Pathological Behavior Research Articles

The inhibitory control of traveling waves in cortical networks.

Propagating waves of activity can be evoked and can occur spontaneously in vivo and in vitro in cerebral cortex. These waves are thought to be instrumental in the propagation of information across cortical regions and as a means to modulate the sensitivity of neurons to subsequent stimuli. In normal tissue, the waves are sparse and tightly controlled by inhibition and other negative feedback processes. However, alterations of this balance between excitation and inhibition can lead to pathological behavior such as seizure-type dynamics (with low inhibition) or failure to propagate (with high inhibition). We develop a spiking one-dimensional network of neurons to explore the reliability and control of evoked waves and compare this to a cortical slice preparation where the excitability can be pharmacologically manipulated. We show that the waves enhance sensitivity of the cortical network to stimuli in specific spatial and temporal ways. To gain further insight into the mechanisms of propagation and transitions to pathological behavior, we derive a mean-field model for the synaptic activity. We analyze the mean-field model and a piece-wise constant approximation of it and study the stability of the propagating waves as spatial and temporal properties of the inhibition are altered. We show that that the transition to seizure-like activity is gradual but that the loss of propagation is abrupt and can occur via either the loss of existence of the wave or through a loss of stability leading to complex patterns of propagation.

Fiber deprivation and microbiome-borne curli shift gut bacterial populations and accelerate disease in a mouse model of Parkinson’s disease

Parkinson's disease (PD) is a neurological disorder characterized by motor dysfunction, dopaminergic neuron loss, and alpha-synuclein (αSyn) inclusions. Many PD risk factors are known, but those affecting disease progression are not. Lifestyle and microbial dysbiosis are candidates in this context. Diet-driven gut dysbiosis and reduced barrier function may increase exposure of enteric neurons to toxins. Here, we study whether fiber deprivation and exposure to bacterial curli, a protein cross-seeding with αSyn, individually or together, exacerbate disease in the enteric and central nervous systems of a transgenic PD mouse model. We analyze the gut microbiome, motor behavior, and gastrointestinal and brain pathologies. We find that diet and bacterial curli alter the microbiome and exacerbate motor performance, as well as intestinal and brain pathologies, but to different extents. Our results shed important insights on how diet and microbiome-borne insults modulate PD progression via the gut-brain axis and have implications for lifestyle management of PD.

Trichotillomania: a perspective synthesised from neuroscience and lived experience

Trichotillomania, or hair-pulling disorder, is one of a family of disorders called body-focused repetitive behaviours (BFRBs), which also include disordered skin-picking (dermotillomania) and nail-biting (onychophagia). The disorders affect 1%–2% of...

Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.

Depressive-like Behaviors Induced by mGluR5 Reduction in 6xTg in Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one representative dementia characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain, resulting in cognitive decline and memory loss. AD is associated with neuropsychiatric symptoms, including major depressive disorder (MDD). Recent studies showed a reduction in mGluR5 expression in the brains of stress-induced mice models and individuals with MDD compared to controls. In our study, we identified depressive-like behavior and memory impairment in a mouse model of AD, specifically in the 6xTg model with tau and Aβ pathologies. In addition, we investigated the expression of mGluR5 in the brains of 6xTg mice using micro-positron emission tomography (micro-PET) imaging, histological analysis, and Western blot analysis, and we observed a decrease in mGluR5 levels in the brains of 6xTg mice compared to wild-type (WT) mice. Additionally, we identified alterations in the ERK/AKT/GSK-3β signaling pathway in the brains of 6xTg mice. Notably, we identified a significant negative correlation between depressive-like behavior and the protein level of mGluR5 in 6xTg mice. Additionally, we also found a significant positive correlation between depressive-like behavior and AD pathologies, including phosphorylated tau and Aβ. These findings suggested that abnormal mGluR5 expression and AD-related pathologies were involved in depressive-like behavior in the 6xTg mouse model. Further research is warranted to elucidate the underlying mechanisms and explore potential therapeutic targets in the intersection of AD and depressive-like symptoms.

Reversal of pathological motor behavior in a model of Parkinson's disease by striatal dopamine uncaging.

