Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

Background: Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Scope of review: Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Major conclusions: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders. Keywords: Insulin, Intranasal insulin, Memory, Metabolism, Moo

Методология синтеза архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки

Предложен подход к проектированию архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки в реальном времени, основанный на классификации решаемых функциональных задач на основе методов кластерного анализа и выбранного множества признаков подобия. Разработанный подход позволяет из множества функций системы выделить подобные (по определенным признакам) и объединить их в архитектурные компоненты (унифицированные функциональные модули).Запропоновано підхід до проектування архітектури центру обробки інформації автоматизованої системи моніторингу середовища в реальному часі, що заснований на класифікації функціональних задач на підставі методів кластерного аналізу і обраної множини ознак схожості. Розроблений підхід дозволяє вибрати із множини функцій системи схожі (за певними ознаками) і поєднати їх в архітектурні компоненти (уніфіковані функціональні модулі).The approach to designing architecture of the information processing complex of the automated real time conditions monitoring system based on classification of functional tasks on the basis of methods of cluster analysis and the chosen set of similarity attributes is offered. The developed approach allows to allocate from a set of functions the systems similar (on certain attributes) and to unite them in architectural components (unified functional modules)

The effects of long-term saturated fat enriched diets on the brain lipidome

The brain is highly enriched in lipids, where they influence neurotransmission, synaptic plasticity and inflammation. Non-pathological modulation of the brain lipidome has not been previously reported and few studies have investigated the interplay between plasma lipid homeostasis relative to cerebral lipids. This study explored whether changes in plasma lipids induced by chronic consumption of a well-tolerated diet enriched in saturated fatty acids (SFA) was associated with parallel changes in cerebral lipid homeostasis. Male C57Bl/6 mice were fed regular chow or the SFA diet for six months. Plasma, hippocampus (HPF) and cerebral cortex (CTX) lipids were analysed by LC-ESI-MS/MS. A total of 348 lipid species were determined, comprising 25 lipid classes. The general abundance of HPF and CTX lipids was comparable in SFA fed mice versus controls, despite substantial differences in plasma lipid-class abundance. However, significant differences in 50 specific lipid species were identified as a consequence of SFA treatment, restricted to phosphatidylcholine (PC), phosphatidylethanolamine (PE), alkyl-PC, alkenyl-PC, alkyl-PE, alkenyl-PE, cholesterol ester (CE), diacylglycerol (DG), phosphatidylinositol (PI) and phosphatidylserine (PS) classes. Partial least squares regression of the HPF/CTX lipidome versus plasma lipidome revealed the plasma lipidome could account for a substantial proportion of variation. The findings demonstrate that cerebral abundance of specific lipid species is strongly associated with plasma lipid homeostasis

Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity.

BACKGROUND: Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. METHODOLOGY: Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. CONCLUSION: In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on brain mitochondrial function.

<p>Each panel represented brain mitochondrial ROS production (A), brain mitochondrial membrane potential changes (B), brain mitochondrial morphological changes (C) and brain mitochondrial swelling (D). *<i>P</i><0.05 vs. Normal diet treated with vehicle (NDV); ^†<i>P</i><0.05 vs. HFe treated with vehicle (HFeV); ^‡<i>P</i><0.05 vs. HFe treated with either L1 or NAC (HFeL1 or HFeNAC). ND: normal diet fed groups; HFe: high-iron diet fed groups; L1: deferiprone; NAC: n-acetyl cysteine.</p

Effects of the pharmacological interventions on body weight, plasma NTBI, plasma MDA, brain MDA and brain iron level in high iron diet-fed rats.

<p>p<0.05 vs. Normal diet-fed rats,</p><p>p<0.05 vs. High iron diet-fed rats treated with vehicle,</p><p>p<0.05 vs. High iron diet-fed rats treated with either L1 or NAC. ND; normal diet-fed rats, HFe; high iron diet-fed rats, V; vehicle, L1; deferiprone, NAC; n-acetyl cysteine, NTBI; non-transferrin bound iron, MDA; malondialdehyde.</p

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on brain synaptic plasticity.

<p>Each panel represented brain synaptic plasticity in NDV vs. HFeV (A), ND groups (B) and HFe groups (C). ND: normal diet fed group; HFe: high iron diet fed group; L1: deferiprone; NAC: n-acetyl cysteine.</p

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on BBB breakdown and apoptosis.

<p>Each panel represented the expression of tight junction protein; occludin (A), apoptotic-protein; Bax (B) and anti-apoptotic protein; Bcl-2 (C) and Bax/Bcl-2 ratio (D). *<i>P</i><0.05 vs. Normal diet treated with vehicle (NDV); ^†<i>P</i><0.05 vs. HFe treated with vehicle (HFeV); ^‡<i>P</i><0.05 vs. HFe treated with either L1 or NAC (HFeL1 or HFeNAC). ND: normal diet fed groups; HFe: high-iron diet fed groups; L1: deferiprone; NAC: n-acetyl cysteine.</p

Effects of the pharmacological interventions by deferiprone and n-acetyl cysteine on learning and memory behavior.

<p>Each panel represented locomotors activity (A) and learning and memory behavior indicated by time to reach platform (B, D and F) and time spent in target quadrant (C and E). *<i>P</i><0.05 vs. Normal diet treated with vehicle (NDV); ^†<i>P</i><0.05 vs. HFe treated with vehicle (HFeV); ^‡<i>P</i><0.05 vs. HFe treated with either L1 or NAC (HFeL1 or HFeNAC). ND: normal diet fed groups; HFe: high-iron diet fed groups; L1: deferiprone; NAC: n-acetyl cysteine.</p