A Study on Potential Sources of Perineuronal Net-Associated Sema3A in Cerebellar Nuclei Reveals Toxicity of Non-Invasive AAV-Mediated Cre Expression in the Central Nervous System.

Semaphorin 3A (Sema3A) is an axon guidance molecule, which is also abundant in the adult central nervous system (CNS), particularly in perineuronal nets (PNNs). PNNs are extracellular matrix structures that restrict plasticity. The cellular sources of Sema3A in PNNs are unknown.

Impact of Intrauterine Insults on Fetal and Postnatal Cerebellar Development in Humans and Rodents.

Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate during development but one of the last to achieve maturity.

Clinical Performance of an Extended Range of Vision Intraocular Lens After LASIK.

Purpose: To evaluate the clinical and patient-reported outcomes (PROMs) of cataract surgery with implantation of a wavefront-shaping extended depth of focus (EDOF) intraocular lens (IOL) in eyes with previous laser in situ keratomileusis (LASIK) for myopia correction.

Methods: This prospective observational study enrolled 50 eyes with previous LASIK from 25 patients (age: 46 to 70 years) who underwent cataract surgery with implantation of the AcrySof IQ Vivity IOL (Alcon Laboratories, Inc). Visual and refractive outcomes were evaluated during a 3-month follow-up.

Myelofibrosis and allogeneic transplantation: critical points and challenges.

New available drugs allow better control of systemic symptoms associated with myelofibrosis (MF) and splenomegaly but they do not modify the natural history of progressive and poor prognosis disease. Thus, hematopoietic stem cell transplantation (HSCT) is still considered the only available curative treatment for patients with MF. Despite the increasing number of procedures worldwide in recent years, HSCT for MF patients remains challenging.

A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion.

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions.

Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration.

Nicotinamide riboside kinases (NRKs) control the conversion of dietary Nicotinamide Riboside (NR) to NAD, but little is known about their contribution to endogenous NAD turnover and muscle plasticity during skeletal muscle growth and remodeling. Using NRK1/2 double KO (NRKdKO) mice, we investigated the influence of NRKs on NAD metabolism and muscle homeostasis, and on the response to neurogenic muscle atrophy and regeneration following muscle injury. Muscles from NRKdKO animals have altered nicotinamide (NAM) salvage and a decrease in mitochondrial content.

A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD metabolism.

Nicotinamide riboside (NR) is a form of vitamin B and is one of the most studied compounds for the restoration of cellular NAD levels demonstrating clinical potential in many metabolic and age-related disorders. Despite its wide commercial availability as a powerful nutraceutical, our understanding of NR uptake by different cells and tissues is greatly limited by the lack of noninvasive in vivo imaging tools limiting its clinical translation. Here, we report the development and validation of a bioluminescent NR uptake probe (BiNR) for non-invasive longitudinal imaging of NR uptake both in vitro and in vivo.

Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic β-cell failure.

Objective: Disturbances in NAD metabolism have been described as a hallmark for multiple metabolic and age-related diseases, including type 2 diabetes. While alterations in pancreatic β-cell function are critical determinants of whole-body glucose homeostasis, the role of NAD metabolism in the endocrine pancreas remains poorly explored. Here, we aimed to evaluate the role of nicotinamide riboside (NR) metabolism in maintaining NAD levels and pancreatic β-cell function in pathophysiological conditions.

Interpreting thoughts during sleep.

Rapid eye movements during sleep are a readout of thoughts during mouse dreams.

Balancing NAD deficits with nicotinamide riboside: therapeutic possibilities and limitations.

Alterations in cellular nicotinamide adenine dinucleotide (NAD) levels have been observed in multiple lifestyle and age-related medical conditions. This has led to the hypothesis that dietary supplementation with NAD precursors, or vitamin B3s, could exert health benefits. Among the different molecules that can act as NAD precursors, Nicotinamide Riboside (NR) has gained most attention due to its success in alleviating and treating disease conditions at the pre-clinical level.

NAD Precursors: A Questionable Redundancy.

The last decade has seen a strong proliferation of therapeutic strategies for the treatment of metabolic and age-related diseases based on increasing cellular NAD bioavailability. Among them, the dietary supplementation with NAD precursors-classically known as vitamin B3-has received most of the attention. Multiple molecules can act as NAD precursors through independent biosynthetic routes.

Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD by Generating Dihydronicotinamide Riboside.

Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD precursors influence intracellular NAD levels.

Activity of Cerebellar Nuclei Neurons Correlates with ZebrinII Identity of Their Purkinje Cell Afferents.

Purkinje cells (PCs) in the cerebellar cortex can be divided into at least two main subpopulations: one subpopulation that prominently expresses ZebrinII (Z+), and shows a relatively low simple spike firing rate, and another that hardly expresses ZebrinII (Z-) and shows higher baseline firing rates. Likewise, the complex spike responses of PCs, which are evoked by climbing fiber inputs and thus reflect the activity of the inferior olive (IO), show the same dichotomy. However, it is not known whether the target neurons of PCs in the cerebellar nuclei (CN) maintain this bimodal distribution.

A Method to Monitor the NAD Metabolome-From Mechanistic to Clinical Applications.

Nicotinamide adenine dinucleotide (NAD) and its reduced form (NADH) are coenzymes employed in hundreds of metabolic reactions. NAD also serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and ADP-ribosyl cyclases. Given the pivotal role of NAD(H) in health and disease, studying NAD metabolism has become essential to monitor genetic- and/or drug-induced perturbations related to metabolic status and diseases (such as ageing, cancer or obesity), and its possible therapies.

Crosstalk between Drp1 phosphorylation sites during mitochondrial remodeling and their impact on metabolic adaptation.

Mitochondria constantly undergo fusion and fission events, referred as mitochondrial dynamics, which determine mitochondrial architecture and bioenergetics. Cultured cell studies demonstrate that mitochondrial dynamics are acutely regulated by phosphorylation of the mitochondrial fission orchestrator dynamin-related protein 1 (Drp1) at S579 or S600. However, the physiological impact and crosstalk of these phosphorylation sites is poorly understood.

Reduced nicotinamide mononucleotide is a new and potent NAD precursor in mammalian cells and mice.

Nicotinamide adenine dinucleotide (NAD ) homeostasis is constantly compromised due to degradation by NAD -dependent enzymes. NAD replenishment by supplementation with the NAD precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD pool and the need of high doses.

Does mindfulness improve inhibitory control in psychotic disorders? A randomized controlled clinical trial.

Impaired Inhibitory Control (IC) is a core feature of psychotic disorders and is related with impaired social functioning in people experiencing psychosis. Despite research showing the benefits of mindfulness over IC in the general population, no study has assessed its effects on IC in psychoses. The aim of our study was to assess the effectiveness of a mindfulness-based intervention combined with integrated rehabilitation treatment in a sample of people diagnosed of psychotic disorders.

Cerebellar plasticity and associative memories are controlled by perineuronal nets.

Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity.

Sleep deprivation directly following eyeblink-conditioning impairs memory consolidation.

The relation between sleep and different forms of memory formation continues to be a relevant topic in our daily life. Sleep has been found to affect cerebellum-dependent procedural memory formation, but it remains to be elucidated to what extent the level of sleep deprivation directly after motor training also influences our ability to store and retrieve memories. Here, we studied the effect of disturbed sleep in mice during two different time-windows, one covering the first four hours following eyeblink conditioning (EBC) and another window following the next period of four hours.

A reduced form of nicotinamide riboside defines a new path for NAD biosynthesis and acts as an orally bioavailable NAD precursor.

Objective: A decay in intracellular NAD levels is one of the hallmarks of physiological decline in normal tissue functions. Accordingly, dietary supplementation with NAD precursors can prevent, alleviate, or even reverse multiple metabolic complications and age-related disorders in diverse model organisms. Within the constellation of NAD precursors, nicotinamide riboside (NR) has gained attention due to its potent NAD biosynthetic effects in vivo while lacking adverse clinical effects.

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage.

Supplementation with the NAD precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD synthesis in hepatic cells.

Postnatal Development of Functional Projections from Parasubiculum and Presubiculum to Medial Entorhinal Cortex in the Rat.

Neurons in parasubiculum (PaS), presubiculum (PrS), and medial entorhinal cortex (MEC) code for place (grid cells) and head direction. Directional input has been shown to be important for stable grid cell properties in MEC, and PaS and PrS have been postulated to provide this information to MEC. In line with this, head direction cells in those brain areas are present at postnatal day 11 (P11), having directional tuning that stabilizes shortly after eye opening, which is before premature grid cells emerge in MEC at P16.