Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at genetic level, molecular events epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) their associated RNA modifications are important regulators complex physiological pathological processes, including aging, stress responses, inheritance. However, whether altered dementia is not known. Methods We performed...

Emerging small non-coding RNAs (sncRNAs), including tRNA-derived (tsRNAs) and rRNA-derived (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, internal terminal that can interfere with sequencing. We recently developed panoramic RNA display by overcoming modification aborted sequencing (PANDORA-seq), a method enabling comprehensive detection of modified the...

Ca 2+ sparks that control arterial contractility and blood pressure require the lysosomal channel TRPML1.

Cantú syndrome is a multisystem disorder caused by gain-of-function (GOF) mutations in KCNJ8 and ABCC9, the genes encoding pore-forming inward rectifier Kir6.1 regulatory sulfonylurea receptor SUR2B subunits, respectively, of vascular ATP-sensitive K+ channels (KATP). In this study, we investigated changes endothelium mice which -associated Kcnj8 or Abcc9 were knocked-in to endogenous loci. We found that endothelium-dependent dilation was impaired small mesenteric arteries from mice. Loss...

We report here that the neuronal (pro)renin receptor (PRR), a key component of brain renin-angiotensin system (RAS), plays critical role in central regulation high-fat-diet (HFD)-induced metabolic pathophysiology. The PRR is known to mediate formation majority angiotensin (ANG) II, bioactive peptide RAS, nervous and regulate blood pressure cardiovascular function. However, little about function overnutrition-related physiology. Here, we show deletion neurons reduces pressure, neurogenic...

Introduction: Hypoxia-induced dilation of cerebral arteries orchestrated by Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) cation channels on endothelial cells is neuroprotective during ischemic stroke, but it unknown if the channel has a similar impact hemorrhagic stroke. TRPA1 are endogenously activated lipid peroxide metabolites generated reactive oxygen species (ROS). Uncontrolled hypertension, primary risk factor for development associated with increased ROS production...

High salt (sodium) intake leads to the development of hypertension despite fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) contributes elevated sympathetic activity and high blood pressure (BP) rodent models hypertension. However, whether there an increased accumulation CSF humans with chronic not well defined. Here, we investigated [Na+] from normotensive subjects family histories Alzheimer's disease samples...

Overactivation of the renin-angiotensin system (RAS)—a central physiological pathway involved in controlling blood pressure (BP)—leads to hypertension. It is now well recognized that nervous (CNS) has its own local RAS, and majority components are known be expressed brain. In pathological states, (pro)renin receptor (PRR), a novel component brain plays key role formation angiotensin II (Ang II) also mediates Ang II-independent PRR signaling. A recent study reported neuronal activation...

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated play role in glucose lipid metabolism. Here, we test the hypothesis that PRR regulates development diet-induced hepatic steatosis fibrosis. C57Bl/6J mice were fed high-fat diet (HFD) or normal-fat (NFD) with matching calories for 6 weeks. An 8-week methionine choline-deficient (MCD) was used induce...

Glucose homeostasis is achieved via complex interactions between the endocrine pancreas and other peripheral tissues glucoregulatory neurocircuits in brain that remain incompletely defined. Within brain, neurons hypothalamus appear to play a particularly important role. Consistent with this notion, we report evidence (pro)renin receptor (PRR) signaling within subset of tyrosine hydroxylase (TH) located hypothalamic paraventricular nucleus (PVNTH neurons) physiological determinant defended...

Emerging small noncoding RNAs (sncRNAs), including tRNA-derived (tsRNAs) and rRNA-derived (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, internal terminal that can interfere with sequencing. We recently developed panoramic RNA display by overcoming modification aborted sequencing (PANDORA-seq), a method enabling comprehensive detection of modified the...

Hypertension is typically recognized in middle-aged and older adults but often overlooked younger populations.We evaluated a mobile intervention for reducing blood pressure (BP) college-age students 28 days.Students with elevated BP or undiagnosed hypertension were assigned to an control group. All subjects completed baseline questionnaires attended educational session. For days, sent their motivation levels the research team BP-reducing tasks. After all exit interview.We found statistically...

Agouti-related protein (AgRP) neurons, a key neuronal population within the arcuate nucleus (ARC), are known for their pivotal roles in regulating energy- and glucose homeostasis. However, involvement cardiovascular regulation remains poorly understood. Using RNAscope situ hybridization, we found that 95.4% of ARC AgRP neurons express (pro)renin receptor (PRR), component brain renin-angiotensin system is crucial blood pressure (BP) regulation. We therefore hypothesized PRR signaling plays...

