Androgen deprivation exacerbates AD pathology by promoting the loss of microglia in an age-dependent manner.

AIMS: Microglial cells are integral to the pathogenesis of Alzheimer's disease (AD). The observed sex disparity in AD prevalence, with a notable predominance in women, implies a potential influence of sex hormones, such as androgens, on disease mechanisms. Despite this, the specific effects of androgens on microglia remain unclear. This study is designed to delineate the interplay between androgens and the survival and inflammatory profile of microglial cells, as well as to explore their contribution to the progression of AD. METHODS AND KEY FINDINGS: To create a chronic androgen deficiency model, 3-month-old wild-type (WT) mice and APP/PS1 mice underwent bilateral orchiectomy (ORX), with age-matched sham-operated controls. Cognitive and memory were evaluated at 5 and 12 months, paralleled by assessments of amyloid-beta (Aß) and microglial morphology in hippocampal and cortical areas. The ORX treatment in mice resulted in diminished microglial populations and morphological alterations, alongside an increase in Aß plaques and a concomitant decline in cognitive performance that exacerbated over time. In vitro, dihydrotestosterone (DHT) was found to stimulate microglial proliferation and ameliorate Aß1-42-induced apoptosis. SIGNIFICANCE: These findings suggested that androgens may exert a protective role, maintaining the normal proliferation and functionality of microglial cells. This preservation could potentially slow the progression of AD. As a result, our study provided a conceptual framework for the development of novel therapeutic strategies for AD.

Mental health disparities in people living with human immunodeficiency virus: A cross-sectional study on physician-patient concordance and treatment regimens.

BACKGROUND: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown. METHODS: A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen's kappa test was used to assess the agreement between physicians and PLWH. RESULTS: The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% (P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis (P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). CONCLUSION: Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

All-2D-Materials Subthreshold-Free Field-Effect Transistor with Near-Ideal Switching Slope.

The Boltzmann Tyranny, set by thermionic statistics, dictates the lower limit of switching slope (SS) of a MOSFET to be 60 mV/dec, the fundamental barrier for low-dissipative electronics. The large SS leads to nonscalable voltage, significant leakage, and power consumption, particularly at short channels, making transistor scaling an intimidating challenge. In recent decades, an array of steep-slope transistors has been proposed; none is close to an ideal switch with ultimately abrupt switching (SS ∼ 0 mV/dec) between the binary logic states. We demonstrated an all-2D-materials van-der-Waals-heterostructure (vdW)-based FET that exhibits ultrasteep switching (0.33 mV/dec), a large on/off current ratio (∼107), and an ultralow off current (∼0.1 pA). The "Subthreshold-Free" operation achieved by the collective behavior of functional materials enables FET switching directly from the OFF-state to the ON-state with entirely eliminated subthreshold region, behaving as the ideal logic switch. Two-inch wafer-scale device fabrication is demonstrated. Boosted by device innovation and emerging materials, the research presents an advancement in achieving the "beyond-Boltzmann" transistors, overcoming one of the CMOS electronics' most infamous technology barriers that have plagued the research community for decades.

Reconfigurable Neuromorphic Computing with 2D Material Heterostructures for Versatile Neural Information Processing.

Reconfigurable neuromorphic computing holds promise for advancing energy-efficient neural network implementation and functional versatility. Previous work has focused on emulating specific neural functions rather than an integrated approach. We propose an all two-dimensional (2D) material-based heterostructure capable of performing multiple neuromorphic operations by reconfiguring output terminals in response to stimuli. Specifically, our device can synergistically emulate the key neural elements of the synapse, neuron, and dendrite, which play important and interrelated roles in information processing. Dendrites, the branches that receive and transmit presynaptic action potentials, possess the ability to nonlinearly integrate and filter incoming signals. The proposed heterostructure allows reconfiguration between different operation modes, demonstrating its potential for diverse computing tasks. As a proof of concept, we show that the device can perform basic Boolean logic functions. This highlights its applicability to complex neural-network-based information processing problems. Our integrated neuromorphic approach may advance the development of versatile, low-power neuromorphic hardware.

Aberration of social behavior and gut microbiota induced by cross-fostering implicating the gut-brain axis.

The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.

Effective surface passivation of GaAs nanowire photodetectors by a thin ZnO capping.

