Enhanced multiscale human brain imaging by semi-supervised digital staining and serial sectioning optical coherence tomography.

A major challenge in neuroscience is visualizing the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features but suffers from staining variability, tissue damage, and distortion, which impedes accurate 3D reconstructions. The emerging label-free serial sectioning optical coherence tomography (S-OCT) technique offers uniform 3D imaging capability across samples but has poor histological interpretability despite its sensitivity to cortical features.

Anatomy, histology and ultrastructure of the adult human olfactory peduncle: Blood vessel and corpora amylacea assessment.

The mammalian olfactory system is responsible for processing environmental chemical stimuli and comprises several structures, including the olfactory epithelium, olfactory bulb, olfactory peduncle (OP), and olfactory cortices. Despite the critical role played by the OP in the conduction of olfactory information, it has remained understudied. In this work, optical, confocal, and electron microscopy were employed to examine the anatomy, histology, and ultrastructure of six human OP specimens (ages 37-84 years).

Phosphodiesterase 4D inhibition improves the functional and molecular outcome in a mouse and human model of Charcot Marie Tooth disease 1 A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. It is primarily marked by Schwann cell dedifferentiation and demyelination, leading to motor and sensory deficits. Cyclic adenosine monophosphate (cAMP) is crucial for Schwann cell differentiation and maturation.

Maternal and psychosocial antecedents of anxiety and depression in extremely low gestational age newborns at age 15 years.

Objectives: The prevalence of many psychiatric symptoms, including anxiety and depression, is higher in individuals born extremely preterm (EP) than in term-born individuals during childhood and adolescence. In this prospective study of adolescents born EP, we examined associations between early-life risk factors (prenatal maternal health conditions, socioeconomic and social factors) and anxiety and depression at 15 years of age.

Methods: We included 682 participants (53.

Measuring psychological well-being in a danish pregnancy cohort using the self-reported WHO-5 index.

Background: Reduced well-being and depressive episodes frequently complicate pregnancy and can result in serious adverse outcomes for both mother and infant if left untreated. This study aimed to assess the psychometric validity of the 5-item World Health Organization index (WHO-5), and to evaluate if the WHO-5 index can serve as a proxy for two items of core depressive symptoms from the Major Depression Inventory (MDI), identified as MDI-2. Additionally, the paper aimed to assess well-being and detect risk factors of reduced well-being using the WHO-5 index.

Neuronal segmentation in cephalopod arms.

Prehensile arms are among the most remarkable features of the octopus, but little is known about the neural circuitry controlling arm movements. Here, we report on the cellular and molecular organization of the arm nervous system, focusing on its massive axial nerve cords (ANCs). We found that the ANC is segmented.

Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.

The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age.

Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.

To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.

LCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes.

Unlabelled: LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D.

Material And Methods: 4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control.

Poststroke Translocator Protein Expression Dynamics and Correlations to Chronic Infarction: A -CLINDE-SPECT Study.

Background And Purpose: This study aims to investigate the longitudinal changes in translocator protein (TSPO) following stroke in different brain regions and potential associations with chronic brain infarction.

Methods: Twelve patients underwent SPECT using the TSPO tracer 6-Chloro-2-(4'-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide, as well as structural MRI, at 10, 41, and 128 days (median) after ischemic infarction in the middle cerebral artery. TSPO expression was measured in lesional (MRI lesion and SPECT lesion), connected (pons and ipsilesional thalamus), and nonconnected (ipsilesional cerebellum and contralesional occipital cortex) regions.

Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial).

Introduction: Alcohol use disorder (AUD) is a massive burden for the individual, relatives and society. Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies.

Sepsis-induced NET formation requires MYD88 but is independent of GSDMD and PAD4.

Neutrophils are peripheral blood-circulating leukocytes that play a pivotal role in host defense against bacterial pathogens which upon activation, they release web-like chromatin structures called neutrophil extracellular traps (NETs). Here, we analyzed and compared the importance of myeloid differentiation factor 88 (MYD88), peptidyl arginine deiminase 4 (PAD4), and gasdermin D (GSDMD) for NET formation in vivo following sepsis and neutrophilia challenge. Injection of lipopolysaccharide (LPS)/E.

Environmental enrichment is associated with favorable memory-related functional brain activity patterns in older adults.

Background: In humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13-30 years) and midlife (30-65 years) is associated with better preserved memory-related brain activity patterns in older age.

Methods: In total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated.

Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line.

Additional analyses of stem catarrhine and hominoid dental morphology support Kapi ramnagarensis as a stem hylobatid.

Fossil gibbons are exceedingly rare, with much of the hylobatid fossil record and, consequently, hylobatid evolutionary history remaining unknown. Kapi ramnagarensis was described as a stem hylobatid on the basis of an isolated lower right M from ∼13.0-12.

Molecular and spatial analysis of ganglion cells on retinal flatmounts: diversity, topography, and perivascularity.

Diverse retinal ganglion cells (RGCs) transmit distinct visual features from the eye to the brain. Recent studies have categorized RGCs into 45 types in mice based on transcriptomic profiles, showing strong alignment with morphological and electrophysiological properties. However, little is known about how these types are spatially arranged on the two-dimensional retinal surface-an organization that influences visual encoding-and how their local microenvironments impact development and neurodegenerative responses.

Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

Phenotype Spectrum of TRPM3-Associated Disorders.

Objective: Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.

Methods: We analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22).

A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice.

: The periaqueductal gray (PAG) is a central hub for the regulation of aggression, whereas the circuitry and molecular mechanisms underlying this regulation remain uncharacterized. In this study, we investigate the role of a distinct cell type, -expressing (Tac2) neurons, located in the dorsomedial PAG (dmPAG) and their modulation of aggressive behavior in mice. : We combined activity mapping, Ca recording, chemogenetic and pharmacological manipulation, and a viral-based translating ribosome affinity purification (TRAP) profiling using a mouse resident-intruder model.

Laser-capture microdissection for spatial transcriptomics of immunohistochemically detected neurons.

We developed a versatile 'IHC/LCM-Seq' method for spatial transcriptomics of immunohistochemically detected neurons collected with laser-capture microdissection (LCM). IHC/LCM-Seq uses aluminon and polyvinyl sulfonic acid for inventive RNA-preserving strategies to maintain RNA integrity in free-floating sections of 4% formaldehyde-fixed brains. To validate IHC/LCM-Seq, we first immunostained and harvested striatal cholinergic interneurons with LCM.

Design of Small Non-Peptidic Ligands That Alter Heteromerization between Cannabinoid CB and Serotonin 5HT Receptors.

Activation of cannabinoid CB receptors (CBR) by agonists induces analgesia but also induces cognitive impairment through the heteromer formed between CBR and the serotonin 5HT receptor (5HTR). This side effect poses a serious drawback in the therapeutic use of cannabis for pain alleviation. Peptides designed from the transmembrane helices of CBR, which are predicted to bind 5HTR and alter the stability of the CBR-5HTR heteromer, have been shown to avert CBR agonist-induced cognitive impairment while preserving analgesia.

Sex-dependent efficacy of sphingosine-1-phosphate receptor agonist FTY720 in mitigating Huntington's disease.

Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions.

Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs.

Background: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors.