Brain, behavior, & immunity - health最新文献

Importance

Despite the major implications of executive deficits in day-to-day functioning, few studies have investigated this in post-acute sequelae of SARS-CoV-2 infection using standardized measures that differentiate between aspects of executive function.

Objective

Examine whether SARS-CoV-2 infection is associated with deficits in executive functions and if so, investigate the duration of this association.

Design, Setting, and Participants

The present research has a cross-sectional design and uses data from the Norwegian Covid-19 Cohort study. The current cohort (n = 8102) completed the Behavior Rating Inventory of Executive Function- Adult Version (BRIEF-A) electronically between April 2021 and September 2021. During the assessment, 4183 of the included participants had a prior positive polymerase chain reaction test (PCR) for SARS-CoV-2 and 3919 were untested or had a confirmed negative PCR test.

Exposure

Laboratory-confirmed SARS-CoV-2 infection.

Main outcomes and measures

Executive functions were measured using the BRIEF-A, a self-report questionnaire comprising 75 items within nine theoretically and empirically distinct clinical scales. All participants self-reported on demographical variables and comorbidity. Information on sex and age was derived from the personal identification number, and vaccination status was obtained from the Norwegian Immunization Registry (SYSVAK).

Results

Participants with a positive SARS-CoV-2 status reported executive deficits in everyday life above the clinical threshold (T-score ≥65) more often than non-infected controls (383 vs. 225). Specifically, the SARS-CoV-2 positive status group indicated significantly more deficits related to metacognition, with the greatest difference demonstrated for working memory. This difference remained when adjusting for various demographic factors and comorbidities, with significantly greater odds of reporting above the clinical threshold following SARS-CoV-2 infection, as observed on the global executive composite score 6–12 months after infection (OR 1.97; 95% CI 1.51 to 2.55).

Conclusions

Our study confirms more perceived executive deficits following SARS-CoV-2 infection compared to non-infected controls, with metacognitive aspects being the most affected. These findings shed light on the potential functional difficulties that individuals may encounter during the post-acute phase of SARS-CoV-2 infection and may guide further development of targeted interventions addressing metacognitive domains of executive functioning.

Background

We compared heart rate variability (HRV) indices between people living with HIV (PLWH) and HIV-negative individuals to ascertain the independent association between HIV infection and reduced HRV, and further investigated whether distinct clinical laboratory profiles exist between PLWH with and without reduced HRV.

Methods

This cross-sectional analysis included 304 PLWH and 147 HIV-negative individuals with comparable age and sex. Thirty-two routine clinical laboratory indices (including hematology and biochemistry) closest to the survey were extracted from the Electronic Medical Record System. HRV indices were divided into two categories: low (lowest quartile, Q1) and moderate-to-high (combined, Q2‒Q4).

Results

The time domain indices, ln(SDNN), ln(RMSSD), and ln(PNN50), as well as the frequency domain indices, ln(HF), ln(LF), and ln(VLF), were all significantly reduced in PLWH versus HIV-negative individuals (all p < 0.05). These associations remained for ln(SDNN), ln(PNN50), ln(HF) and ln(LF) even after adjusting for potential confounders in multivariable models. PLWH with low HRV indices exhibited distinct clinical laboratory profiles that were characterized by an elevation in fasting plasma glucose, white blood cell count, neutrophil count, neutrophil%, and a reduction in albumin, total protein, urine creatinine, lymphocyte%, red blood cell count (RBC) and nadir CD4 count. The final stepwise logistic regression models for low SDNN included older age, decreased total cholesterol levels, elevated neutrophil count, and the use of antidiabetic medications, whereas the final model for low LF included older age, reduced RBC and the use of antidiabetic medications.

Conclusion

PLWH exhibit impaired parasympathetic activity, as evidenced by reduced SDNN, PNN50, LF and HF. Furthermore, PLWH who have reduced HRV indices exhibits distinct clinical laboratory profiles that are related to systematic inflammatory response and diabetes.

How can we learn more about pain without causing pain in humans or animals? This short review focuses on neuro-glial primary cell cultures as models to study neuro-immune interactions in the context of pain and discusses their advantages and limitations.

