The brain was previously believed to be an “immune privileged” organ without an immune system. However, recent discoveries have shown a connection between the peripheral lymphatic system and the brain. This review article provides an overview of the three distinct lymphatic systems within the brain - the glymphatic, meningeal, and parenchymal systems - with a focus on the recently discovered deep brain parenchymal lymphatic vessels. The article also discusses how these lymphatic systems are regulated by various pathological conditions, including Alzheimer’s disease, Parkinson’s disease, and other neurological disorders. By shedding light on the link between these diseases and the brain lymphatic systems, the article emphasizes the importance of understanding these systems for potential therapeutic interventions to treat neurodegenerative and psychiatric disorders.
Endogenous retroviruses (ERVs), remnants of ancient viral invasions, make up a significant part of the mammalian genomes. ERVs are typically held in check by complex epigenetic mechanisms, which serve to limit their expansion and potential adverse effects on the genome. However, ERVs can become aberrantly activated in response to stressful challenges, contributing to progression in pathological conditions, including cancer, inflammation, auto-immune disorders, and aging, through various mechanisms. Notably, ERV activation is also detected in the brain and is increasingly recognized as an important factor in neuropsychiatric disorders. In this review, we encapsulate the general understanding of ERVs in both physiological and pathological states and compiled evidence for ERV activation across a spectrum of neuropsychiatric disorders, along with current studies exploring the underlying mechanisms. Despite the accumulating body of evidence, research in this field remains in its infancy and faces substantial challenges. Further studies are warranted to enhance our understanding of ERV activation mechanisms and their roles in neuropsychological conditions, potentially contributing to the development of innovative therapeutic interventions.
Sleep disruption is common in older adults and has been linked to many negative health outcomes, including impaired cognitive, emotional, and interpersonal functioning and maladaptive metabolic changes. Sleep disturbance is the most common symptom in depressive patients, and it was formerly thought to be a major secondary manifestation of depression. Many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression in older adults, with bidirectional relationships between sleep quality and depression. This narrative review summarizes recent research or evidence on the sleep–depression association in older adults, as well as the potential common mechanisms underlying the comorbidity of sleep and depression disorders, focusing on the clock system, neurochemical substrates, and neurocircuits. A better understanding of the pathophysiological mechanisms underlying sleep disturbance and depression can assist psychiatrists in better managing this comorbidity.
Purpose We aimed to explore the relationship between thyroid peroxidase antibody (TPO-Ab) and suicidal and aggressive behaviors in patients with major mental disorders. Methods We enrolled 812 inpatients with major mental disorders (schizophrenia, bipolar disorder, and major depressive disorder) in this retrospective study. Baseline interviews were conducted by two psychiatrists. The patients’ suicidal and aggressive behaviors were recorded in the electronic medical record system and these patients were evaluated in terms of violence and suicide behaviors according to the risk assessment form formulated in the Work Code for the Management and Treatment of Severe Mental Illness by the Ministry of Health of China. We calculated the incidence rates of positive TPO-Ab, the suicidal and aggressive behaviors. Furthermore, we explored the relationships among risk factors for suicidal and aggressive behaviors using logistics regression analysis. Results Among the 812 patients, 42.6% (n = 346) had TPO-Abs and were defined as the positive group. Rates of suicide and aggression among the enrolled patients were 12.7% (n = 103) and 10.2% (n = 83) respectively. The percentage of patients with aggressive behaviors (13%, n = 45) was higher than that in the negative group (8.2%, n = 38). In contrast, the incidence (9.5%) of suicidal behaviors in the positive group was lower than that (15.0%) in the negative group. TPO-Ab was found to increase the risk of aggressive behavior (odd ratio (OR) = 1.64, 95%CI (1.04, 2.59), P = 0.03) and this effect was still evident after we adjusted for thyroid function (OR = 1.65, 95%CI (1.03, 2.64), P = 0.04). Furthermore, subclinical hypothyroidism (OR = 2.64, 95%CI (1.19, 5.85), P = 0.02) and subclinical hyperthyroidism (OR = 7.03, 95%CI (2.23, 22.20), P = 0.001) were found to be risk factors of aggressive behavior but not for suicide behaviors. Conclusion TPO-Abs can affect aggressive behavior but do not affect suicidal behaviors, in patients with major mental disorders. Thus, antibody testing is necessary for psychiatric patients with aggressive behavior. The TPO-Ab test helped the psychiatric staff to determine aggressive behavior in advance.
