Biomedicines

Research

31 pages, 3620 KiB

Open AccessArticle

The Association of the Oral Microbiota with the Effects of Acid Stress Induced by an Increase of Brain Lactate in Schizophrenia Patients

by Wirginia Krzyściak, Paulina Karcz, Beata Bystrowska, Marta Szwajca, Amira Bryll, Natalia Śmierciak, Anna Ligęzka, Aleksander Turek, Tamas Kozicz, Anna E. Skalniak, Paweł Jagielski, Tadeusz J. Popiela and Maciej Pilecki

Biomedicines 2023, 11(2), 240; https://doi.org/10.3390/biomedicines11020240 - 17 Jan 2023

Cited by 5 | Viewed by 2150

Abstract

The altered cerebral energy metabolism central to schizophrenia can be linked to lactate accumulation. Lactic acid is produced by gastrointestinal bacteria, among others, and readily crosses the blood–brain barrier, leading to the brain acidity. This study aimed to examine the association of the [...] Read more.

The altered cerebral energy metabolism central to schizophrenia can be linked to lactate accumulation. Lactic acid is produced by gastrointestinal bacteria, among others, and readily crosses the blood–brain barrier, leading to the brain acidity. This study aimed to examine the association of the oral microbiota with the effects of acid stress induced by an increase of brain lactate in schizophrenia patients. The study included patients with a diagnosis of acute polyphasic psychotic disorder meeting criteria for schizophrenia at 3-month follow-up. Results: Individuals with a significantly higher total score on the Positive and Negative Syndrome Scale had statistically significantly lower lactate concentrations compared to those with a lower total score and higher brain lactate. We observed a positive correlation between Actinomyces and lactate levels in the anterior cingulate cap and a negative correlation between bacteria associated with lactate metabolism and some clinical assessment scales. Conclusions: Shifts in the oral microbiota in favour of lactate-utilising bacterial genera may represent a compensatory mechanism in response to increased lactate production in the brain. Assessment of neuronal function mediated by ALA-LAC-dependent NMDA regulatory mechanisms may, thus, support new therapies for schizophrenia, for which acidosis has become a differentiating feature of individuals with schizophrenia endophenotypes. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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14 pages, 2577 KiB

Open AccessArticle

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

by Donglin Yi, Kangmin Kim, Minsu Lee, Eui-man Jung and Eui-Bae Jeung

Biomedicines 2023, 11(1), 35; https://doi.org/10.3390/biomedicines11010035 - 23 Dec 2022

Cited by 2 | Viewed by 1391

Abstract

D5, a member of the cyclic siloxane family, is widely used in personal care products such as shampoo, cosmetics, and deodorant and as an industrial intermediate. D5 can mainly be absorbed orally or through inhalation. Through these routes, people are exposed to D5 [...] Read more.

D5, a member of the cyclic siloxane family, is widely used in personal care products such as shampoo, cosmetics, and deodorant and as an industrial intermediate. D5 can mainly be absorbed orally or through inhalation. Through these routes, people are exposed to D5 daily. However, the risk of prenatal exposure to D5 has not been fully elucidated. In this study, the effect of D5 on neural development was established through behavioral tests on offspring mice. The result confirmed that the maternal administration of 12 mg/kg of D5 showed depression in tail suspension and decreased performance in the forced swimming test as well as an increase in repetitive activity in both the marble-burying test and grooming test compared to the vehicle group. Furthermore, the 12 mg/kg group showed a decrease in cognitive ability and social behavior in the three-chamber test. In the novel object recognition test, memory impairment and a lack of exploring ability were found in the 12 mg/kg group. In conclusion, it is suggested that maternal D5 exposure has developmental neurotoxicity and can cause behavioral disorders in the offspring of mice. Thus, the usage of D5 needs to be considered carefully. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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16 pages, 3255 KiB

Open AccessArticle

The Effect of Disulfiram and Copper on Cellular Viability, ER Stress and ALDH Expression of Human Meningioma Cells

by Ying Kao, Li-Chun Huang, Shao-Yuan Hsu, Shih-Ming Huang and Dueng-Yuan Hueng

Biomedicines 2022, 10(4), 887; https://doi.org/10.3390/biomedicines10040887 - 12 Apr 2022

Cited by 1 | Viewed by 2267

Abstract

(1) Background: Meningiomas are the most common intracranial tumors in adults; currently there is no effective chemotherapy for malignant meningiomas. The effect of disulfiram (DSF)/Copper (Cu) on meningiomas remains unclear; (2) Methods: The impact of DSF/Cu on cell viability of meningioma adhesion cells [...] Read more.

