Effect of coenzyme Q10 and vitamin E on brain energy metabolism in the animal model of Huntington's disease

The neuropathological and clinical symptoms of Huntington's disease (HD) can be simulated in animal model with systemic administration of 3-nitropropionic acid (3-NP). Energy defects in HD could be ameliorated by administration of coenzyme Q10 (CoQ10), creatine, or nicotinamid. We studied the activity of creatine kinase (CK) and the function of mitochondrial respiratory chain in the brain of aged rats administered with 3-NP with and without previous application of antioxidants CoQ10 + vitamin E. We used dynamic and steady-state methods of in vivo phosphorus magnetic resonance spectroscopy (31P MRS) for determination of the pseudo-first order rate constant (kfor) of the forward CK reaction, the phosphocreatine (PCr) to adenosinetriphosphate (ATP) ratio, intracellular pHi and Mgi 2+ content in the brain. The respiratory chain function of isolated mitochondria was assessed polarographically; the concentration of CoQ10 and α-tocopherol by HPLC. We found significant elevation of kfor in brains of 3-NP rats, reflecting increased rate of CK reaction in cytosol. The function of respiratory chain in the presence of succinate was severely diminished. The activity of cytochromeoxidase and mitochondrial concentration of CoQ 10 was unaltered; tissue content of CoQ10 was decreased in 3-NP rats. Antioxidants CoQ10 + vitamin E prevented increase of kfor and the decrease of CoQ10 content in brain tissue, but were ineffective to prevent the decline of respiratory chain function. We suppose that increased activity of CK system could be compensatory to decreased mitochondrial ATP production, and CoQ10 + vitamin E could prevent the increase of kfor after 3-NP treatment likely by activity of CoQ 10 outside the mitochondria. Results of our experiments contributed to elucidation of mechanism of beneficial effect of CoQ10 administration in HD and showed that the rate constant of CK is a sensitive indicator of brain energy disorder reflecting therapeutic effect of drugs that could be used as a new in vivo biomarker of neurodegenerative diseases. © 2005 Elsevier Ltd. All rights reserved

Omega-3-PUFA, omega-6-PUFA and mitochondrial dysfunction in relation to remodelling

Metabolic syndrome may be a disease of the brain related to Western diet-induced proinflammatory damage of the arcuate nucleus and POMC neurons in the brain, as well as to damage of beta cells in the pancreas. Consumption of a Western diet and eating late at night can double the adverse effects of diet by causing systemic inflammation and damage to the circadian clock machinery, leading to circadian disruption, resulting in metabolic syndrome due to low melatonin and leptin and high cortisol and ghrelin. These neurotransmitters are known to increase oxidative stress, which may damage certain areas of the brain, endothelial cells, and myocardial cells via subcellular remodeling. Increases in free radicals may damage other neurons, macrophages, hepatocytes in the liver, β-cells in the pancreas, and endothelial cells and smooth muscle cells, due to the release of proinflammatory cytokines. Pro-inflammatory cytokines, in conjunction with an underlying deficiency of long-chain PUFA, CoQ10, and polyphenolics, and excess of omega-6-fatty acids, may damage cells in various organs, including pancreatic β-cells, resulting in a further increase in insulin resistance, metabolic syndrome, and diabetes mellitus. © 2018 Nova Science Publishers, Inc. All rights reserved

Omega-3-PUFA, omega-6-PUFA and mitochondrial dysfunction in relation to remodelling

Metabolic syndrome may be a disease of the brain related to Western diet-induced proinflammatory damage of the arcuate nucleus and POMC neurons in the brain, as well as to damage of beta cells in the pancreas. Consumption of a Western diet and eating late at night can double the adverse effects of diet by causing systemic inflammation and damage to the circadian clock machinery, leading to circadian disruption, resulting in metabolic syndrome due to low melatonin and leptin and high cortisol and ghrelin. These neurotransmitters are known to increase oxidative stress, which may damage certain areas of the brain, endothelial cells, and myocardial cells via subcellular remodeling. Increases in free radicals may damage other neurons, macrophages, hepatocytes in the liver, β-cells in the pancreas, and endothelial cells and smooth muscle cells, due to the release of proinflammatory cytokines. Pro-inflammatory cytokines, in conjunction with an underlying deficiency of long-chain PUFA, CoQ10, and polyphenolics, and excess of omega-6-fatty acids, may damage cells in various organs, including pancreatic β-cells, resulting in a further increase in insulin resistance, metabolic syndrome, and diabetes mellitus. © 2018 Nova Science Publishers, Inc. All rights reserved

Can climate, weather, cosmos, and environmental degradation predispose to cardiovascular and other diseases?

The internal environment of our body systems interacts with environment in the biosphere and cosmos; the earth rotates around its axis, and around the sun in the cosmos, all living species, including humans, animals and plants, are exposed to storms induced by solar activity, geomagnetic activity, cosmic ray activity and gravitational activity. Magnetic storms may be responsible for changes in climate weather in the biosphere and cosmos as well as on earth which may influence physiology and metabolisms as well as physio-pathogenesis of diseases. Cosmology is the science dealing with knowledge about origin and development of universe, including biology related to the cosmos. Therefore, it is pertinent to call cosmo-biology, when dealing with effects of the cosmos on biological functions. Mental and spiritual health, and also possibly physical and social health, may be under the influence of solar activity, geomagnetic activity and cosmic ray activity that have major effects on space weather and climate in the cosmos. Environmental degradation may disturb magnetic activity in the cosmos, leading to changes in climate with increase in environmental temperatures causing longer summer heat waves that increase mortality, particularly among vulnerable populations such as elderly and poor people, residents of urban heat islands, and people with mental illness. Higher temperatures also increase ozone levels, compromising lung function and exacerbating asthma which may worsen due to earlier and longer pollen seasons, elevating exposure to allergens and increasing allergic sensitization and asthma episodes. Higher temperatures may result in larger and longer forest fires, reducing downwind air quality and increasing hospitalizations for respiratory and cardiovascular conditions like heart attack and sudden death. Increases in temperatures above 40°C may also predispose to heart attack. © 2018, Nova Science Publishers, Inc.. All rights reserved

Brain-heart interactions and circadian rhythms in chronic heart failure (homage to Dr. Franz Halberg on the 2nd anniversary of his death on 9th june 2013)

Background. Professor Franz Halberg contributed greatly to our understanding of the importance of chronobiology in prevention, intervention, and treatment of CVD: hence this article of remembrance. Clinical and biochemical manifestations of chronic heart failure (HF) may be due to interactions of the brain and the heart. Circadian rhythms may be lost via neuro-humoral adaptations, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems in the brain, heart, and peripheral vessels in a milieu of melatonin deficiency. Methods. Internet and database searches and discussion with colleagues. Results. Experimental and clinical evidence indicates that chronic HF may be associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, with the target of involvement being the heart. Brain-heart interactions may result from an increased systemic and cerebral angiotensin II signaling since plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites causing increased contractility of the heart, as an adaptation, during chronic HF. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM) and area postrema (AP) via neuregulin-brain natriuretic peptide release from these sites which influences the function of cardiomyocytes and the heart. We propose that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. Experimental studies indicate that administration of an angiotensin receptor blocker by injection into the AP activates the sympatho-inhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity which has a beneficial effect on cardiomyocyte function. Angiotensin II also elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings in chronic HF resulting in an increase in sympathetic nerve activity. A rise in circulating angiotensin II during chronic HF may increase the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in cardiomyocyte dysfunction and worsening of HF. Conclusion. Brain-heart interactions and damage to the circadian system with increased circulating angiotensin II signaling may directly act on the brain via the subfornical organ and the AP to increase sympathetic outflow and worsening of neurohumoral adaptations leading to chronic HF. © 2016 Nova Science Publishers, Inc

Brain-heart interactions and circadian rhythms in chronic heart failure (Homage to Dr. Franz Halberg on the 2nd anniversary of his death on 9th June 2013)

Background. Professor Franz Halberg contributed greatly to our understanding of the importance of chronobiology in prevention, intervention, and treatment of CVD: hence this article of remembrance. Clinical and biochemical manifestations of chronic heart failure (HF) may be due to interactions of the brain and the heart. Circadian rhythms may be lost via neuro-humoral adaptations, such as activation of the renin-angiotensinaldosterone and sympathetic nervous systems in the brain, heart, and peripheral vessels in a milieu of melatonin deficiency. Methods. Internet and database searches and discussion with colleagues. Results. Experimental and clinical evidence indicates that chronic HF may be associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, with the target of involvement being the heart. Brain-heart interactions may result from an increased systemic and cerebral angiotensin II signaling since plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites causing increased contractility of the heart, as an adaptation, during chronic HF. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM) and area postrema (AP) via neuregulin-brain natriuretic peptide release from these sites which influences the function of cardiomyocytes and the heart. We propose that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. Experimental studies indicate that administration of an angiotensin receptor blocker by injection into the AP activates the sympathoinhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity which has a beneficial effect on cardiomyocyte function. Angiotensin II also elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings in chronic HF resulting in an increase in sympathetic nerve activity. A rise in circulating angiotensin II during chronic HF may increase the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in cardiomyocyte dysfunction and worsening of HF. Conclusion. Brain-heart interactions and damage to the circadian system with increased circulating angiotensin II signaling may directly act on the brain via the subfornical organ and the AP to increase sympathetic outflow and worsening of neuro-humoral adaptations leading to chronic HF. © 2015 Nova Science Publishers, Inc

Brain-heart interactions and circadian rhythms in chronic heart failure (homage to Dr. Franz Halberg on the 2nd anniversary of his death on 9th june 2013)

Background. Professor Franz Halberg contributed greatly to our understanding of the importance of chronobiology in prevention, intervention, and treatment of CVD: hence this article of remembrance. Clinical and biochemical manifestations of chronic heart failure (HF) may be due to interactions of the brain and the heart. Circadian rhythms may be lost via neuro-humoral adaptations, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems in the brain, heart, and peripheral vessels in a milieu of melatonin deficiency. Methods. Internet and database searches and discussion with colleagues. Results. Experimental and clinical evidence indicates that chronic HF may be associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, with the target of involvement being the heart. Brain-heart interactions may result from an increased systemic and cerebral angiotensin II signaling since plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites causing increased contractility of the heart, as an adaptation, during chronic HF. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM) and area postrema (AP) via neuregulin-brain natriuretic peptide release from these sites which influences the function of cardiomyocytes and the heart. We propose that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. Experimental studies indicate that administration of an angiotensin receptor blocker by injection into the AP activates the sympatho-inhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity which has a beneficial effect on cardiomyocyte function. Angiotensin II also elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings in chronic HF resulting in an increase in sympathetic nerve activity. A rise in circulating angiotensin II during chronic HF may increase the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in cardiomyocyte dysfunction and worsening of HF. Conclusion. Brain-heart interactions and damage to the circadian system with increased circulating angiotensin II signaling may directly act on the brain via the subfornical organ and the AP to increase sympathetic outflow and worsening of neurohumoral adaptations leading to chronic HF. © 2016 Nova Science Publishers, Inc