The ten-eleven translocation 2 (Tet2) protein, a member of the Tet family, acts as an α-ketoglutarate- and Fe2+-dependent dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine. Tet2 is widely recognized for its involvement in diverse physiological and pathological processes. Herein, we focused on Tet2 changes in stress-related disease models, behavioral changes in response to mutant forms of Tet2, and potential mechanisms underlying the involvement of Tet2 in psychiatric symptoms. This information can contribute to the comprehensive understanding of the role of Tet2 in stress-related disorders and its potential as a therapeutic target.
Motor neuron diseases (MND) are a group of rare neurodegenerative diseases that significantly affect the survival of patients. The disease progresses rapidly, and currently, there is no cure for MND. Therefore, delays in MND progression and improvements in the patient’s quality of life have become crucial aspects of clinical work. Stress—a response to environmental or psychological changes—significantly affects body metabolism. In particular, excessive stress can harm the human body. Here, we review recent literature exploring the impact of stress on the progression of MND. This review also discusses the potential mechanisms of stress-induced MND deterioration, including activation of the hypothalamic–pituitary–adrenal axis, abnormal microglial activation, oxidative stress, and the accumulation of stress granules. The role of stress in the pathological changes of MND and the importance of stress management in the treatment of MND have been emphasized. Here, we highlight that the attention of clinicians to this crucial aspect can significantly influence the course and outcome of the disease.
Physical exercise generally improves health in humans and animals and may enhance cognitive function and neural function in the brain, especially in the prefrontal cortex and hippocampus. It is also a promising intervention for brain disorders such as psychiatric conditions and neurodegenerative diseases. The neuroprotective mechanisms of exercise are related to synaptic plasticity, neurogenesis, and autophagy. Moreover, the therapeutic effects of exercise are associated with glial cell function in the brain. In this review, we examine the relationship between glial cell function and brain disorders. We also consider the role of glial cells in modulating the effects of exercise on the molecular mechanisms and neural circuits involved in central and peripheral brain function. This review demonstrates that glial cells may play an important role in the effects of physical exercise interventions on the brain, particularly in those with neurological disorders.
Background:Depressive disorder is a common disease characterized by depressed mood and loss of pleasure, which often brings a great grief to patients and a huge burden to the society. Currently, the therapeutic strategy has made a rapid progress, but even the most well-studied and commonly used antidepressants will take weeks to produce a desired effect and have some side-effects. Besides, the objective and specific diagnostic indexes are still absent. Many important hypotheses have been proposed and inflammation is one of them. Among the inflammatory cytokines that might be closely related to depression, HMGB1 is a novel and vital one.Methods:We reviewed and analyzed literature on PubMed and web of science using the relevant key words ( "depression/MDD" in conjunction with "HMGB1/high mobility group box 1).Results:We found that both clinical and laboratory studies demonstrated pro-inflammatory role of HMGB1 in depressive disorder, while conditional knockout or inhibition of HMGB1 could alleviate inflammation and depression.Conclusion:Therefore, in this review we will talk about the possible role of HMGB1 in the development of depressive disorder and the underlying mechanisms with the hope of providing evidence for a novel and effective therapy for depressive disorder.
The corona virus disease 2019 (COVID-19) is an epidemic pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to pulmonary symptoms and a variety of physical symptoms, patients also experience symptoms of cognitive impairment. Previous studies have shown that many patients will experience varying degrees of cognitive decline in the subacute and prognostic stages after having COVID-19. Then, what are the factors that lead to cognitive decline? This article reviews and analyzes the inherent factors before the onset of the disease, the factors directly related to the disease, and the factors of hospital admission. In addition, this paper also summarizes the evaluation methods of cognitive decline and the possible mechanisms of the pathogenesis, thus providing corresponding clinical intervention ideas for inhibiting or regulating related factors.
Background:Awe promotes altruistic behavior by enhancing the sense of the small self. However, this mediation mechanism has not been consistently replicated, possibly due to variations in the types of awe. No studies have directly examined whether the mediation of the sense of the small self between awe and altruistic behavior holds true in general, or is specific to a certain type of awe induction. Here, we describe an experiment aimed to address this issue.Methods:Two hundred and thirty-five participants were randomly assigned to different emotion groups, including natural awe, social awe, spiritual awe, amusement, and neutrality. After emotional manipulation, the participants were informed of a student’s misfortune and asked to decide how much of their experimental compensation money (RMB 50) they would donate.Results:We observed a promoting effect of awe induction on monetary donation in general, and this effect was similar across the three types of awe. Further mediation analysis indicated that natural awe, uniquely promoted altruistic behavior via the mediation role of the small self.Conclusion:The current study demonstrates the novel insight that, although the different types of awe induction similarly promote altruistic behavior, only natural awe promotes altruistic behavior through increasing sense of the small self.
