Search Results (754)

The hypothalamus–pituitary–ovarian (HPO) axis orchestrates reproductive functions through intricate neuroendocrine crosstalk. Here, we integrated single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) to decode the cellular heterogeneity and intercellular communication networks in the reproductive systems of pregnant Mongolian cattle. We retained a total of 6161 high-quality nuclei from the hypothalamus, 14,715 nuclei from the pituitary, and 26,072 nuclei from the ovary, providing a comprehensive cellular atlas across the HPO axis. In the hypothalamus, neurons exhibited synaptic and neuroendocrine specialization, with glutamatergic subtype Glut4 serving as a TGFβ signaling hub to regulate pituitary feedback, while GABAergic GABA1 dominated PRL signaling, likely adapting maternal behavior. Pituitary stem cells dynamically replenished endocrine populations via TGFβ, and lactotrophs formed a PRL–PRLR paracrine network with stem cells, synergizing mammary development. Ovarian luteal cells exhibited steroidogenic specialization and microenvironmental synergy: endothelial cells coregulated TGFβ-driven angiogenesis and immune tolerance, while luteal–stromal PRL–PRLR interactions amplified progesterone synthesis and nutrient support. Granulosa cells (GCs) displayed spatial-functional stratification, with steroidogenic GCs persisting across pseudotime as luteinization precursors, while atretic GCs underwent apoptosis. Spatial mapping revealed GCs’ annular follicular distribution, mediating oocyte–somatic crosstalk, and luteal–endothelial colocalization supporting vascularization. This study unveils pregnancy-specific HPO axis regulation, emphasizing multi-organ crosstalk through TGFβ/PRL pathways and stem cell-driven plasticity, offering insights into reproductive homeostasis and pathologies. Full article

The ability of the neuropeptide oxytocin to affect glial cell function is receiving increasing attention. We previously reported that oxytocin at a low nanomolar concentration could inhibit both astrocytic Ca²⁺ signals and glutamate release. Here, we investigate the ability of oxytocin receptors to couple both inhibitory and stimulatory pathways in astrocytes, as already reported in neurons. We assessed the effects of oxytocin at concentrations ranging from low to high in the nanomolar range on intracellular Ca²⁺ signals and on the glutamate release in astrocyte processes freshly prepared from the striatum of adult rats. Our main findings are as follows: oxytocin could induce dual responses in astrocyte processes, namely the inhibition and facilitation of both Ca²⁺ signals and glutamate release; the inhibitory and the facilitatory response appeared dependent on activation of the G_i and the G_q pathway, respectively; both inhibitory and facilitatory responses were evoked at the same nanomolar oxytocin concentrations; and the biased agonists atosiban and carbetocin could duplicate oxytocin’s inhibitory and facilitatory response, respectively. In conclusion, due to the coupling of striatal astrocytic oxytocin receptors to different transduction pathways and the dual effects on Ca²⁺ signals and glutamate release, oxytocin could also play a crucial role in neuron–astrocyte bi-directional communication through a subtle regulation of striatal glutamatergic synapses. Therefore, astrocytic oxytocin receptors may offer pharmacological targets to regulate glutamatergic striatal transmission, which is potentially useful in neuropsychiatric disorders and in neurodegenerative diseases. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article

This article first constructs a multi-layer deep learning neural network to help understand the structural characteristics of communication data, thereby learning complex functions and obtaining the predicted network values. At the same time, signal transmission is achieved through the interconnection of neurons, the representation performance of which is enhanced through activation functions; this completes the modeling of IoT communication models. Then, we use the analytic hierarchy process to construct a deep learning autoencoder and extract the feature elements of network communication reliability parameters. Finally, we use the obtained total reliability indicators as features for automatic coding and evaluate the mapping relationship between indicators. The results show that the success rates of handovers in deep leaning-based IoT communication based are all greater than 99.6%. The predicted transmission rate can reach a maximum of 99.5%, achieving error free communication output and improving fidelity. Full article

