Yu-Hong Jing

Itching is an unpleasant sensory experience that induces the desire to scratch and is clinically divided into histamine‐dependent and non‐dependent types, with the former being the main clinical type. Its pathogenesis mainly involves mast cell degranulation due to various factors, releasing histamine and causing itching. Histamine, a classical pruritogen, is mainly associated with acute pruritus and is the main endogenous pruritic agent responsible for pruritus in patients with allergic skin diseases after exposure to allergens. In recent years, significant progress has been made in understanding the neurocircuits of histamine‐dependent itch from the periphery to the central nervous system. This review focuses on the neurocircuits of histamine‐dependent itch, summarizes the major recent advances in this field, and explores the clinical diagnosis and therapy of histamine‐dependent pruritus based on basic neuroscience findings. By delving into the mechanisms of histamine in the generation, transmission, and processing of itch sensation, this article provides a better entry point and theoretical basis for the treatment of pruritus, especially histamine‐related pruritus, and helps to develop more effective anti‐pruritic drugs in the future to improve patients' quality of life.

Background: The retina, part of the central nervous system, reflects brain pathology. In Alzheimer's disease (AD), it shows changes like amyloid beta (Aβ) accumulation and vascular alterations. Pericytes modulate the glymphatic system, crucial for Aβ clearance, but their role in the ocular glymphatic system is unclear. This study explores pericytes' impact on the glymphatic system and AD‐related retinal pathology. Methods: APP/PS1 mice, a model of progressive Aβ deposition, were crossed with Pdgfr‐β ^+/− mice, which exhibit pericyte dysfunction due to haploinsufficiency of platelet‐derived growth factor receptor β (Pdgfr‐β), generating four littermate genotypes: wild type, Pdgfr‐β ^+/− , APP/PS1 and APP/PS1:Pdgfr‐β ^+/− . Retinal pericytes were assessed by PDGFR‐β and NG 2 labelling, vascular complexity by OCTA and CD31 immunostaining and glymphatic‐related regulation by laminin‐211 and perivascular aquaporin‐4 (AQP‐4) expression. Retinal Aβ and p‐Tau pathology was evaluated by immunofluorescence. Retinal Aβ clearance was assessed in wild type and Pdgfr‐β ^+/− mice using intravitreal FAM–Aβ (1–42) injection followed by quantification of tracer efflux along the optic nerve to the deep cervical lymph nodes. Results: Pdgfr‐β knockdown exacerbated retinal pericyte loss, leading to reduced laminin‐211 expression, disrupted perivascular AQP‐4 polarisation and impaired ocular glymphatic Aβ clearance. Consequently, this disruption is associated with increased Aβ and p‐Tau pathology, reduced vascular complexity and thinning of the retinal layers in APP/PS1 mice. Conclusions: The loss of retinal pericytes is one of the major factors in retinal pathology associated with AD. It exacerbates Aβ and p‐Tau pathology and causes retinal vascular and structural damage by affecting the function of the ocular glymphatic system.

In recent years, the scientific community has increasingly delved into the study of the interaction between the nervous system and tumors, revealing that the nervous system not only regulates bodily functions under physiological conditions, but also assumes a vital part in the emergence and progression of tumors. Research has demonstrated that the extensive neural network directly regulates tumor progression and can influence tumors by modulating the tumor microenvironment and immune system. Moreover, tumors induce neural networks to provide favorable conditions for their proliferation and metastasis. In the above process, neurotransmitters play a vital role. They directly act or bind to their receptor, activating various classical signaling pathways, among which are PI3K/AKT, MEK/ERK, and WNT/β-catenin, to facilitate tumor advancement. Therefore, this study systematically reviews the regulatory mechanisms of neurotransmitters and their receptors in the advancement of cancer, along with the utilization of targeted drugs. At the same time, we also analyzed that targeting specific receptor subtypes may produce more significant therapeutic effects in different types of cancer. Additionally, this research further explores the limitations of neurotransmitter-based drugs currently used in clinical cancer treatment. In summary, the field of cancer neuroscience is rapidly advancing, constantly revealing the regulatory effects of neurotransmitters on tumor progression and their specific molecular mechanisms, providing broad application prospects for future clinical therapy.

