A route for cerebrospinal fluid flow through leptomeningeal arterial-venous overlaps enables macromolecule and fluid shunting.

The flow of cerebrospinal fluid (CSF) is important for conveying brain-derived macromolecules for signaling and enabling them to be drained from the brain parenchyma. The glymphatic route is the best-characterized means of this CSF flow; however, it does not permit the movement of larger macromolecules. Here, we identify in mice an alternative route whereby intra-CSF-injected macromolecules can traverse from periarterial to perivenous spaces, with transfer occurring at sites of overlap between leptomeningeal perivascular (arteriovenous) spaces dispersed across the surface of the brain's leptomeninges.

Meningeal lymphatics-microglia axis regulates synaptic physiology.

Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks.

Incorporation of Whole or Milled Dry Edible Beans into a High-Fat Diet Improves Bone Structure in Obese Mice.

Background: Pulses, a healthy diet component, have many bone-beneficial nutrients.

Objectives: This study investigated whether incorporation of dried pulses to a high-fat diet improves bone metabolism in obese mice.

Methods: Male C57BL/6 mice at 4-wk-old were randomly assigned to 4 diet groups (n = 22-24/group) for 12 wk: a normal-fat (NF; 4.

An Environmentally Compatible and Less Costly (Greener) Microwave Digestion Method of Bone Samples Using Dilute Nitric Acid for Analysis by ICP-MS.

An environmentally compatible and less costly (greener) analytical method for the digestion of bone meal samples using microwave-assisted dilute nitric acid (HNO) was developed and optimized. The method, employing a mixture of 1 mL concentrated HNO and 4 mL of deionized water, offered a comparable performance to the conventional method using 5 mL of concentrated HNO. The accuracy of the method was validated by using certified reference material NIST 1486 (Bone Meal); percentage recoveries were within ±15% for all eight certified elements.

Endogenous self-peptides guard immune privilege of the central nervous system.

Despite the presence of strategically positioned anatomical barriers designed to protect the central nervous system (CNS), it is not entirely isolated from the immune system. In fact, it remains physically connected to, and can be influenced by, the peripheral immune system. How the CNS retains such responsiveness while maintaining an immunologically unique status remains an outstanding question.

Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats.

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption.

Brain-Engrafted Monocyte-derived Macrophages from Blood and Skull-Bone Marrow Exhibit Distinct Identities from Microglia.

Microglia are thought to originate exclusively from primitive macrophage progenitors in the yolk sac (YS) and to persist throughout life without much contribution from definitive hematopoiesis. Here, using lineage tracing, pharmacological manipulation, and RNA-sequencing, we elucidated the presence and characteristics of monocyte-derived macrophages (MDMs) in the brain parenchyma at baseline and during microglia repopulation, and defined the core transcriptional signatures of brain-engrafted MDMs. Lineage tracing mouse models revealed that MDMs transiently express CD206 during brain engraftment as CD206 microglia precursors in the YS.

Effects of Statin and Annatto-extracted Tocotrienol Supplementation on Glucose Homeostasis, Bone Microstructure, and Gut Microbiota Composition in Obese Mice.

Background/aim: This study examined the effects of tocotrienols (TT) in conjunction with statin on glucose homeostasis, bone microstructure, gut microbiome, and systemic and liver inflammatory markers in obese C57BL/6J mice.

Materials And Methods: Forty male C57BL/6J mice were fed a high-fat diet (HFD) and assigned into four groups in a 2 (no statin vs. 120 mg statin/kg diet)×2 (no TT vs.

Calcium Deficiency Decreases Bone Mass without Affecting Adiposity in Ovariectomized Rats Fed a High-Fat Diet.

Obesity induced by a high-fat (HF) diet increases bone resorption and/or decreases bone formation, resulting in reduced bone mass and strength in various animal models. Studies showed that Ca intake is a modifiable factor for osteoporosis and obesity. This study investigated whether Ca deficiency affects bone structure and adiposity in ovariectomized (OVX) rats fed a HF diet.

Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats.

Rapid and extensive sublesional bone loss after spinal cord injury (SCI) is a difficult medical problem that has been refractory to available interventions except the antiresorptive agent denosumab (DMAB). While DMAB has shown some efficacy in inhibiting bone loss, its concurrent inhibition of bone formation limits its use. Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 is expressed on the cell surface of mature osteoclasts.

Time of day of exercise does not affect the beneficial effect of exercise on bone structure in older female rats.

Circadian clock genes are expressed in bone and biomarkers of bone resorption and formation exhibit diurnal patterns in animals and humans. Disruption of the diurnal rhythms may affect the balance of bone turnover and compromise the beneficial effects of exercise on bone. This study investigated whether the time of day of exercise alters bone metabolism in a rodent model.

Gamma and vega hedging using deep distributional reinforcement learning.

We show how reinforcement learning can be used in conjunction with quantile regression to develop a hedging strategy for a trader responsible for derivatives that arrive stochastically and depend on a single underlying asset. We assume that the trader makes the portfolio delta-neutral at the end of each day by taking a position in the underlying asset. We focus on how trades in options can be used to manage gamma and vega.

Effect of Dietary Geranylgeraniol and Green Tea Polyphenols on Glucose Homeostasis, Bone Turnover Biomarkers, and Bone Microstructure in Obese Mice.