The III-V nanowire (NW) structure is a good candidate for developing photodetectors. However, high-density surface states caused by the large surface-to-volume ratio severely limit their performance, which is difficult to solve in conventional ways. Here, a robust surface passivation method, using a thin layer of ZnO capping, is developed for promoting NW photodetector performance. 11 cycles of ZnO, grown on pure zinc blende high-quality GaAs NWs by atomic layer deposition, significantly alleviates the undesirable effect of the surface states, without noticeable degradation in NW morphology. An average 20-fold increase in micro-photoluminescence intensity is observed for passivated NWs, which leads to the development of detectors with high responsivity, specific detectivity, and optical gain of 9.46 × 105 A W-1, 3.93 × 1014 Jones, and 2.2 × 108 %, respectively, under low-intensity 532 nm illumination. Passivated NW detectors outperform their counterparts treated by conventional methods, so far as we know, which shows the potential and effectiveness of thin ZnO surface passivation on NW devices.

Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy.

Blocking CSF-1/CSF-1R pathway has emerged as a promising strategy to remodel tumor immune microenvironment (TME) by reprogramming tumor-associated macrophages (TAMs). In this work, a novel CSF-1R inhibitor C19 with a highly improved pharmacokinetic profile and in vivo anticolorectal cancer (CRC) efficiency was successfully discovered. C19 could effectively reprogram M2-like TAMs to M1 phenotype and reshape the TME by inducing the recruitment of CD8+ T cells into tumors and reducing the infiltration of immunosuppressive Tregs/MDSCs. Deeper mechanistic studies revealed that C19 facilitated the infiltration of CD8+ T cells by enhancing the secretion of chemokine CXCL9, thus significantly potentiating the anti-CRC efficiency of PD-1 blockade. More importantly, C19 combined with PD-1 mAb could induce durable antitumor immune memory, effectively overcoming the recurrence of CRC. Taken together, our findings suggest that C19 is a promising therapeutic option for sensitizing CRC to anti-PD-1 therapy.

TFEB overexpression through GFAP promoter disrupts neuronal lamination by dysregulating neurogenesis during embryonic development.

INTRODUCTION: Transcription factor EB (TFEB), a key regulator of autophagy and lysosomal biogenesis, has diverse roles in various physiological processes. Enhancing lysosomal function by TFEB activation has recently been implicated in restoring neural stem cells (NSCs) function. Overexpression of TFEB can inhibit the cell cycle of newborn cortical NSCs. It has also been found that TFEB regulates the pluripotency transcriptional network in mouse embryonic stem cells independent of autophagy lysosomal biogenesis. This study aims to explore the effects of TFEB activation on neurogenesis in vivo through transgenic mice. METHODS: We developed a GFAP-driven TFEB overexpression mouse model (TFEB GoE) by crossing the floxed TFEB overexpression mice and hGFAP-cre mice. We performed immunohistochemical and fluorescence staining on brain tissue from newborn mice to assess neurogenesis changes, employing markers such as GFAP, Nestin, Ki67, DCX, Tbr1 and Neun to trace different stages of neural development and cell proliferation. RESULTS: TFEB GoE mice exhibited premature mortality, dying at 10-20 days after birth. Immunohistochemical analysis revealed significant abnormalities, including disrupted hippocampal structure and cortical layering. Compared to control mice, TFEB GoE mice showed a marked increase in radial glial cells (RGCs) in the hippocampus and cortex, with Ki67 staining indicating these cells were predominantly in a quiescent state. This suggests that TFEB overexpression suppresses RGCs proliferation. Additionally, abnormal distributions of migrating neurons and mature neurons were observed, highlighted by DCX, Tbr1 and Neun staining, indicating a disruption in normal neurogenesis. CONCLUSION: This study, using transgenic animals in vivo, revealed that GFAP-driven TFEB overexpression leads to abnormal neural layering in the hippocampus and cortex by dysregulating neurogenesis. Our study is the first to discover the detrimental impact of TFEB overexpression on neurogenesis during embryonic development, which has important reference significance in future TFEB overexpression interventions in NSCs for treatment.

CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer.

