Rasoul Mirzaei, B. Bouzari, S. R. Hosseini-Fard
et al.
During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.
In response to various types of environmental and cellular stress, microglia rapidly activate and exhibit either pro- or anti-inflammatory phenotypes to maintain tissue homeostasis. Activation of microglia can result in changes in morphology, phagocytosis capacity, and secretion of cytokines. Furthermore, microglial activation also induces changes to cellular energy demand, which is dependent on the metabolism of various metabolic substrates including glucose, fatty acids, and amino acids. Accumulating evidence demonstrates metabolic reprogramming acts as a key driver of microglial immune response. For instance, microglia in pro-inflammatory states preferentially use glycolysis for energy production, whereas, cells in anti-inflammatory states are mainly powered by oxidative phosphorylation and fatty acid oxidation. In this review, we summarize recent findings regarding microglial metabolic pathways under physiological and pathological circumstances. We will then discuss how metabolic reprogramming can orchestrate microglial response to a variety of central nervous system pathologies. Finally, we highlight how manipulating metabolic pathways can reprogram microglia towards beneficial functions, and illustrate the therapeutic potential for inflammation-related neurological diseases.
Abstract Background The transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) presents significant challenges for young people with eating disorders and their families. These transitions often occur during critical periods of neurological, social-emotional development, and major life changes, all of which can influence broader psychosocial and treatment outcomes. This study represents the initial phase of a broader co-production project aimed at developing a new intervention model, Transition for Eating Disorder Youth intervention (TEDYi), and explored the lived experiences of young people, carers, and mental health professionals during transitions. Methods Fifteen semi-structured interviews were conducted with young people (n = 6) and carers (n = 9), alongside two focus groups involving 12 mental health professionals. These took place across six NHS sites in England, including two adult and four adolescent specialist eating disorder services. Results The data were analysed with Reflexive Thematic Analysis (RTA) which revealed four key themes: navigating the complexity of transitions, we need carers involved, the shadow of separation, and suggestions for the TEDYi intervention related to coping strategies and self-management. Conclusions These findings have significant clinical implications for transitional care, emphasising the need for a more standardised and supportive approach to the transition from CAMHS to AMHS. The forthcoming intervention model seeks to address these challenges, with this study helping to prioritise key areas identified by TEDYi, which has been endorsed as a preparatory resource for enhancing clinical practice.
B cells represent a relatively minor cell population within both the healthy and diseased central nervous system (CNS), yet they can have profound effects. This is emphasized in multiple sclerosis, in which B cell-depleting therapies are arguably the most efficacious treatment for the condition. In this Review, we discuss how B cells enter and persist in the CNS and how, in many neurological conditions, B cells concentrate within CNS barriers but are rarely found in the parenchyma. We highlight how B cells can contribute to CNS pathology through antibody secretion, antigen presentation and secretion of neurotoxic molecules, using examples from CNS tumours, CNS infections and autoimmune conditions such as neuromyelitis optica and, in particular, multiple sclerosis. Overall, understanding common and divergent principles of B cell accumulation and their effects within the CNS could offer new insights into treating these devastating neurological conditions. Although B cells represent only a minor cell population in the central nervous system (CNS), they can contribute to CNS pathology — most notably in multiple sclerosis — through antibody and effector molecule secretion and antigen presentation. Here, Jain and Yong discuss the roles of B cells in the CNS and examine the potential for targeting these cells in various neurological conditions.
Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide.
Fibroblast growth factors (FGFs) act as key signalling molecules in brain development, maintenance, and repair. They influence the intricate relationship between myelinating cells and axons as well as the association of astrocytic and microglial processes with neuronal perikarya and synapses. Advances in molecular genetics and imaging techniques have allowed novel insights into FGF signalling in recent years. Conditional mouse mutants have revealed the functional significance of neuronal and glial FGF receptors, not only in tissue protection, axon regeneration, and glial proliferation but also in instant behavioural changes. This review provides a summary of recent findings regarding the role of FGFs and their receptors in the nervous system and in the pathogenesis of major neurological and psychiatric disorders.
Sarah R. Ocañas, Kevin D. Pham, Jillian E. J. Cox
et al.
