New Insights Into the Role of Inflammation in the Brain in Heart Failure.

Heart failure is a growing medical problem. Although the underlying aetiology of heart failure differs according to the phenotype, there are some common characteristics observed in patients with heart failure. These include an increased sympathetic nerve activity, an activated renin-angiotensin system, and inflammation.

The Enigma of the Adrenarche: Identifying the Early Life Mechanisms and Possible Role in Postnatal Brain Development.

Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[S] in postnatal development remain elusive. Here, we draw attention to this pre-pubertal surge from the adrenal gland-the adrenarche-and discuss whether this is the result of intra-adrenal gene expression specifically affecting the zona reticularis (ZR), if the ZR is influenced by the hypothalamic-pituitary axis, and the possible role of spino-sympathetic innervation in prompting increased ZR activity.

Cardiovascular and Metabolic Crosstalk in the Brain: Leptin and Resistin.

Leptin and resistin are cytokines whose plasma levels correlate with adiposity. Leptin is a hormone synthesised and released from adipocytes and can be transported into the brain. Resistin is produced in adipocytes in rodents and in macrophages in humans, particularly macrophages that have infiltrated adipose tissue.

Students from a large Australian university use Twitter to identify difficult course concepts to review during face-to-face lectorial sessions.

Engaging undergraduate students in large classes is a constant challenge for many lecturers, as student participation and engagement can be limited. This is a concern since there is a positive correlation between increased engagement and student success. The lack of student feedback on content delivery prevents lecturers from identifying topics that would benefit students if reviewed.

The Carotid Body a Common Denominator for Cardiovascular and Metabolic Dysfunction?

The carotid body is a highly vascularized organ designed to monitor oxygen levels. Reducing oxygen levels in blood results in increased activity of the carotid body cells and reflex increases in sympathetic nerve activity. A key contributor to elevated sympathetic nerve activity in neurogenic forms of hypertension is enhanced peripheral chemoreceptor activity.

Central Administration of Insulin Combined With Resistin Reduces Renal Sympathetic Nerve Activity in Rats Fed a High Fat Diet.

Insulin receptors are widely distributed in the central nervous system and their activation by insulin elicits renal sympatho-excitatory effects. Resistin, an adipokine, promotes resistance to the metabolic effects of insulin. Resistin also induces increases in renal sympathetic nerve activity (RSNA) by acting in the brain, but whether it can influence insulin's actions on RSNA is unknown.

A tale of two steroids: The importance of the androgens DHEA and DHEAS for early neurodevelopment.

DHEA and DHEAS are neuroactive neurosteroids that interact with several major receptor systems in the brain, including sigma (σ), glutamate, and GABA-A receptors. It has been recognized as early as 1952, that the loss of DHEA/DHEAS in adult life is associated with neuropsychiatric disorders (eg schizophrenia, depression). However, the mechanistic role for DHEA/DHEAS in any of these domains remains speculative, not the least because the presence of these androgens in the adrenal gland and brain is largely confined to humans and only some non-human primates.

DHEA in Prenatal and Postnatal Life: Implications for Brain and Behavior.

Dehydroepiandrosterone (DHEA) and its sulfated congener (DHEAS) are the principal C steroid produced by the adrenal gland in many mammals, including humans. It is secreted in high concentrations during fetal life, but synthesis decreases after birth until, in humans and some other primates, there is a prepubertal surge of DHEA production by the adrenal gland-a phenomenon known as adrenarche. There remains considerable uncertainty about the physiological role of DHEA and DHEAS.

High Fat Diet Decreases Neuronal Activation in the Brain Induced by Resistin and Leptin.

Resistin and leptin are adipokines which act in the brain to regulate metabolic and cardiovascular functions which in some instances are similar, suggesting activation of some common brain pathways. High-fat feeding can reduce the number of activated neurons observed following the central administration of leptin in animals, but the effects on resistin are unknown. The present work compared the distribution of neurons in the brain that are activated by centrally administered resistin, or leptin alone, and, in combination, in rats fed a high fat (HFD) compared to a normal chow diet (ND).

Central Administration of Insulin and Leptin Together Enhance Renal Sympathetic Nerve Activity and Fos Production in the Arcuate Nucleus.

There is considerable interest in the central actions of insulin and leptin. Both induce sympatho-excitation. This study (i) investigated whether centrally administered leptin and insulin together elicits greater increases in renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) than when given alone, and (ii) quantified the number of activated neurons in brain regions influencing SNA, to identify potential central sites of interaction.

Central leptin and resistin combined elicit enhanced central effects on renal sympathetic nerve activity.

What is the central question of this study? Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. We also used Fos protein to quantify the number of activated neurons in the brain.

Resistin, an Adipokine with Non-Generalized Actions on Sympathetic Nerve Activity.

The World Health Organization has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs.

Attenuation of microglial and neuronal activation in the brain by ICV minocycline following myocardial infarction.