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC patients with microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from PD-1 blockade therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components in tumor microenvironment (TME), largely limit the therapeutic efficacy of anti-PD-1 against CRC. The CSF1/CSF1R pathway plays a key role in regulating macrophage polarization, and blocking CSF1R signaling transduction may be a potential strategy to effectively reprogram macrophages and remodel TME. Here, we found that increasing expression of CSF1R in macrophages predicted poor prognosis in CRC cohort. Furthermore, we discovered a novel potent CSF1R inhibitor, PXB17, which significantly reprogramed M2 macrophages to M1 phenotype. Mechanically, PXB17 significantly blocked activation of PI3K/AKT/mTORC1 signaling, resulting in inhibition of cholesterol biosynthesis. Results from 3D co-culture system suggested that PXB17-repolarized macrophages could induce infiltration of CD8+ T lymphocytes in tumors and improve the immunosuppressive microenvironment. In vivo, PXB17 significantly halted CRC growth, with a stronger effect than PLX3397. In particular, PXB17 potently enhanced therapeutic activity of PD-1 mAb in CT-26 (MSS) model and prevented tumor recurrence in MC-38 (MSI-H) model by promoting formation of long-term memory immunity. Our study opens a new avenue for CSF1R in tumor innate and adaptive anti-tumor immunomodulatory activity and suggests that PXB17 is a promising immunotherapy molecule for enhancing the efficacy of PD-1 mAb or reducing tumor recurrence of CRC.

Supercritical water oxidation for the treatment and utilization of organic wastes: Factor effects, reaction enhancement, and novel process.

Supercritical water oxidation (SCWO) has been regarded as a new and efficient technology for the harmless treatment and energy utilization of organic wastes, resulting in the quickly homogeneous oxidation between organics and oxidizers and the former being wholly degraded into small environment-friendly green molecules such as H2O and N2 and inorganic salts. This paper systematically analyzed the influencing behavior and mechanisms of the reaction factors, such as temperature, pressure, residence time, oxidant type, oxidation coefficient, and the concentration and pH values of the raw material, on the treatment effect of organic wastes. For most organic wastes, the SCWO conditions at 550 °C with a residence time of 1min and an oxidation coefficient of 100% can meet the removal rate of more than 99%. To further enhance the degradation rate of organics, the principles, implementation cases, and related equipment components of general enhancement technologies of supercritical water oxidation were discussed, such as fractional oxygen injection, auxiliary fuel co-oxidation, and hydrothermal flame-assisted degradation. This paper proposes a novel supercritical flame-assisted oxidation process in which the reactor performs preheating, corrosion protection, and desalination functions. The use of additive-enhanced oxidation, segmented oxidation, and supercritical hydrothermal flame-assisted oxidation has achieved good results in the complicated treatment process of brutal degradation of organic matter.

High salt diet exacerbates cognitive deficits and neurovascular abnormalities in APP/PS1 mice and induces AD-like changes in wild-type mice.

High salt diet (HSD) is a risk factor of hypertension and cardiovascular disease. Although clinical data do not clearly indicate the relationship between HSD and the prevalence of Alzheimer's disease (AD), animal experiments have shown that HSD can cause hyperphosphorylation of tau protein and cognition impairment. However, whether HSD can accelerate the progression of AD by damaging the function of neurovascular unit (NVU) in the brain is unclear. Here, we fed APP/PS1 mice (an AD model) or wild-type mice with HSD and found that the chronic HSD feeding increased the activity of enzymes related to tau phosphorylation, which led to tau hyperphosphorylation in the brain. HSD also aggravated the deposition of Aß42 in hippocampus and cortex in the APP/PS1 mice but not in the wild-type mice. Simultaneously, HSD caused the microglia proliferation, low expression of Aqp-4, and high expression of CD31 in the wild-type mice, which were accompanied with the loss of pericytes (PCs) and increase in blood brain barrier (BBB) permeability. As a result, wild-type mice fed with HSD performed poorly in Morris Water Maze and object recognition test. In the APP/PS1 mice, HSD feeding for 8 months worsen the cognition and accompanied the loss of PCs, the activation of glia, the increase in BBB permeability, and the acceleration of calcification in the brain. Our data suggested that HSD feeding induced the AD-like pathology in wild-type mice and aggravated the development of AD-like pathology in APP/PS1 mice, which implicated the tau hyperphosphorylation and NVU dysfunction.