Abstract Background Microglia, the brain’s principal immune cells, have been implicated in the pathogenesis of Alzheimer’s disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD. Here, we examined and compared transcriptomic and translatomic sex effects in young and old murine hippocampal microglia. Methods Hippocampal tissue from C57BL6/N and microglial NuTRAP mice of both sexes were collected at young (5–6 month-old [mo]) and old (22–25 mo) ages. Cell sorting and affinity purification techniques were used to isolate the microglial transcriptome and translatome for RNA-sequencing and differential expression analyses. Flow cytometry, qPCR, and imaging approaches were used to confirm the transcriptomic and translatomic findings. Results There were marginal sex differences identified in the young hippocampal microglia, with most differentially expressed genes (DEGs) restricted to the sex chromosomes. Both sex chromosomally and autosomally encoded sex differences emerged with aging. These sex DEGs identified at old age were primarily female-biased and enriched in senescent and disease-associated microglial signatures. Normalized gene expression values can be accessed through a searchable web interface ( https://neuroepigenomics.omrf.org/ ). Pathway analyses identified upstream regulators induced to a greater extent in females than in males, including inflammatory mediators IFNG, TNF, and IL1B, as well as AD-risk genes TREM2 and APP. Conclusions These data suggest that female microglia adopt disease-associated and senescent phenotypes in the aging mouse hippocampus, even in the absence of disease pathology, to a greater extent than males. This sexually divergent microglial phenotype may explain the difference in susceptibility and disease progression in the case of AD pathology. Future studies will need to explore sex differences in microglial heterogeneity in response to AD pathology and determine how sex-specific regulators (i.e., sex chromosomal or hormonal) elicit these sex effects.
Amelie S. Lotz-Havla, Sabrina Katzdobler, Brigitte Nuscher
et al.
To pave the way for healthy aging in early treated phenylketonuria (ETPKU) patients, a better understanding of the neurological course in this population is needed, requiring easy accessible biomarkers to monitor neurological disease progression in large cohorts. The objective of this pilot study was to investigate the potential of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as blood biomarkers to indicate changes of the central nervous system in ETPKU. In this single-center cross-sectional study, GFAP and NfL concentrations in serum were quantified using the Simoa® multiplex technology in 56 ETPKU patients aged 6–36 years and 16 age matched healthy controls. Correlation analysis and hierarchical linear regression analysis were performed to investigate an association with disease-related biochemical parameters and retinal layers assessed by optical coherence tomography. ETPKU patients did not show significantly higher GFAP concentrations (mean 73 pg/ml) compared to healthy controls (mean 60 pg/ml, p = 0.140). However, individual pediatric and adult ETPKU patients had GFAP concentrations above the healthy control range. In addition, there was a significant association of GFAP concentrations with current plasma tyrosine concentrations (r = −0.482, p = 0.036), a biochemical marker in phenylketonuria, and the retinal inner nuclear layer volume (r = 0.451, p = 0.04). There was no evidence of NfL alterations in our ETPKU cohort. These pilot results encourage multicenter longitudinal studies to further investigate serum GFAP as a complementary tool to better understand and monitor neurological disease progression in ETPKU. Follow-up investigations on aging ETPKU patients are required to elucidate the potential of serum NfL as biomarker.
Self-Confidence is a person's belief in all aspects of the advantages he has and that belief makes him feel able to achieve various goals in his life. This study aims to examine the effectiveness of CBT group counseling with symbolic modeling techniques and role play techniques on increasing students' self-confidence. This study used a pretest and multiple posttest designs. Purposive sampling technique was used to select 21 experimental subjects who were placed into three groups randomly so that each group consisted of seven students. The results of the mixed repeated measure ANOVA test showed that the CBT group counseling with symbolic modeling and role play techniques was effective in increasing students' self-confidence. This study found that the combination of symbolic modeling techniques and role play techniques shows interesting implications, so the implications of using this combination of techniques in group counseling practice are recommended in the implementation of CBT counseling.
Introduction
Migratory flows are increasing more and more, especially regarding the refugee crisis during the last years. There are around 86,7 million migrants in Europe. Migrants share similar experiences that may affect their physical and mental health, such as loss of a social network, lack of economical support or high levels of stress and discrimination.
Objectives
To analyze the obstacles that migrants must face to obtain a mental health assistance and the importance of an intercultural approach.
Methods
A narrative review of the existing literature on the subject.
Results
Although there exists evidence that shows that migrants tend to have more health needs, they usually seek less medical advice and receive a poor-quality attention, fulfilling the inverse-care law. This is due to several reasons. Many migrants are excluded of the health care system due to bureaucratic impediments. Also, the language has a determining role, since a higher quality of communication could lead to a better understanding of the symptoms, reducing the risk of erroneous evaluations. Besides, different background and culture between the patient and the doctor can result in lack of communication, mistrust, mistreatment, poor adherence, and worse prognosis.