This perspective paper presents a first-person account of life with motor neurone disease (MND). Through the lens of lived experience, it explores the complex and often prolonged diagnostic journey, shaped in part by the protective grip of denial. This paper then delves into the emotional impact of MND on the individual and their close relationships, capturing the strain on identity and family dynamics. It also highlights the vital role of the multidisciplinary team in providing support throughout the journey. A central focus of the paper is the personal journey of voice banking. It reflects on the restorative experience of reclaiming a pre-disease voice through tools such as ElevenLabs^TM. This narrative underscores the critical importance of early intervention and timely access to voice banking, positioning voice not only as a tool for communication but also as a powerful anchor of identity, dignity, and agency. The paper concludes by highlighting key systemic gaps in MND care. It calls for earlier referral to speech pathology, earlier access to voice banking, access to psychological support from the time of diagnosis, and better integration between research and clinical care. Full article

The gut–brain axis (GBA) represents a complex bidirectional communication network that links the gut microbiota (GM) and the central nervous system (CNS). Recent research has revealed that neurosteroids (NSs) play crucial roles in modulating neuroinflammatory responses and promoting neuroprotection. Meanwhile, GM alterations have been associated with various neuroinflammatory and neurodegenerative conditions, such as multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis. This review aims to provide a comprehensive overview of the intricate interactions between NS, GM, and neuroinflammation. We discuss how NS and metabolites can influence neuroinflammatory pathways through immune, metabolic, and neuronal mechanisms. Additionally, we explore how GM modulation can impact neurosteroidogenesis, highlighting potential therapeutic strategies that include probiotics, neuroactive metabolites, and targeted interventions. Understanding these interactions may pave the way for innovative treatment approaches for neuroinflammatory and neurodegenerative diseases, promoting a more integrated view of brain health and disease management. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood–brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction and working memory impairment, with early hippocampal damage being a prominent feature. Transcranial magneto-acoustic stimulation (TMAS) has been shown to target specific brain regions for neuroregulation. Methods: This study investigated the effects of TMAS on cognitive function, working memory, and hippocampal CA3 neural rhythms in AD rats by specifically stimulating the hippocampal region. Results: The novel object recognition test and T-maze test were employed to assess behavioral performance, while time-frequency analyses were conducted to evaluate memory-related activity, neural synchronization, and cross-frequency phase-amplitude coupling. TMAS significantly improved cognitive and working memory deficits in AD rats, enhancing long-term memory performance. Additionally, the abnormal energy levels observed in the θ and γ rhythm power spectra of the CA3 region were markedly restored, suggesting the recovery of normal neural function. This improvement was accompanied by a partial resurgence of neural activity, indicating enhanced inter-neuronal communication. Furthermore, the previously damaged coupling between the θ-fast γ and θ-slow γ rhythms was successfully improved, resulting in a notable enhancement of synchronized activity. Conclusions: These findings suggest that TMAS effectively alleviates cognitive and working memory impairments in AD rats and may provide experimental support for developing new treatments for AD. Full article

The cellular prion protein (PrP^C) is studied in prion diseases, where its misfolded isoform (PrP^Sc) leads to neurodegeneration. PrP^C has also been implicated in several physiological functions. The protein is abundant in the nervous system, and it is critical for cell signaling in cellular communication, where it acts as a scaffold for various signaling molecules. The Reelin signaling pathway, implicated both in Alzheimer’s and prion diseases, engages Dab1, an adaptor protein influencing APP processing and amyloid beta deposition. Here, we show, using Prnp knockout models (Prnp^0/0), that PrP^C modulates Reelin signaling, affecting Dab1 activation and downstream phosphorylation in both neuronal cultures and mouse brains. Notably, Prnp^0/0 mice showed reduced responsiveness to Reelin, associated with altered Dab1 phosphorylation and Fyn kinase activity. Even though no direct interaction between PrP^C and Reelin/ApoER2 was found, Prnp^0/0 neurons showed lower NCAM levels, a well-established PrP^C interactor. Prion infection further disrupted the Reelin signaling pathway, thus downregulating Dab1 and Reelin receptors and altering Reelin processing, like Alzheimer’s disease pathology. These findings emphasize PrP^C indirect role in Dab1 signaling via the NCAM and Fyn pathways, which influence synaptic function and neurodegeneration in prion diseases. Full article