In-Plane Ferrielectric Order in van der Waals ß'-In2Se3.

van der Waals ferroic materials exhibit rich potential for implementing future generation functional devices. Among these, layered ß'-In2Se3 has fascinated researchers with its complex superlattice and domain structures. As opposed to ferroelectric α-In2Se3, the understanding of ß'-In2Se3 ferroic properties remains unclear because ferroelectric, antiferroelectric, and ferroelastic characteristics have been separately reported in this material. To develop useful applications, it is necessary to understand the microscopic structural properties and their correlation with macroscopic device characteristics. Herein, using scanning transmission electron microscopy (STEM), we observed that the arrangement of dipoles deviates from the ideal double antiparallel antiferroelectric character due to competition between antiferroelectric and ferroelectric structural ordering. By virtue of second-harmonic generation, four-dimensional STEM, and in-plane piezoresponse force microscopy, the long-range inversion-breaking symmetry, uncompensated local polarization, and net polarization domains are unambiguously verified, revealing ß'-In2Se3 as an in-plane ferrielectric layered material. Additionally, our device study reveals analogous resistive switching behaviors of different types owing to polarization switching, defect migration, and defect-induced charge trapping/detrapping processes.

The role of JAK/STAT signaling pathway in cerebral ischemia-reperfusion injury and the therapeutic effect of traditional Chinese medicine: A narrative review.

Cerebral ischemia is a cerebrovascular disease with symptoms caused by insufficient blood or oxygen supply to the brain. When blood supplied is restored after cerebral ischemia, secondary brain injury may occur, which is called cerebral ischemia-reperfusion injury (CIRI). In this process, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays an important role. It mediates neuroinflammation and participates in the regulation of physiological activities, such as cell proliferation, differentiation, and apoptosis. After CIRI, M1 microglia is activated and recruited by the damaged tissue. The inflammatory factors are produced by M1 microglia through the JAK/STAT pathway, eventually leading to cell apoptosis. Meanwhile, the JAK2/STAT3 signaling pathway and the expression of lipocalin-2 and caspase-3 could increase. In the pathway, phosphorylated JAK2 and phosphorylated STAT3 function of 2 ways. They not only promote the proliferation of neurons, but also affect the differentiation direction of neural stem cells by further acting on the Notch signaling pathway. Recently, traditional Chinese medicine (TCM) is a key player in CIRI, through JAK2, STAT3, STAT1 and their phosphorylation. Therefore, the review focuses on the JAK/STAT signaling pathway and its relationship with CIRI as well as the influence of the TCM on this pathway. It is aimed at providing the basis for future clinical research on the molecular mechanism of TCM in the treatment of CIRI.

Effect of acupuncture on BDNF signaling pathways in several nervous system diseases.

In recent years, the understanding of the mechanisms of acupuncture in the treatment of neurological disorders has deepened, and considerable progress has been made in basic and clinical research on acupuncture, but the relationship between acupuncture treatment mechanisms and brain-derived neurotrophic factor (BDNF) has not yet been elucidated. A wealth of evidence has shown that acupuncture exhibits a dual regulatory function of activating or inhibiting different BDNF pathways. This review focuses on recent research advances on the effect of acupuncture on BDNF and downstream signaling pathways in several neurological disorders. Firstly, the signaling pathways of BDNF and its function in regulating plasticity are outlined. Furthermore, this review discusses explicitly the regulation of BDNF by acupuncture in several nervous system diseases, including neuropathic pain, Parkinson's disease, cerebral ischemia, depression, spinal cord injury, and other diseases. The underlying mechanisms of BDNF regulation by acupuncture are also discussed. This review aims to improve the theoretical system of the mechanism of acupuncture action through further elucidation of the mechanism of acupuncture modulation of BDNF in the treatment of neurological diseases and to provide evidence to support the wide application of acupuncture in clinical practice.

2D Ferroionics: Conductive Switching Mechanisms and Transition Boundaries in Van der Waals Layered Material CuInP2 S6.