Background: Amyloid-β (Aβ) and Aβ plaques can disrupt synaptic plasticity, leading to abnormalities in sensory function and cognition in Alzheimer's disease (AD). The whisker sensorimotor system is crucial for tactile perception, providing rodents with spatial and textural features information about their surroundings. Sensory inputs from whiskers have a clear topological localization in the barrel cortex. Objective: Previous studies have suggested that sensory stimulation can effectively ameliorate the pathology of AD mice and improve cognitive performance. However, it remains unknown whether tactile stimulation via whiskers can activate cortical sensory areas, protect synaptic structure and function. Methods: Here, we established a whisker deprivation (WD) model in the 5×FAD mouse. Results: We found that WD aggravated the deposition of Aβ ₁₋₄₂ , 6E10 and fibrotic Aβ in the cortex, hippocampus and thalamus. Simultaneously, changes in dendritic morphology were consistent with the decreased pCreb levels in the hippocampal dentate gyrus region. WD also reduced axonal projections from layer L4/L5a to L2/3 in the barrel cortex, as well as projections from the entorhinal cortex to the DG, which may disrupt the integration of information in cortical functional columns and weaken the efficiency of information transmission. Additionally, we observed sex differences in effects of WD on AD pathology in 5×FAD mice, with female mice being more sensitive to WD treatment. Ultimately, WD impaired working memory, spatial memory and social behavior in 5×FAD mice. Conclusions: Our study suggested that WD exacerbated the progression of AD pathology in 5×FAD mice, which implicated with Aβ aggravation and synaptic dysfunction.

Alzheimer's disease (AD) is influenced by genetic and environmental factors. Previous studies showed that enriched environments improved memory and reduced amyloid plaques in AD mice, but the underlying mechanisms remain unclear. This study investigated the effects and mechanisms of enriched environments on AD pathology and cognitive function in aged APP/PS1 mice. Male APP/PS1 mice (15 months old) and wild‐type littermates were divided into four groups: WT/SE, WT/EE, Tg/SE, and Tg/EE. Mice in EE groups were subjected to intervention with enriched environment for a period of 5 months. Results showed that enriched environments preserved cognitive function, reduced Aβ and p‐Tau aggregation, and mitigated microglial inflammation (Tlr‐4, NF‐κB, iNOS). They also decreased C1q expression and slowed dendritic spine loss in hippocampal granule cells of APP/PS1 mice. These findings suggest that enriched environments can slow AD progression by regulating microglial inflammation and maintaining neuronal integrity, particularly in hippocampal dendritic spines.

Chronic social stress (CSS) is a significant public health challenge that negatively impacts behavior and immune function through brain‐spleen interactions. Oxytocin (OT), a neuropeptide critical for social behavior and immune regulation, is upregulated during CSS, though its underlying mechanisms remain unclear. This study investigates the role of OT in splenic immune modulation using a murine model of CSS. Behavioral evaluations, serum oxytocin quantification, and splenic immunophenotypic analysis were performed. Splenic denervation confirmed OT’s neuromodulatory role, whereas OTR antagonism revealed its endocrine function. CSS‐induced OT elevation was associated with immunosuppression, characterized by increased Foxp3⁺ regulatory T cells and reduced CD4⁺ T and CD19⁺ B cells. OT also modulated macrophage polarization, inhibiting M1‐like (pro‐inflammatory) and enhancing M2‐like (anti‐inflammatory) phenotypes. Denervation or pharmacological blockade of OT signaling partly reversed CSS‐induced splenic immunosuppression but adversely affected survival in CSS‐exposed mice. Additionally, denervation or OTR antagonism reduced the mice's response to social defeat, as shown by decreased social avoidance behavior. These findings suggest that OT‐mediated immunosuppression likely represents a compensatory mechanism in response to chronic social stress. Targeting the OT–immune axis could offer innovative therapeutic approaches for stress‐associated disorders by restoring immune homeostasis while maintaining behavioral integrity.