(1) Background: Meningiomas are the most common intracranial tumors in adults; currently there is no effective chemotherapy for malignant meningiomas. The effect of disulfiram (DSF)/Copper (Cu) on meningiomas remains unclear; (2) Methods: The impact of DSF/Cu on cell viability of meningioma adhesion cells (MgACs) and sphere cells (MgSCs) was assessed via MTS assay. The effects of DSF/Cu on intracellular Cu levels, cell senescence, and apoptosis were analyzed using CopperGreen, C₁₂FDG, and Annexin V assays. Intracellular ALDH isoform expression and canonical pathway expression after DSF/Cu treatment were analyzed using mRNA microarray and Ingenuity Pathway Analysis, with further verification through qRT-PCR and immunoblotting; (3) Results: The viability of MgACs and MgSCs were inhibited by DSF/Cu. DSF/Cu increased intracellular Cu levels and cellular senescence. DSF/Cu also induced ER stress in MgACs and activated the PERK/eIF2 pathway for further adaptive response, apoptosis, and autophagy. Finally, DSF/Cu inhibited the expression of different ALDH isoforms in MgACs and MgSCs; (4) Conclusions: DSF/Cu exerts cytotoxic effects against both meningioma cells and stem-like cells and has treatment potential for meningioma. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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Review

Jump to: Research, Other

15 pages, 662 KiB

Open AccessReview

Stem Cell Therapies in Movement Disorders: Lessons from Clinical Trials

by Luca Marsili, Jennifer Sharma, Tiago Fleming Outeiro and Carlo Colosimo

Biomedicines 2023, 11(2), 505; https://doi.org/10.3390/biomedicines11020505 - 9 Feb 2023

Viewed by 2796

Abstract

Stem cell-based therapies (SCT) to treat neurodegenerative disorders have promise but clinical trials have only recently begun, and results are not expected for several years. While most SCTs largely lead to a symptomatic therapeutic effect by replacing lost cell types, there may also [...] Read more.

Stem cell-based therapies (SCT) to treat neurodegenerative disorders have promise but clinical trials have only recently begun, and results are not expected for several years. While most SCTs largely lead to a symptomatic therapeutic effect by replacing lost cell types, there may also be disease-modifying therapeutic effects. In fact, SCT may complement a multi-drug, subtype-specific therapeutic approach, consistent with the idea of precision medicine, which matches molecular therapies to biological subtypes of disease. In this narrative review, we examine published and ongoing trials in SCT in Parkinson’s Disease, atypical parkinsonian disorders, Huntington’s disease, amyotrophic lateral sclerosis, and spinocerebellar ataxia in humans. We discuss the benefits and pitfalls of using this treatment approach within the spectrum of disease-modification efforts in neurodegenerative diseases. SCT may hold greater promise in the treatment of neurodegenerative disorders, but much research is required to determine the feasibility, safety, and efficacy of these complementary aims of therapeutic efforts. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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15 pages, 1845 KiB

Open AccessReview

Involvement of Intestinal Enteroendocrine Cells in Neurological and Psychiatric Disorders

by Liangen Yu and Yihang Li

Biomedicines 2022, 10(10), 2577; https://doi.org/10.3390/biomedicines10102577 - 14 Oct 2022

Cited by 7 | Viewed by 2822

Abstract

Neurological and psychiatric patients have increased dramatically in number in the past few decades. However, effective treatments for these diseases and disorders are limited due to heterogeneous and unclear pathogenic mechanisms. Therefore, further exploration of the biological aspects of the disease, and the [...] Read more.

Neurological and psychiatric patients have increased dramatically in number in the past few decades. However, effective treatments for these diseases and disorders are limited due to heterogeneous and unclear pathogenic mechanisms. Therefore, further exploration of the biological aspects of the disease, and the identification of novel targets to develop alternative treatment strategies, is urgently required. Systems-level investigations have indicated the potential involvement of the brain–gut axis and intestinal microbiota in the pathogenesis and regulation of neurological and psychiatric disorders. While intestinal microbiota is crucial for maintaining host physiology, some important sensory and regulatory cells in the host should not be overlooked. Intestinal epithelial enteroendocrine cells (EECs) residing in the epithelium throughout intestine are the key regulators orchestrating the communication along the brain-gut-microbiota axis. On one hand, EECs sense changes in luminal microorganisms via microbial metabolites; on the other hand, they communicate with host body systems via neuroendocrine molecules. Therefore, EECs are believed to play important roles in neurological and psychiatric disorders. This review highlights the involvement of EECs and subtype cells, via secretion of endocrine molecules, in the development and regulation of neurological and psychiatric disorders, including Parkinson’s disease (PD), schizophrenia, visceral pain, neuropathic pain, and depression. Moreover, the current paper summarizes the potential mechanism of EECs in contributing to disease pathogenesis. Examination of these mechanisms may inspire and lead to the development of new aspects of treatment strategies for neurological and psychiatric disorders in the future. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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16 pages, 974 KiB

Open AccessReview

New Insights into Cerebral Vessel Disease Landscapes at Single-Cell Resolution: Pathogenetic and Therapeutic Perspectives

by Megi Meneri, Sara Bonato, Delia Gagliardi, Giacomo P. Comi and Stefania Corti

Biomedicines 2022, 10(7), 1693; https://doi.org/10.3390/biomedicines10071693 - 13 Jul 2022

Cited by 1 | Viewed by 2654

Abstract

Cerebrovascular diseases are a leading cause of death and disability globally. The development of new therapeutic targets for cerebrovascular diseases (e.g., ischemic, and hemorrhagic stroke, vascular dementia) is limited by a lack of knowledge of the cellular and molecular biology of health and [...] Read more.