The arcuate nucleus of the hypothalamus (ARC) serves as a key regulator cardiovascular and sympathetic regulating center. While neurons in ARC expressing agouti-related peptide (AgRP) are implicated regulation energy- glucose homeostasis, our recent findings show that acute chemogenic activation AgRP reduces blood pressure (BP), whereas inhibition these has opposite effect. Together, observations indicate neuronal activity determinant basal BP suggest tonic may be required to maintain normal...

Chlorisondamine (CSD) has been used to assess the neurogenic contribution blood pressure (BP) and vasomotor sympathetic tone in animal models. It is assumed that reduction BP following CSD administration associated decreases cardiac output (CO) peripheral resistance, reflecting tone, respectively. Surprisingly, this not characterized experimentally mice, despite extensive use of model cardiovascular research. We hypothesize a specific dose can selectively block tone. To test hypothesis, we...

The brain renin-angiotensin system plays important roles in blood pressure and cardiovascular regulation. There are two isoforms of prorenin the brain: classic secreted form (prorenin/sREN) encoded by renin-a, an intracellular (icREN) renin-b. Emerging evidence indicates importance renin-b metabolic However, role endogenous development salt-sensitive hypertension remains undefined. In this study, we test hypothesis that renin-a produced locally contributes to pathogenesis hypertension. Using...

Non‐alcoholic fatty liver disease (NAFLD) represents a diverse array of damage linked to obesity, and metabolic syndrome. The mechanisms the treatment for NAFLD remains lacking; however, recent evidence suggests critical importance (pro)renin receptor (PRR) renin‐angiotensin system (RAS) in lipid metabolism. Our laboratory recently developed novel PRR antagonistic peptide PRO20 that blocks fibrotic signaling activation RAS. We hypothesize antagonism reverses development by preventing RAS...

Background and Purpose: Hypertension is a known risk factor that accelerates leads to cardiovascular disease. While it often recognized in middle-aged older adults, overlooked young adults. The purpose of this study was (1) implement mHealth intervention, the O ptimize B lood Pressure I mprovement ( MOBI LE) college students, aged 18 29 years, with elevated blood pressure (BP); (2) test its feasibility impact on BP reduction (primary outcome) along sodium intake hypertension knowledge...

Tyrosine hydroxylase (TH)-positive neurons in the paraventricular nucleus of hypothalamus (PVN), termed THPVN neurons, have emerged as key metabolic regulators. Recent studies showed that are mostly Gamma-aminobutyric acid (GABA)ergic and/or dopaminergic. However, it is not known if play a role blood glucose regulation. We hypothesize regulators glucose. To test our hypothesis, we used adeno-associated virus serotype 2 (AAV2)-mediated Cre-recombinase driven by rat TH promoter (AAV2-TH-Cre),...

We recently reported that neuron-specific (pro)renin receptor (PRR) deletion reduces blood pressure (BP), fasting glucose (BG) and improves tolerance in high-fat diet (HFD)-treated mice. To investigate underlying mechanisms, we focused on tyrosine hydroxylase (TH) neurons the hypothalamic paraventricular nucleus (TH PVN neurons), a largely GABAergic population expresses PRR projects to autonomic centers important for BP BG regulation. The was ablated specifically TH-positive using Cre-LoxP...

Emerging evidence suggests that epigenetic regulatory mechanisms contribute to the development of hypertension. However, whether there is significance epigenetics on neurogenic hypertension not fully understood. We previously reported an elevation Histone 3 Lysine 4 (H3K4) trimethylation in paraventricular nucleus hypothalamus (PVN). Accordingly, we hypothesize H3K4 histone methyltransferase (HMT) PVN contributes DOCA-salt To test our hypothesis, C57Bl/6J mice were implanted with SHAM or...

Chlorisondamine (CSD), a long‐lasting nicotinic receptor antagonist and ganglionic blocker, has been commonly used to assess the sympathetic vasomotor tone in mice. Both cardiac output peripheral resistance are blood pressure (BP) determinants; however, it is not defined whether BP reduction observed after administration of this agent caused by decrease activity solely vessels (vasomotor tone) or if there contribution from output. The aim study was examine effects CSD BP, identify an...