Volume 35, Issue 1

Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, by repetitive behavior, and often anxiety and learning disabilities. The brain serotonin (5-HT) system is known to be crucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for in vivo regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter in the mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT–related drugs have potential for ASD treatment.

Neuropsychiatric disorders (NPDs) are considered a potential threat to mental health. Inflammation predominantly plays a role in the pathophysiology of NPDs. Dietary patterns are widely postulated to be involved in the physiological response to inflammation. This review aims to discuss the literature on how dietary inflammatory index (DII) is related to inflammation and, consequently, NPDs. After comprehensive scrutiny in different databases, the articles that investigated the relation of DII score and various NPDs and psychological circumstances were included. The association between dietary patterns and mental disorders comprising depression, anxiety, and stress proved the role of a proinflammatory diet in these conditions’ exacerbation. Aging is another condition closely associated with DII. The impact of proinflammatory and anti-inflammatory diet on sleep quality indicated related disorders like sleep latency and day dysfunctions among the different populations are in relation with the high DII score. The potential effects of genetic backgrounds, dietary patterns, and the gut microbiome on DII are discussed as well. To plan preventive or therapeutic interventions considering the DII, these factors, especially genetic variations, should be considered as there is a growing body of literature indicating the role of personalized medicine in different NPDs. To the best of our knowledge, there is a limited number of RCTs on this subject, so future research should evaluate the causality via RCTs and look for therapeutic interventions with an eye on personalized medicine using information about DII in NPDs.

Integrating individual actions into coherent, organised behavioural units, a process called chunking, is a fundamental, evolutionarily conserved process that renders actions automatic. In vertebrates, evidence points to the basal ganglia – a complex network believed to be involved in action selection – as a key component of action sequence encoding, although the underlying mechanisms are only just beginning to be understood. Central pattern generators control many innate automatic behavioural sequences that form some of the most basic behaviours in an animal’s repertoire, and in vertebrates, brainstem and spinal pattern generators are under the control of higher order structures such as the basal ganglia. Evidence suggests that the basal ganglia play a crucial role in the concatenation of simpler behaviours into more complex chunks, in the context of innate behavioural sequences such as chain grooming in rats, as well as sequences in which innate capabilities and learning interact such as birdsong, and sequences that are learned from scratch, such as lever press sequences in operant behaviour. It has been proposed that the role of the striatum, the largest input structure of the basal ganglia, might lie in selecting and allowing the relevant central pattern generators to gain access to the motor system in the correct order, while inhibiting other behaviours. As behaviours become more complex and flexible, the pattern generators seem to become more dependent on descending signals. Indeed, during learning, the striatum itself may adopt the functional characteristics of a higher order pattern generator, facilitated at the microcircuit level by striatal neuropeptides.

Late in the twentieth century, interest intensified regarding the involvement of the circadian system in the aetiology and treatment of Parkinson’s disease (PD). It has been envisaged that this approach might provide relief beyond the limited benefits and severe side effects achieved by dopamine (DA) replacement. In the first clinical article, published in 1996, polychromatic light was used to shift the circadian clock as it is considered to be the most powerful zeitgeber (time keeper) that can be implemented to realign circadian phase. Since that time, 11 additional articles have implemented light treatment (LT) in various forms as an adjuvant to DA replacement. In spite of the growing interest in this area, the systematic exploration of LT in PD has been stymied by several methodological factors. Such factors include time of LT presentation, duration of studies undertaken, frequency of light employed, dose of light prescribed and relevance of experimental design to the prolonged course of the illness. On this basis, it is the purpose of this review to provide an in-depth examination of these papers, and the underlying preclinical work, to provide critique, thereby giving direction for future studies in therapeutic applications of LT for PD. Consideration of this collective work may serve to carve a path for future research and thereby improve the lives of those suffering from this debilitating disorder.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. Mutations in C9orf72 and the resulting hexanucleotide repeat (GGGGCC) expansion (HRE) has been identified as a major cause of familial ALS, accounting for about 40 % of familial and 6 % of sporadic cases of ALS in Western patients. The pathological outcomes of HRE expansion in ALS have been recognized as the results of two mechanisms that include both the toxic gain-of-function and loss-of-function of C9ORF72. The gain of toxicity results from RNA and dipeptide repeats (DPRs). The HRE can be bidirectionally transcribed into RNA foci, which can bind to and disrupt RNA splicing, transport, and translation. The DPRs that include poly-glycine-alanine, poly-glycine-proline, poly-glycine- arginine, poly-proline-alanine, and poly-proline-arginine can induce toxicity by direct binding and sequestrating other proteins to interfere rRNA synthesis, ribosome biogenesis, translation, and nucleocytoplasmic transport. The C9ORF72 functions through binding to its partners-Smith-Magenis chromosome regions 8 (SMCR8) and WD repeat-containing protein (WDR41). Loss of C9ORF72 function results in impairment of autophagy, deregulation of autoimmunity, increased stress, and disruption of nucleocytoplasmic transport. Further insight into the mechanism in C9ORF72 HRE pathogenesis will facilitate identifying novel and effective therapeutic targets for ALS.

Peripheral inflammation could constitute a risk factor for AD. This review summarizes the research related to peripheral inflammation that appears to have a relationship with Alzheimer’s disease. We find there are significant associations between AD and peripheral infection induced by various pathogens, including herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Porphyromonas gingivalis , Helicobacter pylori , and Toxoplasma gondii . Chronic inflammatory diseases are also reported to contribute to the pathophysiology of AD. The mechanisms by which peripheral inflammation affects the pathophysiology of AD are complex. Pathogen-derived neurotoxic molecule composition, disrupted BBB, and dysfunctional neurogenesis may all play a role in peripheral inflammation, promoting the development of AD. Anti-pathogenic medications and anti-inflammatory treatments are reported to decrease the risk of AD. Studies that could improve understanding the associations between AD and peripheral inflammation are needed. If our assumption is correct, early intervention against inflammation may be a potential method of preventing and treating AD.