Chronic migraine (CM) is a debilitating neurological disorder, yet the glial-specific mechanisms underlying its pathophysiology in the trigeminal nucleus caudalis (TNC)—a critical hub for craniofacial pain processing—remain poorly understood. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to resolve cell-type-specific transcriptional landscapes in a nitroglycerin (NTG)-induced CM rat model, with a particular focus on microglia and astrocytes. We identified 19 transcriptional clusters representing nine major cell types, among which reactive microglia (NTG-Mic) and astrocytes (NTG-Asts) were markedly expanded. The NTG-Mic displayed a glycolysis-dominant, complement-enriched state, whereas the NTG-Asts exhibited concurrent activation of amino acid transport and cytokine signaling pathways. Pseudotime trajectory analysis revealed bifurcated glial activation paths, with NTG driving both cell types toward terminal reactive states. Intercellular communication inference uncovered suppressed homeostatic interactions (e.g., CSF1-CSF1R) alongside enhanced proinflammatory signaling (e.g., FGF1-FGFR2, PTN-SDC4), particularly affecting neuron–glia and glia–glia crosstalk. Together, these findings define a high-resolution atlas of glial reprogramming in CM, implicating state-specific metabolic–immune transitions and dysregulated glial communication as potential targets for therapeutic intervention. Full article

The gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highlighted the pivotal role of the gut microbiota in modulating this axis, forming the microbiota-gut-brain axis (MGBA). Our review synthesizes current knowledge on the anatomical and functional substrates of gut-brain communication, focusing on interoceptive signaling, the roles of intrinsic primary afferent neurons (IPANs) and enteroendocrine cells (EECs) and the influence of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and indoles. These agents modulate neurotransmission, epithelial barrier function, and neuroimmune interactions. The vagus nerve serves as a primary pathway for afferent sensory signaling from the gut influenced indirectly by the ENS and microbiota. Dysbiosis has been associated with altered gut-brain signaling and implicated in the pathophysiology of disorders ranging from irritable bowel syndrome to mood disorders and neurodegeneration. Microbial modulation of host gene expression via epigenetic mechanisms, including microRNAs, adds another layer of complexity. The gut has a crucial role as an active sensory and signaling organ capable of influencing higher-order brain functions. Understanding the MGBA has significant implications for new therapeutic interventions targeting the microbiome to manage neurogastroenterological and even neuropsychiatric conditions. Full article

Around the same time that 6G networks will be launched, advances in quantum computing could challenge existing cryptographic security. This study provides a new approach for designing a quantum-safe 6G security architecture powered by neurons. The framework uses connected cognitive agents that apply neuro-symbolic learning to respond quickly to any quantum-based security threats that may appear in network slices. Experiments carried out using simulations across various network setups with different threats verify that the presented method improves the detection rate of quantum attacks by 37.8%, uses 29.2% less communication capacity than other methods in the field. This network includes features that strengthen it to resist quantum decryption, while at the same time keeping replies fast enough for 6G. When using specific quantum-inspired techniques, accomplishing tasks requires only 42.5% fewer false alarms compared to other intrusion methods. With this research, people are now better prepared for quantum-protected wireless networks and 6G systems that ensure stability in the future. Full article