Following myocardial infarction, microglia, the immune cells in the central nervous system, become activated in the hypothalamic paraventricular nucleus (PVN) suggesting inflammation in this nucleus. Little is known about other brain nuclei. In the present study, we investigated whether the rostral ventrolateral medulla (RVLM), the nucleus tractus solitarius (NTS) and the periaqueductal grey (PAG), regions known to have important cardiovascular regulatory functions, also show increased microglial activation and whether this coincides with increased neuronal activity.

Effect of type 1 diabetes on the production and vasoactivity of hydrogen sulfide in rat middle cerebral arteries.

Hydrogen sulfide (H2S) is produced endogenously in vascular tissue and has both vasoregulation and antioxidant effects. This study examines the effect of diabetes-induced oxidative stress on H2S production and function in rat middle cerebral arteries. Diabetes was induced in rats with streptozotocin (50 mg/kg, i.

ERK1/2 in the brain mediates the effects of central resistin on reducing thermogenesis in brown adipose tissue.

We investigated the role of ERK1/2 in the brain on the effects of centrally administered resistin on thermogenesis. Resistin (7 μg) into anaesthetized rats significantly decreased brown adipose tissue temperature by 1.0 ± 0.

A natural variant of obestatin, Q90L, inhibits ghrelin's action on food intake and GH secretion and targets NPY and GHRH neurons in mice.

Background: Ghrelin and obestatin are two gut-derived peptides originating from the same ghrelin/obestatin prepropeptide gene (GHRL). While ghrelin stimulates growth hormone (GH) secretion and food intake and inhibits γ-aminobutyric-acid synaptic transmission onto GHRH (Growth Hormone Releasing Hormone) neurons, obestatin blocks these effects. In Humans, GHRL gene polymorphisms have been associated with pathologies linked to an unbalanced energy homeostasis.

Effect of western and high fat diets on memory and cholinergic measures in the rat.

Recent evidence shows an association between obesity and cognitive decline. The present study aimed to determine whether a very high fat (60%) or western diet can affect working or spatial memory in rats and whether the diet-induced cognitive impairment is linked to the level of acetylcholine in the brain. Three groups of male Long Evans rats were fed either chow, western diet (21% fat, 0.

Sustained activation of microglia in the hypothalamic PVN following myocardial infarction.

Microglia are the immune cells in the central nervous system and can produce cytokines when they are activated by an insult or injury. In the present study, we investigated in detail the time frame of the activation of microglia in the hypothalamic paraventricular nucleus (PVN) following myocardial infarction in rats. Morphological changes and immunohistochemistry to detect CD11b (clone OX-42) were used to identify activated microglia.

Hydrogen Sulfide in the RVLM and PVN has No Effect on Cardiovascular Regulation.

Hydrogen sulfide (H(2)S) is now recognized as an important signaling molecule and has been shown to have vasodilator and cardio-protectant effects. More recently it has been suggested that H(2)S may also act within the brain to reduce blood pressure (BP). In the present study we have demonstrated the presence of the H(2)S-producing enzyme, cystathionine-β-synthase (CBS) in the rostral ventrolateral medulla (RVLM), and the hypothalamic paraventricular nucleus (PVN), brain regions with key cardiovascular regulatory functions.

AT1 receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats.

Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia.

Microglia: activation in acute and chronic inflammatory states and in response to cardiovascular dysfunction.

Microglia are the resident immune cells in the central nervous system and are constantly monitoring their environment. After an insult, they are activated and secrete both pro- and anti-inflammatory mediators. Thus, they can have both detrimental and protective actions.

Inhibition of nitric oxide synthase in the paraventricular nucleus prevents the hyperthermia-induced reduction of mesenteric blood flow in rats.

Increasing body core temperature reflexly decreases mesenteric blood flow (MBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. Nitric oxide (NO) is involved in temperature regulation and is concentrated within the PVN. The present study investigated whether NO in the PVN contributes to the cardiovascular responses elicited by hyperthermia.

Microglia activation in the hypothalamic PVN following myocardial infarction.

Following a myocardial infarction (MI), inflammatory cytokines are elevated in the brain, as well as in plasma, indicating that inflammation is occurring in the brain in addition to the periphery. Microglia are the immune cells in the central nervous system and can produce cytokines when they are activated by an insult or injury. In the present study, we investigated whether MI in rats induces activation of microglia in the brain.

Role of the hypothalamic PVN in the regulation of renal sympathetic nerve activity and blood flow during hyperthermia and in heart failure.

The hypothalamic paraventricular nucleus is a key integrative area in the brain involved in influencing sympathetic nerve activity and in the release of hormones or releasing factors that contribute to regulating body fluid homeostasis and endocrine function. The endocrine and hormonal regulatory function of the paraventricular nucleus is well studied, but the regulation of sympathetic nerve activity and blood flow by this region is less clear. Here we review the critical role of the paraventricular nucleus in regulating renal blood blow during hyperthermia and the evidence pointing to an important pathophysiological role of the paraventricular nucleus in the elevated renal sympathetic nerve activity that is a characteristic of heart failure.