Cerebrovascular diseases are a leading cause of death and disability globally. The development of new therapeutic targets for cerebrovascular diseases (e.g., ischemic, and hemorrhagic stroke, vascular dementia) is limited by a lack of knowledge of the cellular and molecular biology of health and disease conditions and the factors that cause injury to cerebrovascular structures. Here, we describe the role of advances in omics technology, particularly RNA sequencing, in studying high-dimensional, multifaceted profiles of thousands of individual blood and vessel cells at single-cell resolution. This analysis enables the dissection of the heterogeneity of diseased cerebral vessels and their atherosclerotic plaques, including the microenvironment, cell evolutionary trajectory, and immune response pathway. In animal models, RNA sequencing permits the tracking of individual cells (including immunological, endothelial, and vascular smooth muscle cells) that compose atherosclerotic plaques and their alteration under experimental settings such as phenotypic transition. We describe how single-cell RNA transcriptomics in humans allows mapping to the molecular and cellular levels of atherosclerotic plaques in cerebral arteries, tracking individual lymphocytes and macrophages, and how these data can aid in identifying novel immune mechanisms that could be exploited as therapeutic targets for cerebrovascular diseases. Single-cell multi-omics approaches will likely provide the unprecedented resolution and depth of data needed to generate clinically relevant cellular and molecular signatures for the precise treatment of cerebrovascular diseases. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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15 pages, 788 KiB

Open AccessReview

Why Does Psychotherapy Work and for Whom? Hormonal Answers

by Susanne Fischer and Sigal Zilcha-Mano

Biomedicines 2022, 10(6), 1361; https://doi.org/10.3390/biomedicines10061361 - 9 Jun 2022

Cited by 9 | Viewed by 3659

Abstract

The questions of for whom and why psychotherapy is effective have been the focus of five decades of research. Most of this knowledge is based on self-report measures. Following the biopsychosocial model of mental disorders, this article explores the potential of hormones in [...] Read more.

The questions of for whom and why psychotherapy is effective have been the focus of five decades of research. Most of this knowledge is based on self-report measures. Following the biopsychosocial model of mental disorders, this article explores the potential of hormones in answering these questions. The literature on cortisol, oxytocin, and oestradiol in psychotherapy was systematically searched, focusing on (a) baseline hormonal predictors of who may benefit from psychotherapy and (b) hormonal changes as indicators of therapeutic change. The search was limited to depression and anxiety disorders. In sum, the findings show that, of all three hormones, the role of cortisol is most established and that both cortisol and oxytocin are implicated in psychotherapy, although a causal role is still waiting to be demonstrated. Moreover, there is a differential role of hormones in the psychotherapy of depression versus anxiety. The directions of research mapped in this article may elucidate how psychotherapy can be selected to match patients’ endocrine states and how hormonal levels can be manipulated to improve outcomes. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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Other

Jump to: Research, Review

9 pages, 526 KiB

Open AccessSystematic Review

Brain-Derived Neurotrophic Factor (BDNF) as an Indicator for Effects of Cognitive Behavioral Therapy (CBT): A Systematic Review

by Anna Mosiołek, Magdalena Pietrzak, Maria Tabisz, Wiktoria Wojtaszek, Michalina Zabielska, Agnieszka Ostrowska, Paweł Szwed, Jadwiga Mosiołek and Agata Szulc

Biomedicines 2023, 11(1), 27; https://doi.org/10.3390/biomedicines11010027 - 22 Dec 2022

Cited by 2 | Viewed by 1376

Abstract

Brain-derived neurotrophic factor (BDNF) is a protein affecting survival of existing neurons and neuronal maturation. Patients suffering from several mental disorders exhibit reduced BDNF levels comparing to healthy population. In this systematic review we aim to evaluate the effect of broadly defined cognitive [...] Read more.

Brain-derived neurotrophic factor (BDNF) is a protein affecting survival of existing neurons and neuronal maturation. Patients suffering from several mental disorders exhibit reduced BDNF levels comparing to healthy population. In this systematic review we aim to evaluate the effect of broadly defined cognitive behavioral therapy (CBT) on BDNF levels in psychiatric patients. A literature search was performed using PubMed and Google Scholar data bases. The resources were searched between 14 January and 3 February 2022. Following the inclusion criteria, a total of 10 randomized-controlled trials were included. The results of our research indicate that BDNF levels might be considered an indicator of a result achieved in psychotherapy of cognitive functions. However, no such correlation was observed for mindfulness-based practices intended to lower stress levels or improve the quality of life. It is important to notice that present research showed no consistent correlation between the increase in BDNF levels and the perceived effectiveness of the procedures. Thus, the exact role of BDNF remains unknown, and so far, it cannot be taken as an objective measure of the quality of the interventions. Full article

(This article belongs to the Special Issue Molecular Research in Neurological and Psychiatric Disease)

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