The recently unfolded ferroionic phenomena in 2D van der Waals (vdW) copper-indium-thiophosphate (CuInP2 S6 or CIPS) have received widespread interest as they allow for dynamic control of conductive switching properties, which are appealing in the paradigm-shift computing. The intricate couplings between ferroelectric polarization and ionic conduction in 2D vdW CIPS facilitate the manipulation and dynamic control of conductive behaviors. However, the complex interplays and underlying mechanisms are not yet fully explored and understood. Here, by investigating polarization switching and ionic conduction in the temperature and applied electric field domains, it is discovered that the conducting mechanisms of CIPS can be divided into four distinctive states (or modes) with transitional boundaries, depending on the dynamics of Cu ions in the material. Further, it demonstrates that dynamically-tunable synaptic responsive behavior can be well implemented by governing the working-state transition. This research provides an in-depth, quantitative understanding of the complex phenomena of conductive switching in 2D vdW CIPS with coexisting ferroelectric order and ionic disorder. The developed insights in this work lay the ground for implementing high-performance, function-enriched devices for information processing, data storage, and neuromorphic computing based on the 2D ferroionic material systems.

Quality and microbial diversity of homemade bread packaged in cinnamaldehyde loaded poly(lactic acid)/konjac glucomannan/wheat gluten bilayer film during storage.

The current study aimed to reveal the changes in quality and microbial diversity of bread at 25 °C, and to analyze the activity of antifungal bilayer film on maintaining the quality of bread during 10 days of storage. Antifungal bilayer film prepared with cinnamaldehyde loaded polylactic acid/konjac glucomannan/wheat gluten (PLA/KGM/WG-CIN) was used to preserve bread samples fermented at different times. The changes in the morphology, moisture state, texture properties and microbiological analysis of bread were investigated during the storage. Analysis of microbial diversity of bread samples showed a clear decrease in the abundance of the main spoilage fungi (Aspergillus and Penicillium) in samples packed with PLA/KGM/WG-CIN film. The PLA/KGM/WG-CIN film effectively prevented moisture from evaporation, maintained the texture properties, retarded the growth of fungi, and reduced the fungi diversity during the storage. Results suggest a large potential of PLA/KGM/WG-CIN film to ensure the quality and safety of bread products.

Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR.

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1's OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1's and CA2's CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3's CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1's neuronal branches and the CA2's and DG's synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

Single-Transistor Neuron with Excitatory-Inhibitory Spatiotemporal Dynamics Applied for Neuronal Oscillations.

Brain-inspired neuromorphic computing systems with the potential to drive the next wave of artificial intelligence demand a spectrum of critical components beyond simple characteristics. An emerging research trend is to achieve advanced functions with ultracompact neuromorphic devices. In this work, a single-transistor neuron is demonstrated that implements excitatory-inhibitory (E-I) spatiotemporal integration and a series of essential neuron behaviors. Neuronal oscillations, the fundamental mode of neuronal communication, that construct high-dimensional population code to achieve efficient computing in the brain, can also be demonstrated by the neuron transistors. The highly scalable E-I neuron can be the basic building block for implementing core neuronal circuit motifs and large-scale architectural plans to replicate energy-efficient neural computations, forming the foundation of future integrated neuromorphic systems.

Effects of maternal deprivation and environmental enrichment on anxiety-like and depression-like behaviors correlate with oxytocin system and CRH level in the medial-lateral habenula.

The medial-lateral habenula (LHbM)'s role in anxiety and depression behaviors in female mice remains unclear. Here, we used neonatal maternal deprivation (MD) and post-weaning environmental enrichment (EE) to treat female BALB/c offspring and checked anxiety-like and depression-like behaviors as well as the corticotropin-releasing hormone (CRH), oxytocin receptor (OTR), estrogen receptor-beta (ERß) levels in their LHbM at adulthood. We found that MD enhanced state anxiety-like behaviors in the elevated plus-maze test, and EE caused trait anxiety-like behaviors in the open field test and depression-like behaviors in the tail suspension test. The immunochemistry showed that MD reduced OT immunoreactive neuron numbers in the hypothalamic paraventricular nucleus but increased OTR levels in the LHbM; EE increased CRH levels in the LHbM but decreased OTR levels in the LHbM. The additive effects of EE and MD maintained the behavioral parameters, OT-ir neuronal numbers, CRH levels, and OTR levels similar to the additive of non-MD and non-EE. The correlation analysis showed that CRH levels correlated with synaptic connection levels, OTR levels correlated with nucleus densities, and ERß levels correlated with Nissl body levels and body weights in female mice. Neither MD nor EE affected ERß levels in the LHbM. Together, the study revealed the relationships between behaviors and neuroendocrine and neuronal alterations in female LHbM and the effects of experiences including MD and EE on them.