Background:The neuropeptide galanin has been shown to exhibit anticonvulsant effects in animal models. However, only a few studies have attempted to identify the galanin receptor subtype (s) involved in this effect. In the present study, the expression of galanin and that of its receptors in a rat model of temporal lobe epilepsy was studied to reveal the epileptogenesis-related alterations.Methods:Pilocarpine-inducted status epilepticus (SE) rat model was used for temporal lobe epilepsy. Galanin and galanin receptor mRNA was detected by Real-time polymerase chain reaction in dorsal hippocampus of rats at three different time points following SE: at the acute phase (24h), latent period (7 days), and chronic epileptic period (8 weeks). Using immunohistochemistry, galanin positive fibers and bodies were also observed.Results:In the acute seizure phase, a significant up-regulation of the galanin mRNA was observed in the hippocampus. Meanwhile, galanin-positive cells appeared, while galanin-positive fibers disappeared in the hilus of the dentate gyrus, stratum radiatum of CA1, and stratum lucidum of CA3, indicating an increase in galanin synthesis and release during the acute seizure phase. The gene expression analysis also indicated a significant increase in the transcription of galanin receptors GalR1 and GalR3 24h after SE. The increased levels of GalR1 mRNA were also observed in the latent and chronic epileptic periods.Conclusion:In general, these data suggest that adaptive changes occur in the galanin system during epileptogenesis that may affect its antiepileptic effects. Furthermore, these changes should be taken into account when attempting to pharmacologically modulate this system.
Background:With the COVID-19 pandemic in the first half of 2020, most colleges in China delayed in-person instruction. During this period, interpersonal isolation (social isolation) emerged, which created a natural "laboratory" for examining students’ attitudes and feelings toward social interaction. This study aimed to analyze the mediating effect of sense of security (SS) and the moderating effect of social perception on the associations between interpersonal competence (IC) and the presence of meaning.Methods:A cross-sectional study was conducted among 1161 university students after the COVID-19 lockdown in China. A structural equation modeling approach was applied to examine the mediating effect of SS on the association between the presence of meaning and IC. A multigroup analysis was used to comprehend the moderating effect of social perception on the model.Results:SS indicated a complete mediating effect on the path from IC to the presence of meaning in the social preference group. Meanwhile, the moderating effect of social perception mainly occurred on the pathway of IC to SS between the social avoidance and social preference groups.Conclusions:IC influences the presence of meaning through different paths for different groups. University students with social preference are more capable of obtaining SS from their IC and further experience more meaning in life.
Background:To explore changes in the first clinic visits in adolescents diagnosed with mood disorders, anxiety disorders, or childhood mood disorders from January 2019 to May 2022 based on outpatient records from a large psychiatric hospital in China.Methods:The medical records of adolescents aged 12–17 years at their first clinic visits from January 2019 to May 2022 were collected at Ningbo Kangning Hospital. Adolescents primarily diagnosed with mood disorders, anxiety disorders, or childhood affective disorders were included in the present study.Results:The results showed that the number of adolescents at their first clinic visits diagnosed with mood disorders, anxiety disorders, and childhood affective disorders according to the International Classification of Diseases-10 (ICD-10) increased each year, with an increase from 2019 to 2020 being greater than that from 2020 to 2021. The mean age at first diagnosis showed a significant trend towards younger age (P < 0.001). The mean age when boys did their first clinic visits in 2021 was significantly younger than that in 2019 (P < 0.05) and the mean age of girls in 2021 was significantly younger than that in 2019 (P < 0.001) and in 2020 (P < 0.001). No difference was found in terms of sex (Chi-square = 7.538, P > 0.05).Conclusion:The number of first clinic visits by adolescent patients with mood, anxiety, or childhood affective disorders increased during the COVID-19 pandemic. The use of universal, selective, and indicated prevention and treatment strategies to buffer children and adolescents from negative mental health outcomes is imperative in the context of the COVID-19 pandemic.