Previously, we demonstrated that the administration of either geranylgeraniol (GGOH) or green tea polyphenols (GTP) improved bone health. This study examined the combined effects of GGOH and GTP on glucose homeostasis in addition to bone remodeling in obese mice. We hypothesized that GGOH and GTP would have an additive or synergistic effect on improving glucose homeostasis and bone remodeling possibly in part via suppression of proinflammatory cytokines.

Increasing Vegetable Intake Decreases Urinary Acidity and Bone Resorption Marker in Overweight and Obese Adults: An 8-Week Randomized Controlled Trial.

Background: Controlled intervention trials are needed to confirm a positive association from epidemiological studies between vegetable consumption and bone health.

Objective: We investigated whether providing vegetables at the Dietary Guidelines for Americans (DGA) recommended amount affects excretion of acid and calcium in urine and bone turnover markers in serum in adults with low vegetable intake.

Methods: In total, 102 adults (19 males and 83 females, age 18-65 y, BMI ≥25 kg/m2) consuming ≤1 serving of vegetables (128 g raw leafy or 64 g cooked vegetables) per d were recruited in a 2-arm, parallel, randomized, controlled, and community-based 8-wk feeding intervention trial.

Beneficial effect of dietary geranylgeraniol on glucose homeostasis and bone microstructure in obese mice is associated with suppression of proinflammation and modification of gut microbiome.

Geranylgeraniol (GGOH) is found in edible oils such as olive, linseed, and sunflower oils, which have favorable metabolic effects. However, it is unknown whether these physiological benefits are mediated through the gut microbiome. Thus, the purpose of this study was to test the hypothesis that GGOH supplementation would improve glucose homeostasis and benefit the bone microstructure in obese mice through suppression of inflammation and modification of gut microbiota composition.

Deficiency of PPARγ in Bone Marrow Stromal Cells Does not Prevent High-Fat Diet-Induced Bone Deterioration in Mice.

Background: Bone marrow osteoblasts and adipocytes are derived from a common mesenchymal stem cell and have a reciprocal relationship. Peroxisome proliferator-activated receptor gamma (PPARγ), a regulator for adipocyte differentiation, may be a potential target for reducing obesity and increasing bone mass.

Objectives: This study tested the hypothesis that bone-specific Pparg conditional knockout (cKO), via deletion of Pparg from bone marrow stromal cells (BMSC) using Osterix 1 (Osx1)-Cre, would prevent high-fat (HF) diet-induced bone deterioration in mice.

Voluntary running of defined distances alters bone microstructure in C57BL/6 mice fed a high-fat diet.

Obesity increases the risk for pathological conditions such as bone loss. On the other hand, physical exercise reduces body adiposity. To test the hypothesis that physical activity improves bone quality, we evaluated voluntary running of defined distances on trabecular and cortical microstructure in mice fed a high-fat diet (HFD).

Salivary Aβ Secretion and Altered Oral Microbiome in Mouse Models of AD.

Background: Beta amyloid (Aβ) peptide containing plaque aggregations in the brain are a hallmark of Alzheimer's Disease (AD). However, Aβ is produced by cell types outside of the brain suggesting that the peptide may serve a broad physiologic purpose.

Objective: Based upon our prior work documenting expression of amyloid β precursor protein (APP) in intestinal epithelium we hypothesized that salivary epithelium might also express APP and be a source of Aβ.

Electrical stimulation of hindlimb skeletal muscle has beneficial effects on sublesional bone in a rat model of spinal cord injury.

Spinal cord injury (SCI) results in marked atrophy of sublesional skeletal muscle and substantial loss of bone. In this study, the effects of prolonged electrical stimulation (ES) and/or testosterone enanthate (TE) on muscle mass and bone formation in a rat model of SCI were tested. Compared to sham-transected animals, a significant reduction of the mass of soleus, plantaris and extensor digitorum longus (EDL) muscles was observed in animals 6 weeks post-SCI.

Osteoprotective effect of green tea polyphenols and annatto-extracted tocotrienol in obese mice is associated with enhanced microbiome vitamin K biosynthetic pathways.

The role of the gut microbiome in bone health has received significant attention in the past decade. We investigated the effects of green tea polyphenols (GTP) and annatto-extracted tocotrienols (AT) on bone properties and gut microbiome in obese mice. Male mice were assigned to a two (no AT vs.

Decreasing the Ratio of Dietary Linoleic to α-Linolenic Acid from 10 to 4 by Changing Only the Former Does Not Prevent Adiposity or Bone Deterioration in Obese Mice.

Background: Linoleic acid (LA; 18:2n-6) has been considered to promote low-grade chronic inflammation and adiposity. Studies show adiposity and inflammation are inversely associated with bone mass.

Objectives: This study tested the hypothesis that decreasing the dietary ratio of LA to α-linolenic acid (ALA, 18:3n-3), while keeping ALA constant, mitigates high-fat diet (HF)-induced adiposity and bone loss.

Deletion of PPARγ in Mesenchymal Lineage Cells Protects Against Aging-Induced Cortical Bone Loss in Mice.

Bone loss in aging is linked with chronic low-grade inflammation and the accumulation of marrowfat in animals and humans. Peroxisome proliferator-activated receptor gamma (PPARγ), an adipogenic regulator, plays key roles in these biological processes. However, studies of the roles of PPARγ in age-related bone loss and inflammation are lacking.