Lead (Pb) is a pervasive neurotoxicant with well-documented detrimental effects on the central nervous system, particularly in vulnerable populations such as children. Despite historical recognition of its toxicity, Pb exposure remains a significant public health concern due to its environmental persistence, historical industrial use, and ongoing applications in modern technologies. This review focuses on the mechanisms by which Pb disrupts glutamatergic signaling, a critical pathway for learning, memory, and synaptic plasticity. Pb’s interference with glutamate receptors (ionotropic NMDA and AMPA, as well as metabotropic receptors), transporters (EAATs, VGLUTs, and SNATs), and metabolic pathways (glutamate–glutamine cycle, TCA cycle, and glutathione synthesis) are detailed. By mimicking divalent cations like Ca²⁺ and Zn²⁺, Pb²⁺ disrupts calcium homeostasis, exacerbates excitotoxicity, and induces oxidative stress, ultimately impairing neuronal communication and synaptic function. These molecular disruptions manifest cognitive deficits, behavioral abnormalities, and increased susceptibility to neurodevelopmental and neurodegenerative disorders. Understanding Pb’s impact on glutamatergic neurotransmission offers critical insights into its neurotoxic profile and highlights the importance of addressing its effects on neural function. Full article

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by the pathological accumulation of amyloid-β plaques and tau neurofibrillary tangles, both of which disrupt neuronal communication and function. Emerging evidence highlights the role of extracellular vesicles (EVs) as key mediators of intercellular communication, particularly in the propagation of pathological proteins in AD. Among the regulatory factors influencing EV composition and function, neuraminidase 1 (NEU1), a lysosomal sialidase responsible for desialylating glycoproteins has gained attention for its involvement in EV glycosylation. This review explores the role of NEU1 in modulating EV glycosylation, with particular emphasis on its influence on immune modulation and intracellular trafficking pathways and the subsequent impact on intercellular signaling and neurodegenerative progression. Altered NEU1 activity has been associated with abnormal glycan profiles on EVs, which may facilitate the enhanced spread of amyloid-β and tau proteins across neural networks. By regulating glycosylation, NEU1 influences EV stability, targeting and uptake by recipient cells, primarily through the desialylation of surface glycoproteins and glycolipids, which alters the EV charge, recognition and receptor-mediated interactions. Targeting NEU1 offers a promising therapeutic avenue to restore EV homeostasis and reduces pathological protein dissemination. However, challenges persist in developing selective NEU1 inhibitors and effective delivery methods to the brain. Furthermore, altered EV glycosylation patterns may serve as potential biomarkers for early AD diagnosis and monitoring. Overall, this review highlights the importance of NEU1 in AD pathogenesis and advocates for deeper investigation into its regulatory functions, with the aim of advancing therapeutic strategies and biomarker development for AD and related neurological disabilities. Full article

Oligodendrocyte precursor cells (OPCs) are a dynamic and heterogeneous population of glial cells essential for brain development and myelination. Beyond their well-established role in oligodendrogenesis, emerging evidence suggests that OPCs contribute to synaptic regulation, neuronal communication, and brain plasticity. Recent studies have increasingly implicated OPC dysfunction in the pathophysiology of psychiatric disorders, particularly schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). This narrative review integrates clinical, genetic, transcriptomic, and histological findings to examine the role of OPC alterations in mental illnesses. In SCZ, OPC abnormalities predominantly affect myelination, but recent data also suggest deficits in non-canonical functions, including neuron–OPC communication. Findings in BD largely mirror those in SCZ, implying shared OPC-related mechanisms across these disorders. In contrast, OPC involvement in MDD appears more complex, with evidence supporting both myelination deficits and non-canonical dysfunctions, such as impaired neuro–glial interactions and perineuronal network alterations. The developmental timing of OPC dysfunction may represent a common denominator underlying psychiatric disorders, as early-life stress and neurodevelopmental disturbances have been linked to OPC impairments. Moreover, given the shared developmental origins of OPCs and parvalbumin-positive interneurons, disruptions in their mutual interactions may contribute to broader neural network dysregulation. Despite these insights, the field remains in its infancy. Future studies integrating independent human cohorts with robust preclinical models are needed to clarify the extent of OPC involvement in psychiatric pathophysiology. Understanding OPC dysfunction may reveal novel biomarkers and open new avenues for individualized therapeutic interventions and preventive strategies in mental health. Full article