic ratio NAA/creatine (Cr), the absolute concentration of NAA referenced against brain tissue (BT) water ...

Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related ...

Obesity is quickly becoming one of the most common and debilitating disorders of the developed world. More than 60% of American adults are now overweight or obese, predisposing them to a host of chronic diseases. To understand the etiology of obesity, and to discover new therapies for obesity, we must ...

The authors report a rare meningioma-primary cerebral B cell lymphoma association that occurred in an insulin-dependent type-I diabetic woman. The woman was initially operated on because of meningothelial meningioma of the fronto-basal region, and 2 months later showed a primitive-non-Hodgkin B cell lymphoma, localized in the same area as the ...

Microangiopathic end-organ injury is common in type 1 diabetes. However, the pathophysiology of diabetic encephalopathy is poorly understood. The authors studied 10 normotensive patients with type 1 diabetes with retinopathy, autonomic neuropathy, but without nephropathy, and 10 healthy subjects. Proton magnetic resonance spectroscopy was performed at 1.5 T in the ...

The present study assesses the changes of dopamine levels in the basal ganglia (BG) of rabbit brain during heatstroke with or without hypothermia therapy. The dopamine levels were determined by using 6(F18) fluoro-L-dopa (FDOPA) positron emission tomography (PET) scan. Heatstroke was induced by exposing the anesthetized rabbits to a high ...