Frontiers in Molecular Neuroscience

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INTRODUCTION: Axonal plasticity is strongly related to neuronal development as well as regeneration. It was recently demonstrated that active mechanical tension, intended as an extrinsic factor, is a valid contribution to the modulation of axonal plasticity. METHODS: In previous publications, our team validated a the "nano-pulling" method used to apply mechanical forces to developing axons of isolated primary neurons using magnetic nanoparticles (MNP) actuated by static magnetic fields...

Protein phosphorylation, a key regulator of cellular processes, plays a central role in brain function and is implicated in neurological disorders. Information on protein phosphorylation is expected to be a clue for understanding various neuropsychiatric disorders and developing therapeutic strategies. Nonetheless, existing databases lack a specific focus on phosphorylation events in the brain, which are crucial for investigating the downstream pathway regulated by neurotransmitters. To overcome the gap, we have developed a web-based database named "Kinase-Associated Neural PHOspho-Signaling (KANPHOS)...

Annually, more than 15 million people worldwide suffer from stroke, a condition linked to high mortality and disability rates. This disease significantly affects daily life, impairing everyday functioning, executive function, and cognition. Moreover, stroke severely restricts patients' ability to perform daily activities, diminishing their overall quality of life. Recent scientific studies have identified cuproptosis, a newly discovered form of cell death, as a key factor in stroke development. However, the role of cuproptosis in stroke remains unclear to researchers...

Here, we investigated the role of the canonical Wnt signaling pathway transcriptional regulators at the neuromuscular junction. Upon applying a denervation paradigm, the transcription levels of Ctnnb1 , Tcf7l1 , Tle1 , Tle2 , Tle3 , and Tle4 were significantly downregulated. A significant decrease in canonical Wnt signaling activity was observed using the denervation paradigm in Axin2-lacZ reporter mice. Alterations in the transcriptional profile of the myogenic lineage in response to agrin (AGRN) suggested that TLE3 and TLE4, family members of groucho transducin-like enhancer of split 3 (TLE3), transcriptional repressors known to antagonize T cell factor/lymphoid enhancer factor (TCF)-mediated target gene activation, could be important regulators of canonical Wnt signaling activity at the postsynapse...

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Radicular pain, a common and complex form of neuropathic pain, presents significant challenges in treatment. Acupuncture, a therapy originating from ancient traditional Chinese medicine and widely utilized for various pain types, including radicular pain, has shown promising outcomes in the management of lumbar radicular pain, cervical radicular pain, and radicular pain due to spinal stenosis. Despite its efficacy, the exact mechanisms through which acupuncture achieves analgesia are not fully elucidated and are the subject of ongoing research...

Axonal extension and retraction are ongoing processes that occur throughout all developmental stages of an organism. The ability of axons to produce mechanical forces internally and respond to externally generated forces is crucial for nervous system development, maintenance, and plasticity. Such axonal mechanobiological phenomena have typically been evaluated in vitro at a single-cell level, but these mechanisms have not been studied when axons are present in a bundled three-dimensional (3D) form like in native tissue...

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal adult-onset neurodegenerative disorders that share clinical, neuropathological and genetic features, which forms part of a multi-system disease spectrum. The pathological process leading to ALS and FTD is the result of the combination of multiple mechanisms that operate within specific populations of neurons and glial cells. The implication of oligodendrocytes has been the subject of a number of studies conducted on patients and related animal models...

Corticotropin-releasing hormone (CRH) neurons play an important role in the regulation of neuroendocrine responses to stress. The excitability of CRH neurons is regulated by inhibitory GABAergic inputs. However, it is unclear when GABAergic regulation of CRH neurons is established during fetal brain development. Furthermore, the exact progression of the developmental shift of GABA action from depolarization to hyperpolarization remains unelucidated. Considering the importance of CRH neuron function in subsequent hypothalamic-pituitary-adrenal (HPA) axis regulation during this critical phase of development, we investigated the ontogeny of GABAergic inputs to CRH neurons and consequent development of chloride homeostasis...

A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch ( APOE3Ch ) displayed extreme resistance to Alzheimer's disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch , we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation...

The prevailing model behind synapse development and specificity is that a multitude of adhesion molecules engage in transsynaptic interactions to induce pre- and postsynaptic assembly. How these extracellular interactions translate into intracellular signal transduction for synaptic assembly remains unclear. Here, we focus on a synapse organizing complex formed by immunoglobulin superfamily member 21 (IgSF21) and neurexin2α (Nrxn2α) that regulates GABAergic synapse development in the mouse brain...

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Inositol polyphosphate 5-phosphatase K (INPP5K), also known as SKIP (skeletal muscle and kidney-enriched inositol phosphatase), is a cytoplasmic enzyme with 5-phosphatase activity toward phosphoinositides (PIs). Mutations in INPP5K are associated with autosomal recessive congenital muscular dystrophy with cataracts and intellectual disability (MDCCAID). Notably, muscular dystrophy is characterized by the hypoglycosylation of dystroglycan. Thus, far, the underlying mechanisms are only partially understood. In this study, we show that INPP5K expression increases during brain development...

INTRODUCTION: Cumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC...

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling...

INTRODUCTION: Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences. METHODS: Working with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020...

The zebrafish ( Danio rerio ) is increasingly used in neuroscience research. Zebrafish are relatively easy to maintain, and their high fecundity makes them suitable for high-throughput experiments. Their small, transparent embryos and larvae allow for easy microscopic imaging of the developing brain. Zebrafish also share a high degree of genetic similarity with humans, and are amenable to genetic manipulation techniques, such as gene knockdown, knockout, or knock-in, which allows researchers to study the role of specific genes relevant to human brain development, function, and disease...

Exosomes, vesicular structures originating from cells, participate in the conveyance of proteins and nucleic acids. Presently, the centrality of epigenetic modifications in neurological disorders is widely acknowledged. Exosomes exert influence over various epigenetic phenomena, thereby modulating post-transcriptional regulatory processes contingent upon their constituent makeup. Consequently, the heightened attention directed toward exosomes as instigators of epigenetic alterations has burgeoned in recent years...

The nucleus accumbens (NAc) and the ventral tegmental area (VTA) are integral brain regions involved in reward processing and motivation, including responses to drugs of abuse. Previously, we have demonstrated that activation of NAc-VTA afferents during the acquisition of cocaine conditioned place preference (CPP) reduces the rewarding properties of cocaine and diminished the activity of VTA dopamine neurons. In the current study, we examined the impact of enhancing these inhibitory inputs on molecular changes and neurotransmission associated with cocaine exposure...