Conclusions
Despite the exponential growth of migration in the last decade and the continue progression, migrants still face many barriers to receive healthcare. It is necessary to do more research on the mental health of migrants and ethnic minorities to ensure quality care to different cultures.
Disclosure
No significant relationships.
Gul Arga, Hatice Gul Erkol, Esra Cakmak Taskin
et al.
The clinical manifestations of SARS-CoV-2 infection mainly involve the respiratory system. However, there is increasing evidence that this virus can affect other organs, causing a wide range of clinical symptoms. This is the report of a 40-day-old patient who presented with sepsis and had no risk factors other than SARS-CoV-2 infection, whose radiological findings were compatible with cerebral sinus vein thrombosis.
Isabel Cristina Bandeira, Isabel Cristina Bandeira, Lucas Giombelli
et al.
The relationship between epilepsy and psychiatric comorbidities has been recognized for centuries, but its pathophysiological mechanisms are still misunderstood. It is biologically plausible that genetic or epigenetic variations in genes that codify important neurotransmitters involved in epilepsy as well as in psychiatric disorders may influence the development of the latter in patients with epilepsy. However, this possibility remains poorly investigated. The aim of this study was to evaluate the methylation profile of the BDNF and SLC6A4, two genes importantly involved in neuroplasticity, in patients with temporal lobe epilepsy (TLE) regarding the development or not of psychiatric comorbidities. One hundred and thirty-nine patients with TLE, 90 females and 45 males, were included in the study. The mean age of patients was 44.0 (+12.0) years, and mean duration of epilepsy was 25.7 (+13.3) years. The Structured Clinical Interview for DSM-IV shows that 83 patients (59.7%) had neuropsychiatric disorders and 56 (40.3%) showed no psychiatric comorbidity. Mood disorders were the most common psychiatric disorder observed, being present in 64 (46.0%) of all 139 patients. Thirty-three (23.7%) patients showed anxiety disorders, 10 (7.2%) patients showed history of psychosis and 8 (5.8%) patients showed history of alcohol//drug abuse. Considering all 139 patients, 18 (12.9%) demonstrated methylation of the promoter region of both BDNF and SLC6A4 genes. A significant decreased methylation profile was observed only in TLE patients with mood disorders when compared with TLE patients without a history of mood disorders (O.R. = 3.45; 95% C.I. = 1.08–11.11; p = 0.04). A sub-analysis showed that TLE patients with major depressive disorder mostly account for this result (O.R. = 7.20; 95% C.I. = 1.01–56.16; p = 0.042). A logistic regression analysis showed that the independent factors associated with a history of depression in our TLE patients was female sex (O.R. = 2.30; 95% C.I. = 1.02–5.18; p = 0.044), not controlled seizures (O.R. = 2.51; 95% C.I. = 1.16–5.41; p = 0.019) and decreased methylation in BDNF and SLC6A4 genes (O.R. = 5.32; 95% C.I. = 1.14–25.00; p = 0.033). Our results suggest that BDNF or SLC6A4 genes profile methylation is independently associated with depressive disorders in patients with epilepsy. Further studies are necessary to clarify these matters.
Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology. Diseases of the nervous system
Introduction
Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique allowing to induce changes in oscillatory activity. Theta activity has been reported to play a major role in maintenance of information in working memory (WM).
Objectives
The current study had the initial goal to check the effect of theta tACS on accuracy and resting state EEG in a set of match-to-sample WM tasks.
Methods
In the first experiment, we tested 31 participants in the WM task after 20-min tACS applied at Fpz and CPz at 6 Hz, 1 mA.). In the second experiment, we compared the after-effects and online effects of the stimulation in a sample of 25 individuals. Five similar 25-min blocks filled with the same working memory task were distributed over 3 days. We assessed the same group of participants in all three sessions. On the Training day, the participants performed one block without stimulation. On the Sham-Verum day (SV), the first block with Sham stimulation followed by the second block with Verum stimulation. On the Verum-Sham day (VS), the blocks order reversed.
Results
After-effects of the stimulation did not produce any significant changes either in behavior (accuracy in the task) or resting-state EEG (theta frequency band spectral power in the first experiment. In the second experiment, 6 Hz tACS delivered before the WM task was not able to produce any observable changes in working memory performance. The same hold true for online stimulation.
Conclusions
Theta frequency tACS applied to Fpz-CPz electrodes is not an efficient method to improve WM.