Motor deficits observed in Parkinson's disease (PD) are caused by the loss of dopaminergic neurons and the subsequent dopamine depletion in different brain areas. The most common therapy to treat motor symptoms for patients with this disorder is the systemic intake of L-DOPA that increases dopamine levels in all the brain, making it difficult to discern the main locus of dopaminergic action in the alleviation of motor control. Caged compounds are molecules with the ability to release neuromodulators locally in temporary controlled conditions using light. In the present study, we measured the turning behavior of unilateral dopamine-depleted mice before and after dopamine uncaging. The optical delivery of dopamine in the striatum of lesioned mice produced contralateral turning behavior that resembled, to a lesser extent, the contralateral turning behavior evoked by a systemic injection of apomorphine. Contralateral turning behavior induced by dopamine uncaging was temporarily tied to the transient elevation of dopamine concentration and was reversed when dopamine decreased to pathological levels. Remarkably, contralateral turning behavior was tuned by changing the power and frequency of light stimulation, opening the possibility to modulate dopamine fluctuations using different light stimulation protocols. Moreover, striatal dopamine uncaging recapitulated the motor effects of a low concentration of systemic L-DOPA, but with better temporal control of dopamine levels. Finally, dopamine uncaging reduced the pathological synchronization of striatal neuronal ensembles that characterize unilateral dopamine-depleted mice. We conclude that optical delivery of dopamine in the striatum resembles the motor effects induced by systemic injection of dopaminergic agonists in unilateral dopamine-depleted mice. Future experiments using this approach could help to elucidate the role of dopamine in different brain nuclei in normal and pathological conditions.

Tricin promoted ATG-7 dependent autophagic degradation of α-synuclein and dopamine release for improving cognitive and motor deficits in Parkinson's disease

Tricin, a natural nontoxic flavonoid distributed in grasses and euphorbia plants, has been reported to scavenge free radicals, possess anti-inflammatory and antioxidative effects. However, its autophagic effect on Parkinson's disease (PD) has not been elucidated. By adopting cellular and C. elegans models of PD, the autophagic effect of tricin was identified based on the level of autophagy markers (LC3-II and p62). Besides, the pharmacological effects on neurotransmitters (dopamine), inflammatory cytokines (IFN γ, TNFα, MCP-1, IL-10, IL-6 and IL-17A), histology (hematoxylin & eosin and Nissl staining) and behavioural pathology (open-field test, hindlimb clasping, Y-maze, Morris water-maze and nest building test) were also confirmed in the A53T-α-synuclein transgenic PD mouse model. Further experiments demonstrated that tricin induced autophagic flux and lowered the level of α-synuclein through AMPK-p70s6K- and ATG7-dependent mechanism. Compared to the existing clinical PD drugs, tricin mitigated pathogenesis and symptoms of PD with no observable side effects. In summary, tricin is proposed as a potential adjuvant remedy or nutraceutical for the prevention and treatment of PD.

A coupled model for the dynamics of gas exchanges in the human lung with Haldane and Bohr’s effects

We propose an integrated dynamical model for oxygen and carbon dioxide transfer from the lung into the blood, coupled with a lumped mechanical model for the ventilation process, for healthy patients as well as in pathological cases. In particular, we take into account the nonlinear interaction between oxygen and carbon dioxide in the blood volume, referred to as the Bohr and Haldane effects. We also propose a definition of the physiological dead space volume (the lung volume that does not contribute to gas exchange) which depends on the pathological state and the breathing scenario. This coupled ventilation-gas diffusion model is driven by the sole action of the respiratory muscles. We analyse its sensitivity with respect to characteristic parameters: the resistance of the bronchial tree, the elastance of the lung tissue and the oxygen and carbon dioxide diffusion coefficients of the alveolo-capillary membrane. Idealized pathological situations are also numerically investigated. We obtain realistic qualitative tendencies, which represent a first step towards classification of the pathological behaviours with respect to the considered input parameters.

Integrating multi-omics features for blood-based multi-cancer early detection.