The field of basic pain research places scientists in an ethical dilemma. We aim to understand underlying mechanisms of pain for an improved pain therapy for humans and animals. At the same time, this regularly includes the induction of pain in model animals. Within the field of psychoneuroimmunology, the examination of the complexity of neuro-immune interactions in health and disease as well as the bi-directional communication between the brain and the periphery make animal experiments an inevitable part of pain research. To address ethical and legal considerations as well as the growing societal awareness for animal welfare, scientists push for the identification and characterization of complementary methods to implement the 3R principle of Russel and Burch. As such, methods to replace animal studies, reduce the number of animals used, and refine experiments are tested. Neuro-glial primary cell cultures of structures of the nociceptive system, such as dorsal root ganglia (DRG) or the spinal dorsal horn (SDH) represent useful in vitro tools, when research comes to a cellular and molecular level. They allow for studying mechanisms of neuronal sensitization, glial cell activation, or the role of specific inflammatory mediators and intracellular signaling cascades involved in the development of inflammatory and neuropathic pain. Moreover, DRG/SDH-cultures provide the opportunity to test novel strategies for interventions, such as pharmaceuticals or cell-based therapies targeting neuroinflammatory processes. Thereby, in vitro models contribute to a better understanding of neuron-glia-immune communication in the context of pain and in the advancement of pain therapies. However, this can only be one piece in a large puzzle. Our knowledge about the complexity of pain will depend on studies in humans and animals applied in vitro and in vivo and will benefit from clear and open-minded interdisciplinary communication and transparency in public outreach.

Depression is a psychological disorder associated with prolonged stress, which involves abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated levels of glucocorticoids (GC). Excessive GC can cause damage to the structure and function of the hippocampus, thereby triggering depressive symptoms. Studies suggest that the bile acid receptor farnesoid X receptor (FXR) may play a role in adrenal GC synthesis. This study aimed to explore the potential therapeutic effects of dried bear bile (DBB) on depression and its mechanism. We used the chronic unpredictable mild stress (CUMS) mouse model and FXR agonist GW4064 stimulated mice, as well as H295R human adrenal cortical carcinoma cells, employing behavioral tests, biochemical analysis, and gene expression analysis to assess the effects of DBB treatment on depressive behavior, serum corticosterone (CORT) levels, and adrenal FXR and steroid biosynthesis-related gene expression. The results showed that in both CUMS and GW4064-stimulated mice, DBB treatment significantly improved depressive-like behaviors and reversed serum CORT levels. Additionally, DBB suppressed the expression of steroidogenic regulatory genes in the adrenal glands of CUMS mice. In H295R cells, DBB treatment effectively reduced cortisol secretion induced by Forskolin, inhibited the expression of steroid biosynthesis-related genes, and suppressed cortisol production and HSD3B2 expression under conditions of FXR overexpression and FXR activation. Our findings suggest that DBB regulates adrenal FXR to modulate glucocorticoid synthesis and exerts antidepressant effects. DBB may serve as a potential therapeutic agent for depression by regulating GC levels and steroidogenesis pathway. Further research is underway to test the antidepressant effects of each DBB component to understand their specific contribution.

Many patients with depressive disorder do not respond to conventional antidepressant treatment. There is an ongoing interest in investigating potential mechanisms of treatment resistance in depression to provide alternative treatment options involving inflammatory mechanisms. Increasing evidence implicates the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome as a critical factor in neuroinflammation. ATP-induced P2X7 receptor (P2X7R) activation is a major trigger for inflammation, activating the canonical NLRP3 inflammatory cascade. Psychosocial stress, the primary environmental risk factor for depression, is associated with changes in ATP-mediated P2X7R signaling. Depression and stress response can be alleviated by Cannabidiol (CBD). CBD has an anti-inflammatory activity related to the regulation of NLRP3 inflammasome activation. However, CBD's effects on the inflammasome pathway are poorly understood in central nervous system (CNS) cells, including microglia, astrocytes, and neurons. This review will emphasize some findings for neuroinflammation and NLRP3 inflammasome pathway involvement in depression, particularly addressing the ATP-induced P2X7R activation. Moreover, we will underline evidence for the effect of CBD on depression and address its potential impacts on neuroinflammation through the NLRP3 inflammasome cascade.

