Does irisin mediate metabolic effects of androgen deficiency? A cross-sectional study in men with chronic spinal cord injury.

Study Design: Retrospective study.

Objectives: To check the hypothesis that irisin could mediate systemic metabolic effects of testosterone in men with chronic spinal cord injury (SCI).

Setting: Spinal Unit of the San Raffaele Institute in Sulmona.

Neuropeptides: The Evergreen Jack-of-All-Trades in Neuronal Circuit Development and Regulation.

Neuropeptides are key modulators of adult neurocircuits, balancing their sensitivity to both excitation and inhibition, and fine-tuning fast neurotransmitter action under physiological conditions. Here, we reason that transient increases in neuropeptide availability and action exist during brain development for synapse maturation, selection, and maintenance. We discuss fundamental concepts of neuropeptide signaling at G protein-coupled receptors (GPCRs), with a particular focus on how signaling at neuropeptide GPCRs could underpin neuronal morphogenesis.

The inactivation of the Niemann Pick C1 cholesterol transporter restricts SARS-CoV-2 entry into host cells by decreasing ACE2 abundance at the plasma membrane.

Background: The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) that is involved in the mobilization of endocytosed cholesterol. Loss-of-function mutations in the NPC1 gene lead to the accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway.

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging.

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in ~ 1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability. Detailed assessment is important to help identify high-risk infants, to help families, and to support appropriate interventions. A wide range of monitoring tools is available to assess changes over time, including urine and blood biomarkers, neurological examination, and electroencephalography.

Molecular insights into the activation mechanism of GPR156 in maintaining auditory function.

The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-G complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus.

Temperature cues are integrated in a flexible circadian neuropeptidergic feedback circuit to remodel sleep-wake patterns in flies.

Organisms detect temperature signals through peripheral neurons, which relay them to central circadian networks to drive adaptive behaviors. Despite recent advances in Drosophila research, how circadian circuits integrate temperature cues with circadian signals to regulate sleep/wake patterns remains unclear. In this study, we used the FlyWire brain electron microscopy connectome to map neuronal connections, identifying lateral posterior neurons LPNs as key nodes for integrating temperature information into the circadian network.

Relaxation-exchange magnetic resonance imaging (REXI): a non-invasive imaging method for evaluating trans-barrier water exchange in the choroid plexus.

Background: The choroid plexus (CP) plays a crucial role in cerebrospinal fluid (CSF) production and brain homeostasis. However, non-invasive imaging techniques to assess its function remain limited. This study was conducted to develop a novel, contrast-agent-free MRI technique, termed relaxation-exchange magnetic resonance imaging (REXI), for evaluating CP-CSF water transport, a potential biomarker of CP function.

Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.

In addition to modulating serotonin transport, selective serotonin reuptake inhibitors (SSRIs) have multiple other mechanisms that may contribute to clinical effects, and some of these latter actions prompt repurposing of SSRIs for non-psychiatric indications. In a recent study of the SSRIs fluvoxamine, fluoxetine and sertraline we found that, unlike the other two SSRIs, sertraline acutely inhibited LTP at a low micromolar concentration through inverse agonism of sigma 1 receptors (S1Rs). In the present studies, we pursued mechanisms contributing to sertraline modulation of LTP in rat hippocampal slices.

A new cancer/testis long noncoding RNA, the OTP-AS1 RNA.

The orthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1.

Alterations of endocannabinoid signaling and microglia reactivity in the retinas of AD-like mice precede the onset of hippocampal β-amyloid plaques.

Extra-cerebral manifestations of Alzheimer's disease (AD) develop in the retina, which is, therefore, considered a "window to the brain". Recent studies demonstrated the dysregulation of the endocannabinoid (eCB) system (ECS) in AD brain. Here, we explored the possible alterations of ECS and the onset of gliosis in the retina of AD-like mice.

Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer's disease: A narrative review.

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on the healthcare system, society, and economy due to the increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques and tau protein neurofibrillary tangles, which are the two main hallmarks of this devastating neurodegenerative disease, have not provided significant results in terms of their neuropathological outcomes nor met the expected clinical end-points.

Anhedonia is associated with a specific depression profile and poor antidepressant response.

Background: Anhedonic features within major depressive disorder (MDD) have been associated with worse course and outcome and may predict nonresponse to treatment. However, a detailed clinical profile of anhedonia in MDD is still lacking.

Materials And Methods: One thousand two hundred ninety-four patients with MDD were selected from the cross-sectional European multicenter Group for the Study of Resistant Depression study.

Enhancing prediction of human traits and behaviors through ensemble learning of traditional and novel resting-state fMRI connectivity analyses.

Recent advances in cognitive neuroscience have focused on using resting-state functional connectivity (RSFC) data from fMRI scans to more accurately predict human traits and behaviors. Traditional approaches generally analyze RSFC by correlating averaged time-series data across regions of interest (ROIs) or networks, which may overlook important spatial signal patterns. To address this limitation, we introduced a novel linear regression technique that estimates RSFC by predicting spatial brain activity patterns in a target ROI from those in a seed ROI.

The periaxonal space as a conduit for cerebrospinal fluid flow to peripheral organs.

Mechanisms controlling the movement of the cerebrospinal fluid (CSF) toward peripheral nerves are poorly characterized. We found that, in addition to the foramina Magendie and Luschka for CSF flow toward the subarachnoid space and glymphatic system, CSF outflow could also occur along periaxonal spaces (termed "PAS pathway") from the spinal cord to peripheral organs, such as the liver and pancreas. When interrogating the latter route, we found that serotonin, acting through 5-HT receptors expressed in ependymocytes that line the central canal, triggered Ca signals to induce polymerization of F-actin, a cytoskeletal protein, to reduce the volume of ependymal cells.