156 Background: The current standard-of-care cancer screening paradigm is constrained to just a few cancer types and has challenges in patient compliance due to the invasive procedures endured from the tests. Recently studies have demonstrated that blood-based multi-cancer detection (MCED) approaches may hold promise for identifying asymptomatic cancer patients from the general population. However, most studies only exploit a single aspect of cancer hallmarks which is challenging for the biological reasons since cancer is a heterogenous disease with a wide spectrum of pathological and clinical behaviors. Methods: Here we report SeekInCare, a CE-IVD Mark MCED test, based on a novel multi-dimensional cancer risk score (CRS) model incorporating copy number aberrations, fragment size, end motifs and oncogenic viruses via shallow whole genome sequencing (sWGS) from cell-free DNA (cfDNA), and seven common tumor markers in a single 8ml blood draw. Results: Our research cohort consisted of 898 healthy subjects and 615 stage I-IV cancer patients that covered eight common cancers and 19 uncommon cancer types. The CRS model identified 427 cancer patients with 69.4% sensitivity at 98.0% specificity, resulting in an AUC (area under the curve) of 0.926. The sensitivities were 50.3%, 64.0%, 73.8% and 86.2% in stage I, II, III and IV cancers respectively. The sensitivities of eight common cancer types, breast, stomach, lung, colorectum, lymphoma, liver, pancreas and leukemia, were 45.1%, 50.0%, 63.4%, 69.4%, 70.5%, 81.4%, 82.4% and 90.9% respectively. We also prospectively evaluated SeekInCare in a real-world cohort consisting of 1212 subjects who received the test as a LDT (laboratory developed test) (median follow-up time: 753 days, range: 78~1669 days). 13 out of 18 cancer cases were detected while 46 subjects tested positive but without cancer. Thus, SeekInCare achieved 72.2% sensitivity, 96.1% specificity, 22.0% PPV and 99.6% NPV in the real-world cohort. Conclusions: In this study, we provided a non-invasive MCED test (SeekInCare) based on the multi-omics and multi-dimensional features. The case-control study demonstrated that SeekInCare could detect >20 cancer types with 69.4% sensitivity at 98.0% specificity. The outstanding real-world performance of SeekInCare warrants future investigation of its clinical utility and health economics as a mass cancer screening test in average-risk populations.

Upregulation of S100A6 and its relation with CD34+ cells apoptosis in high-risk myelodysplastic syndromes patients

ObjectivesMyelodysplastic syndromes (MDS) are a group of myeloid malignancies characterized by peripheral blood cytopenia and hematopoietic dysplasia that often progress to acute myeloid leukemia (AML). Increased apoptosis of normal hematopoietic cells and decreased apoptosis of malignant clonal hematopoietic cells in patients with MDS is some of the mechanisms leading to ineffective hematopoietic cells in the bone marrow. S100 calcium-binding protein A6 (S100A6) is upregulated in many malignancies. The overexpression of S100A6 in these malignancies has been associated with proliferation, migration, and invasion phenotypes in cancer cells, and we aimed to investigate the expression of S100A6 in CD34+ cells and the relationship between S100A6 expression and apoptosis of CD34+ cells in high-risk patients with MDS. MethodsWe measured S100A6 mRNA expression in bone marrow (BM) CD34+ cells from high-risk patients with MDS using RT-PCR. Next, we examined S100A6 expression in CD34+ cells using flow cytometry. We also analyzed the correlation between CD34+ cell apoptosis and S100A6 expression in high-risk patients with MDS. ResultsOur data showed increased S100A6 mRNA expression in CD34+ cells in patients with MDS (1.05 ± 0.69 vs. 0.17 ± 0.12; P＜0.01). The expression of S100A6 in BM CD34+ cells also increased (58.40 ± 13.18 vs. 45.83 ± 15.01). The expression of S100A6 in CD34+ cells and apoptosis of CD34+ cells were negatively correlated in patients (r = −0.75; P < 0.01). ConclusionsCollectively, S100A6 may be a potential marker of CD34+ cells in high-risk patients with MDS and may participate in the pathological behaviors of CD34+ cells, such as evasion of apoptosis. Thus, S100A6 may be a potential target for eliminating minimal residual disease.

Heart Rhythm Analysis Using Nonlinear Oscillators with Duffing-Type Connections

Heartbeat rhythms are related to a complex dynamical system based on electrical activity of the cardiac cells usually measured by the electrocardiogram (ECG). This paper presents a mathematical model to describe the electrical activity of the heart that consists of three nonlinear oscillators coupled by delayed Duffing-type connections. Coupling alterations and external stimuli are responsible for different cardiac rhythms. The proposed model is employed to build synthetic ECGs representing a variety of responses including normal and pathological rhythms: ventricular flutter, torsade de pointes, atrial flutter, atrial fibrillation, ventricular fibrillation, polymorphic ventricular tachycardia and supraventricular extrasystole. Moreover, the sinoatrial rhythm variations are described by time-dependent frequency, representing transient disturbances. This kind of situation can represent transitions between different pathological behaviors or between normal and pathological physiologies. In this regard, a nonlinear dynamics perspective is employed to describe cardiac rhythms, being able to represent either normal or pathological behaviors.

Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders

Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.

Purity or perversion? from taboo to fact: kindergarten teachers' reflections on age-normal sexuality.

