A healthy gut for a healthy brain: preclinical, clinical and regulatory aspects

: A large body of research has shown the presence of a complex pathway of communications between the gut and the brain. It is now recognized that, through this pathway, the microbiota can influence brain homeostasis and plasticity under normal and pathological conditions. This review aims at providing an overview of preclinical and clinical pieces of evidence supporting the possible role of gutbrain axis modulation in physiological aging, in a neurodevelopmental disorder, the autism spectrum disorders and in a substance abuse disorder, the alcohol addiction. Since the normalization of gut flora can prevent changes in the behavior, we postulate that the gut-brain axis might represent a possible target for pharmacological and dietary strategies aimed at improving not only intestinal but also mental health. The present review also reports some regulatory considerations regarding the use of probiotics, illustrating the most debated issues about the possibility of considering probiotics not only as a food supplement but also as a “full” medicinal product.

Download Full-text

FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-021-09358-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Reymundo Lozano ◽

Catherine Gbekie ◽

Paige M. Siper ◽

Shubhika Srivastava ◽

Jeffrey M. Saland ◽

...

Keyword(s):

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Medical Assessment ◽

Forkhead Box ◽

Organ Systems ◽

Practice Parameters ◽

Assessment And Monitoring ◽

Multidisciplinary Group ◽

The Brain

AbstractFOXP1 syndrome is a neurodevelopmental disorder caused by mutations or deletions that disrupt the forkhead box protein 1 (FOXP1) gene, which encodes a transcription factor important for the early development of many organ systems, including the brain. Numerous clinical studies have elucidated the role of FOXP1 in neurodevelopment and have characterized a phenotype. FOXP1 syndrome is associated with intellectual disability, language deficits, autism spectrum disorder, hypotonia, and congenital anomalies, including mild dysmorphic features, and brain, cardiac, and urogenital abnormalities. Here, we present a review of human studies summarizing the clinical features of individuals with FOXP1 syndrome and enlist a multidisciplinary group of clinicians (pediatrics, genetics, psychiatry, neurology, cardiology, endocrinology, nephrology, and psychology) to provide recommendations for the assessment of FOXP1 syndrome.

Download Full-text

The Role of Iron in the Pathogenesis of Autism Spectrum Disorders in Children

Вопросы современной педиатрии ◽

10.15690/vsp.v17i4.1920 ◽

2018 ◽

Vol 17 (4) ◽

pp. 281-286 ◽

Cited By ~ 1

Author(s):

Olga V. Kostina

Keyword(s):

Autism Spectrum Disorders ◽

Iron Metabolism ◽

Biochemical Parameters ◽

Children With Autism ◽

Neuropsychiatric Disorders ◽

Perinatal Period ◽

Autism Spectrum ◽

Spectrum Disorders ◽

The Brain

The review presents an analysis of the mechanisms of iron effect on the brain development. The importance of iron deficiency in the perinatal period is considered as a risk factor for the development of neuropsychiatric disorders in children with autism spectrum disorders (ASDs). Possible causes of sideropenia are discussed; data on haematological and biochemical parameters characterizing iron metabolism in children with ASDs are presented. The demand for studying the role of iron metabolism imbalance in the development of neuropsychiatric disorders in order to clarify pathogenetic mechanisms of ASDs and to determine methods for their correction is emphasized.

Download Full-text

The epigenetic regulation of synaptic genes contributes to the etiology of autism

Reviews in the Neurosciences ◽

10.1515/revneuro-2021-0014 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Annamaria Srancikova ◽

Zuzana Bacova ◽

Jan Bakos

Keyword(s):

Epigenetic Regulation ◽

Neurodevelopmental Disorders ◽

Autism Spectrum ◽

Prader Willi Syndrome ◽

Epigenetic Mechanisms ◽

Substantial Evidence ◽

Autistic Symptoms ◽

Spectrum Disorders ◽

The Brain

Abstract Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.

Download Full-text

Pathogenetical and Neurophysiological Features of Patients with Autism Spectrum Disorder: Phenomena and Diagnoses

Journal of Clinical Medicine ◽

10.3390/jcm8101588 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1588

Author(s):

Yunho Jin ◽

Jeonghyun Choi ◽

Seunghoon Lee ◽

Jong Won Kim ◽

Yonggeun Hong

Keyword(s):

Autism Spectrum Disorder ◽

Neural Development ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Deficits ◽

Restricted Interests ◽

Neuropsychiatric Comorbidities ◽

The Brain

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is accompanied by social deficits, repetitive and restricted interests, and altered brain development. The majority of ASD patients suffer not only from ASD itself but also from its neuropsychiatric comorbidities. Alterations in brain structure, synaptic development, and misregulation of neuroinflammation are considered risk factors for ASD and neuropsychiatric comorbidities. Electroencephalography has been developed to quantitatively explore effects of these neuronal changes of the brain in ASD. The pineal neurohormone melatonin is able to contribute to neural development. Also, this hormone has an inflammation-regulatory role and acts as a circadian key regulator to normalize sleep. These functions of melatonin may play crucial roles in the alleviation of ASD and its neuropsychiatric comorbidities. In this context, this article focuses on the presumable role of melatonin and suggests that this hormone could be a therapeutic agent for ASD and its related neuropsychiatric disorders.

Download Full-text

Essential role of the nuclear isoform of RBFOX1, a candidate gene for autism spectrum disorders, in the brain development

Scientific Reports ◽

10.1038/srep30805 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 33

Author(s):

Nanako Hamada ◽

Hidenori Ito ◽

Takuma Nishijo ◽

Ikuko Iwamoto ◽

Rika Morishita ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Brain Development ◽

Candidate Gene ◽

Essential Role ◽

Autism Spectrum ◽

Spectrum Disorders ◽

The Brain

Download Full-text

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

Journal of Clinical Medicine ◽

10.3390/jcm10112358 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2358

Author(s):

Maria Grazia Giovannini ◽

Daniele Lana ◽

Chiara Traini ◽

Maria Giuliana Vannucchi

Keyword(s):

Alzheimer Disease ◽

Glial Cells ◽

Cell Types ◽

The Past ◽

The Central Nervous System ◽

Diseased State ◽

The Brain ◽

Alzheimer Disease Pathogenesis ◽

Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

Download Full-text

LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

Science Advances ◽

10.1126/sciadv.aba1187 ◽

2021 ◽

Vol 7 (11) ◽

pp. eaba1187

Author(s):

Rina Baba ◽

Satoru Matsuda ◽

Yuuichi Arakawa ◽

Ryuji Yamada ◽

Noriko Suzuki ◽

...

Keyword(s):

Gene Expression ◽

Enzyme Activity ◽

Neurodevelopmental Disorders ◽

Neurodevelopmental Disorder ◽

Specific Inhibitor ◽

Autism Spectrum ◽

Poly I:C ◽

Control Of Gene Expression ◽

Epigenetic Machinery ◽

The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

Download Full-text