Neuroimmunomodulation最新文献

Introduction: Major depressive disorder (MDD) is one of the most prevalent mental disorders associated with various negative impacts such as lower overall quality of life, increased morbidity risk, and even premature mortality. According to the biopsychosocial model of health and disease, multiple factors contribute to the development and manifestation of MDD. Here, we assessed preselected social, psychological, and biological variables and tested their power to predict MDD diagnosis using logistic regression models.

Methods: In 24 patients with current MDD diagnosis and 35 healthy control participants, the following variables were measured to test for associations with MDD diagnosis: (1) emotional neglect and adult attachment style as social variables, (2) thought suppression and cognitive reappraisal as psychological variables, and (3) mitochondrial density (citrate synthase activity as a surrogate marker of mitochondrial density) measured in peripheral blood mononuclear cells (PBMCs) as a biological variable.

Results: The following biopsychosocial variables were associated with MDD diagnosis. Participants with greater emotional neglect (OR: 1.273, 95% CI: 1.059-1.645), higher levels of intrusive thoughts (OR: 1.738, 95% CI: 1.282-3.066), and decreased mitochondrial density in PBMCs (OR: 0.298, 95% CI: 0.083-0.784) had a higher probability of belonging to the MDD group.

Conclusions: In line with biopsychosocial models of depression, the present results indicate that variables at different levels of analysis are conjointly related to MDD. These findings open new perspectives for the diagnosis and treatment of MDD, but they need to be replicated in larger samples in the future.

Background: Neuroinflammation is a central and dynamic driver in the pathophysiology of multiple neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Rather than being a mere consequence of neuronal injury, inflammatory processes, mediated by microglia, astrocytes, peripheral immune cells, and a range of molecular mediators, actively influence disease onset, progression, and clinical manifestations.

Summary: This review aims to synthesize current insights into the cellular and molecular mechanisms that orchestrate neuroinflammatory responses, emphasizing both convergent and disease-specific pathways. It examines the interaction between innate and adaptive immunity in shaping neuronal vulnerability, as well as the bidirectional communication between systemic and central immune systems. Special emphasis is placed on emerging therapeutic strategies, such as immunomodulatory drugs, glial-targeted interventions, and innovative delivery platforms. The discussion integrates findings from diverse disease models and disciplines to identify translational challenges and potential paths toward precision neuroimmunology.

Key messages: The impact of neuroinflammation arises from a complex interaction of shared and disease-specific immune pathways, with both innate and adaptive mechanisms shaping neuronal vulnerability. The crosstalk between peripheral and central immune compartments further modulates disease course, underscoring the importance of understanding these interactions in therapeutic design. While emerging strategies targeting neuroinflammation, including immunomodulatory drugs, glial-focused interventions, and novel delivery platforms, hold considerable promise, their translation into clinical benefit requires overcoming challenges in specificity, safety, and delivery. Ultimately, integrating multidisciplinary insights into immune-brain communication will be critical to advancing precision medicine approaches for neurodegenerative disorders.

Background: Extensive evidence from animal and human studies indicates that exposure to stress during sensitive developmental periods significantly increases the risk for psychiatric and physical disorders, resulting in reduced longevity. Chronic immune activation has been suggested as one pathway through which early adverse experiences may become biologically embedded. This paper highlights selected key findings and questions that first emerged in the literature and founded the field and then examines how research methods and questions have evolved over time.

Summary: During the past decades, evidence from preclinical, clinical, and epidemiological studies has accumulated suggesting consequences of early life stress (ELS) exposure for immune function, particularly increased chronic inflammation or inflammatory responses. Scientific approaches to study the effects of ELS on the immune system have changed since the first studies on this topic were published.

Key messages: Across different study designs, species, and methods, a consistent association between childhood adversity and a pro-inflammatory phenotype has been reported. We critically discuss which topics warrant further consideration and how current findings could be used to develop targeted interventions to prevent or reverse the biological embedding of ELS and resultant disease manifestations.

Introduction: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions.

Methods: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA).