Many educators and pedagogues around the world face challenging situations in their everyday work. Being caught off guard when children begin to explore their bodies and show curiosity about body parts and sexual issues is one of the most uncomfortable realities in the work of educating our children and can generate a series of worrying questions, such as, "Is this child* normal? Should I stop him/ her from masturbating? What should I tell him/her?. Although talking to children about body changes and sexual matters may seem strange or embarrassing, providing correct and age-appropriate information is one of the most important things kindergarten employees can do to ensure that children grow up protected, healthy and safe in their bodies. The current study is based on empirical evidence from focus group interviews with 18 kindergarten teachers from four different kindergartens. The aim is to provide a real overview regarding kindergarten employees' experiences when it comes to their work with sexual development in small children. The findings show that sexuality is still a taboo even in western societies, as it is usually linked to abuse or pathological behavior. Additionally, key information about lack of focus on these topics in pedagogical educational programs is provided. Furthermore, the informants highlight the importance of knowledge and resources for them to feel in control and in confidence to face these challenges. Future directions and tips are provided to improve the educational field and ensure a healthy and balanced development which is after all part of all children's rights.

PENTINGNYA PEMILIHAN Peer Group DALAM PENCEGAHAN PENYALAHGUNAAN NAPZA DI KALANGAN PELAJAR SMA 14 MAKASSAR

This Community Service Program aims to provide knowledge about the importance of selecting Peer Groups in preventing drug abuse among students of SMA 14 Makassar. Drug abuse is so dangerous because it can form pathological behavior and is usually carried out by individuals who have a vulnerable personality or have a high risk, and if done for a certain period of time will cause bio-psycho-social-spiritual disturbances. This community service implementation method consists of two stages, namely: 1) Distribution of extension materials; 2) Presentation of material and providing education with the lecture method; 3) Provide feedback as an evaluation to determine student understanding of the material presented. The results show that this counseling provides additional knowledge about the importance of the peer group approach. The Peer Group approach in preventing drug abuse is carried out so that the peer group that is formed in adolescents has an understanding of the dangers of drugs and will influence their peer group to avoid drug abuse. The main purpose of forming a peer group is to keep youth away from drug abuse. The vulnerability of adolescents is trapped in a negative peer group, because at that time they experience a crisis of identity, "who am I". Therefore, there is a need for adolescents to form their identity as "who" or "as" what. If they are facilitated or intervened to be involved in positive and interested activities, then this will really help youth to find their identity and also get support or reinforcement from the group. At the end of this activity, small groups of 7-10 people were formed based on their interests and talents, a leader was determined and they were asked to discuss the activities they would carry out in the future. The results of the discussion are then conveyed to the school and other parties who can assist in implementing the group activities so that they become positive activities

Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.

Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations. A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms "venous malformation," "lymphatic malformation," "lymphaticovenous malformation," "genetic variant," "genetic mutation," "endothelial cells," and "animal model." Relevant publications were reviewed and summarized. The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments. Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.

The brain serotonin system in autism.

Autism spectrum disorders (ASDs) are among themost common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, byrepetitive behavior, and often anxiety and learning disabilities. The brain serotonin (5-HT) system is known to becrucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for invivo regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter inthe mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT-related drugs have potential for ASD treatment.

Gambling, sports psychiatry, and disciplinary sanctions in English professional football

This paper critically examines the broader implications of the recent case involving the professional football player, Ivan Toney, who was sanctioned by the English Football Association for gambling-related offences. Gambling and English professional football have many interconnections, underscored by the prominent betting culture within the sport and athletes’ distinctive risk factors for pathological behaviours. Common punitive measures for betting-related offences, like complete bans from “all football-related activity”, may inadvertently exacerbate extant vulnerabilities, particularly in cases where gambling disorder has been noted as a mitigating circumstance. Accordingly, this article recommends holistic approaches to such incidents, emphasising the need to balance applicable punishments with the provision of sufficient mental health support informed by current evidence. Moreover, a wider reconsideration of the potentially harmful intersections between gambling and English professional football may be necessary, involving proactive initiatives to expand prevention schemes, increase psychoeducation, and reduce mental health stigma in football.