The gut microbiota begins to colonize the host body following birth, develops during the suckling period and changes to the adult type after weaning. The early gut microbiota during the suckling period is thought to have profound effects on the host physiology throughout life but it is still unclear whether early dysbiosis is retained lifelong. Our previous study indicated that chronic nasal inflammation induces dysbiosis of gut microbiota in adult mice. In the present study, we addressed the question as to whether early exposure to chronic nasal inflammation induces dysbiosis, and if so, whether the dysbiosis is retained until adulthood and the sex differences in this effect. Male and female mice received repeated intranasal administration of lipopolysaccharide (LPS) or saline twice a week from P7 to P24 and were weaned at P24. The cecal contents were obtained for 16S rRNA analysis at 2 time points: at 4 weeks (wks), just after weaning, and at maturation to adulthood at 10 wks. The body weight did not differ between saline- and LPS-treated mice till around weaning, suggesting that the mothers’ milk was given similarly to all mice. At 4 wks, the beta diversity was significantly different between saline- and LPS-treated male and female mice and the composition of the gut microbiota changed in LPS-treated mice. The abundance of phylum Bacteroidota tended to decrease and that of Firmicutes increased in LPS-treated male mice, while the abundance of Deferribacterota increased in LPS-treated female mice. At 10 wks, the beta diversity was not different between saline- and LPS-treated mice, but the abundance of family Lachnospiraceae significantly decreased in LPS-treated male and female mice by LEfSe analysis. Together, chronic nasal inflammation early in life caused transient and long-term dysbiosis of gut microbiota, which may contribute to the onset and progress of metabolic and neuropsychiatric disorders.

Caregiving adversity (CA) exposure is robustly linked to increased risk for poor oral, physical, and mental health outcomes. Increasingly, the gut microbiome has garnered interest as a contributor to risk for and resilience to such health outcomes in CA-exposed individuals. Though often overlooked, the oral microbiome of CA-exposed individuals may be just as important a contributor to health outcomes as the gut microbiome. Indeed, outside the context of CA, the oral microbiome is well-documented as a regulator of both oral and systemic health, and preliminary data suggest its association with mental health. However, research examining the association between CA and the oral microbiome is extremely sparse, especially in childhood, when the community composition of such organisms is still stabilizing. To address that sparsity, in the current study, we examined composition and differential abundance metrics of the oral microbiome in 152 youth aged 6–16 years, who had either been exposed to significant caregiving adversity (significant separation from or maltreatment by a caregiver; N = 66, CA) or who had always remained with their biological/birth families (N = 86, Comparison). We identified a significant negative association between hair cortisol and oral microbiome richness in the Comparison group that was significantly blunted in the CA group. Additionally, youth in the CA group had altered oral microbiome composition and elevated abundance of potentially pathogenic bacteria relative to youth in the Comparison group. Questionnaire measures of fatigue, somatic complaints, and internalizing symptoms had limited associations with oral microbiome features that were altered in CA. Although we found differences in the oral microbiomes of CA-exposed youth, further research is required to elucidate the implications of those differences for health and well-being.

Post-menopausal persons living with HIV (PWH) report elevated levels of psychological stress and monocyte activation compared to persons living without HIV (PWOH). Resting state functional connectivity (rsFC) of mesolimbic brain regions underpinning stress and emotion regulation are susceptible to inflammatory insult. Although psychological stress is elevated, rsFC reduced, and CD16⁺ monocytes overexpressed in the brains of PWH, it is unclear whether the relationships amongst these variables differ compared to PWOH.

An ethnically diverse sample of postmenopausal women, 24 PWH and 30 PWOH provided self-report mood surveys and provided peripheral blood specimens to quantify LPS-stimulated CD16^+/− expression of TNF-α via flow cytometric analysis. An anatomical and resting state functional MRI scan were used to derive time-series metrics of connectivity between the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) as well as the amygdala.

A positive association was observed between levels of perceived stress and CD16^+/− TNF-α in both LPS-stimulated and unstimulated cells. PLWH showed lower connectivity between mPFC and NAcc. In turn, lower rsFC between these regions predicted greater psychological stress and proportion of CD16⁻, but not CD16⁺, cells expression of TNF-α.

Neuroimmune effects of monocyte inflammation on the functional connectivity of mesolimbic regions critical for discrimination of uncertainty-safety and reward signals were observed in an ethnically diverse sample of postmenopausal women living with and without HIV. PWH showed lower mPFC-NAcc functional connectivity, which in turn was associated with greater perceived stress.