Results: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1β (IL-1β) levels were significantly higher in the LPS1+SD group than in the Saline group.

Conclusion: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone.

Background: It was known since the 1940s that pharmacological administration of glucocorticoids can inhibit inflammatory and immune processes, and these hormones are still today among the most widely used therapeutic tools to treat diseases with immune components. However, it became clear later that endogenous glucocorticoids can either support or restrain immune processes.

Summary: Early studies showed that (a) endogenous levels of glucocorticoids can modulate immune cell activity; (b) the immune response itself can stimulate the hypothalamus-pituitary-adrenal (HPA) axis to release glucocorticoids to levels that can exert immunoregulatory effects; (c) immune products, later identified as cytokines, mediate this effect. On these bases, the existence of a glucocorticoid-mediated immunoregulatory circuit was proposed. It was also shown that increased levels of endogenous glucocorticoids exert protective effects during infections and other diseases with immune components. However, it was found in animal models and in humans that these effects can be blunted in several immune-linked diseases by defects at several levels, for example, by glucocorticoid resistance or by adrenal insufficiency. Evidence was later provided that the glucocorticoid-mediated immunoregulatory circuit can also be activated by cytokines produced not only as consequence of immune stimulation but also following psycho/sensorial and physical stimuli. Thus, this circuit can be integrated at brain levels and, besides stimulating the HPA axis, cytokines can also affect synaptic plasticity, most likely via a tripartite synapse, with astrocytes as neuro-immune cells acting as the third component.

Key messages: It is now well established that the glucocorticoid-mediated immunoregulatory circuit plays a central role in maintaining health. However, several variables can condition the efficacy of the effect of endogenous glucocorticoids. Furthermore, since cytokines and other immune products have many other neuroendocrine and metabolic effects, other neuroendocrine-immune circuits could simultaneously operate or become predominant during different pathologies. The consideration of these aspects might help to implement strategies to eventually decrease therapeutic doses of exogenous glucocorticoids.

Background: Establishing causal relationships is essential in biology and medicine. However, various notions of causality have been operationalized at different times in various fields of the life and health sciences. While this is expected from a history or sociology of science point of view, as different accounts may correspond to what is valued in terms of establishing causal relationships at different times as well as in different fields of biology and medicine, this may come as a surprise for a present-day actor in those fields. If, over time, causal accounts have not been fully dismissed, then they are likely to invite some form of, potentially salutary, explanatory pluralism.

Summary: In the decades following WWII, psychosomatic medicine could propose that psychological factors cause somatic diseases. But today, most medicine has to meet the standard of a randomized clinical trial before any causal relationship can be proposed. Instead, in biology, mechanisms seem to be the most-valued causal discourse to explain how phenomena of interest are brought about. Here, the focus will be on how psychoneuroimmunology, an interdisciplinary research field addressing interactions between the nervous system and immune system, and between behavior and health, has considered causal relationships between psychological factors and cancer.

Key messages: When it comes to causal explanations of links between psychological factors and cancer, psychoneuroimmunology is invited to consider the question of the directionality of these links as well as what and how factors causally contribute to cancer.

Background: Chemokine ligands and their corresponding receptors are essential for regulating inflammatory responses. Chemokine receptors can stimulate immune activation or inhibit/promote signaling pathways by binding to specific chemokine ligands. Among these receptors, CC chemokine receptor 1 (CCR1) is extensively studied as a G protein-linked receptor target, predominantly expressed in various leukocytes, and is considered a promising target for anti-inflammatory therapy. Furthermore, CCR1 is essential for monocyte extravasation and transportation in inflammatory conditions. Its involvement in inflammatory diseases of the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease, and stroke, has been extensively studied along with its ligands. Animal models have demonstrated the beneficial effects resulting from inhibiting CCR1 or its ligands.

Summary: This review demonstrates the significance of CCR1 in CNS inflammatory diseases, the molecules implicated in the inflammatory pathway, and potential drugs or molecules for treating CNS diseases. This evidence may offer new targets or strategies for treating inflammatory CNS diseases.