Adaptive weighting of Bayesian physics informed neural networks for multitask and multiscale forward and inverse problems

In this paper, we present a novel methodology for automatic adaptive weighting of Bayesian Physics-Informed Neural Networks (BPINNs), and we demonstrate that this makes it possible to robustly address multi-objective and multiscale problems. BPINNs are a popular framework for data assimilation, combining the constraints of Uncertainty Quantification (UQ) and Partial Differential Equation (PDE). The relative weights of the BPINN target distribution terms are directly related to the inherent uncertainty in the respective learning tasks. Yet, they are usually manually set a-priori, that can lead to pathological behavior, stability concerns, and to conflicts between tasks which are obstacles that have deterred the use of BPINNs for inverse problems with multiscale dynamics.The present weighting strategy automatically tunes the weights by considering the multitask nature of target posterior distribution. We show that this remedies the failure modes of BPINNs and provides efficient exploration of the optimal Pareto front. This leads to better convergence and stability of BPINN training while reducing sampling bias. The determined weights moreover carry information about task uncertainties, reflecting noise levels in the data and adequacy of the PDE model.We demonstrate this in numerical experiments in Sobolev training, and compare them to analytically ε-optimal baseline, and in a multiscale Lotka-Volterra inverse problem. We eventually apply this framework to an inpainting task and an inverse problem, involving latent field recovery for incompressible flow in complex geometries.

A Lipid Droplet-Specific NIR Fluorescent Probe with a Large Stokes Shift for In Vivo Visualization of Polarity in Contrast-Induced Acute Kidney Injury.

The research on lipid droplets (LDs) has attracted great attention in the field of biomedical science in recent years. LD malfunction is found to be associated with the development of acute kidney injury (AKI). To monitor this biological process and explain related pathological behavior, the development of excellent LD fluorescent probes with a polarity-sensitive character would provide a desirable strategy. Herein, we designed a new polarity-susceptible fluorescent probe named LD-B with LD targetability, which exhibits very weak fluorescence in highly polar solvents based on the twisted intramolecular charge transfer effect but enhanced fluorescence in low polar environments, enabling us to visualize polarity alteration. The probe LD-B also possesses the merits of intense near-infrared (NIR) emission, good photostability, large Stokes shift, low toxicity, faster metabolic rate, and wash-free ability; thereby, it would contribute to efficient LD fluorescence visualization application. Using LD-B via confocal laser scanning fluorescence imaging and a small-animal imaging system in vivo, we first manifested a prominent rise of LD polarity in contrast-induced AKI (CI-AKI), not only at the cellular level but also in animals in vivo. Furthermore, the in vivo studies suggest that LD-B could accumulate in the kidney. In addition, the normal cell lines (including kidney cells) exhibiting a greater polarity of LDs than the cancer cells have been demonstrated systemically. Altogether, our work presents an effective approach for the medical diagnosis of LDs related to CI-AKI and identification of potential therapeutic markers.

PD-L1 Expression is Linked to Tumor-Infiltrating T-Cell Exhaustion and Adverse Pathological Behavior in Pheochromocytoma/Paraganglioma

Pheochromocytoma/paraganglioma (PPGL) is an endocrine-related tumor associated with excessive catecholamine release and has limited treatment options once metastasis occurs. Although recent phase 2 clinical trials of immune checkpoint inhibitors in the treatment of PPGL have preliminarily shown promising results, the fundamentals of immunotherapy for PPGL have not yet been established. In the early research, using bulk RNA sequencing of tumor samples from 7 PPGL patients, we found that PPGL tumor tissues exhibited high PD-L1 mRNA expression compared with adjacent normal adrenal medulla tissues, and this was related to T-cell exhaustion biomarkers. To further validate the association, in this study (n = 60), we first stratified all PPGL samples according to PD-L1 expression as determined by immunohistochemical staining, and then subjected 23 fresh PPGL tumor samples from the cohort to a quantitative polymerase chain reaction (n = 16), flow cytometry (n = 7), and multiplex-immunofluorescence staining. Subsequently, we evaluated the pathological manifestations of all 60 PPGL tumor samples and analyzed the correlation among PD-L1 expression, adverse pathological behavior, various clinicopathological data, and genotypes in PPGL. The results showed that PD-L1-positive expression correlated with the exhaustion of tumor-infiltrating T cells, preoperative abnormal elevation of plasma norepinephrine, high Ki67 index, and adverse pathological behavior in PPGL but not with genetic mutation or metastatic disease, possibly due to the limitation of the small number of patients with metastatic disease (n = 4) in the study cohort. In conclusion, our findings reveal that PD-L1 expression is associated with T-cell exhaustion and adverse pathological behavior in PPGL. These results are expected to provide a new theoretical basis and clinical guidance for the treatment of PPGL.