Background:Despite accumulating evidence suggesting the tight relationship between human conscious experiences and cardiopulmonary metabolism, the psychophysiological basis underlying this relationship remains unclear. In this study, we present the hypothesis that the oxygen-delivering efficacy of the cardiopulmonary metabolism contributes to the conscious experiences.Method:To test this hypothesis, we carried out a large cohort of investigations with regards to mental imagery, to highlight the connection of visual imagery vividness with oxygen‐delivering ability in an organism. The properties of the red blood cells, under the control of immune cells, played significant roles in this phenomenon. Additionally, we combined the hyperbaric oxygen treatment approach and the conscious awareness detection tasks to demonstrate that the improved cardiopulmonary metabolism accelerated and promoted the processing and strength of conscious awareness along with the intensified attention executive control ability.Results:The results provided experimental evidence for the association of cardiopulmonary metabolism with consciousness, in conjunction with the executive role of mental imagery.Discussion:Overall, the data highlights the essential role of the oxygen available in the body, in the integrity of cardiopulmonary metabolism, which is related to consciousness, and further implies that the internal consciousness experience may exhibit executive control in psychology and physiology homeostasis.
Animals use cognitive behavior, by integrating information from multiple senses, to cope with the complex and changing environment. However, it is not yet understood how single sensory cognitive processes get modified and combined by multisensory cognition in these environments. To address this question, we exposed mouse to positive (tactile experience enrichment (TEE)) and negative (chronic restraint stress (CRS)) environments, and then studied how the dependence of their behavior on unimodal sensory (tactile or visual) processing was influenced by different environments. We found that TEE promoted object recognition behavior that depended on vision or tactile participation alone, whereas CRS impaired this dependence of behavior on single sensory channels. These results suggest that a positive environment promotes unimodal cognitive behavior, while the behavioral effect of negative environments is the opposite.
Sensory neurons, also known as afferent neurons, perceive noxious stimuli from internal as well as external environments through nociceptive receptors and then transmit these signals to the central nervous system. Similarly, the innate immune system also recognizes external and internal danger signals from invading microbes or tissue injuries. The immune system and sensory neurons share mechanisms to respond to pathogen/damage-associated molecular patterns (PAMPs/DAMPs) through pattern recognition receptors. Recent studies have identified an inseparable bidirectional connection between sensory neurons and the immune system that is important for maintaining tissue homeostasis and regulating inflammatory states, as well as affecting the progression of inflammatory diseases. This review summarizes the recent findings on the crosstalk between sensory neurons and local immunity in peripheral tissues, including the skin, respiratory system, gastrointestinal tract, cornea, and joints. Understanding the mechanisms of this interaction can help in the development of therapeutic strategies to treat peripheral inflammatory diseases.
Obesity has become a worldwide disease, posing a rapidly increasing challenge to the global healthcare system. The primary reason for obesity is that food intake exceeds the body’s needs. The central nervous system monitors the body’s energy status by continuously receiving peripheral gut-derived signals and functions as a master regulator in controlling feeding behaviors. Vagal afferents transmit gut-derived consumption signals from the periphery to the hindbrain (e.g., the nucleus of the solitary tract (NTS)). In contrast, vagal efferent nerves send commands to regulate peripheral organ activities. However, the precise role of the gut–vagus–NTS pathway and the gut–brain axis in regulating food intake is not yet fully understood. This review highlights the key roles of the NTS, vagal sensory neurons, and the gastrointestinal system in regulating feeding behaviors.
Beta-Ca2+/calmodulin-dependent protein kinase II (βCaMKII) is known as a powerful regulator of lateral habenula neuron function and a key molecular determinant of depression. βCaMKII is also abundant in the hippocampus, especially in the dentate gyrus (DG). However, whether βCaMKII in the DG is also involved in emotional behaviors remains unknown. In this study, using βCaMKII-F90G transgenic mice, in which the overexpression of βCaMKII is restricted to the DG, we demonstrated that βCaMKII overexpression in the DG has no effect on the level of anxiety in mice in open field test or light–dark box test. Moreover, tail suspension test and forced swim test showed that the level of depression in βCaMKII-F90G transgenic mice and their littermates was comparable. Taken together, our findings indicate that βCaMKII overexpression in the DG does not result in depression- and anxiety-like behaviors in mice and provide evidence that the function of βCaMKII in emotional behaviors is brain region specific.
