Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders

Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies

Assessment of DDAH1 and DDAH2 Contributions to Psychiatric Disorders via In Silico Methods

The contribution of nitric oxide synthases (NOSs) to the pathophysiology of several neuropsychiatric disorders is recognized, but the role of their regulators, dimethylarginine dimethylaminohydrolases (DDAHs), is less understood. This study’s objective was to estimate DDAH1 and DDAH2 associations with biological processes implicated in major psychiatric disorders using publicly accessible expression databases. Since co-expressed genes are more likely to be involved in the same biologic processes, we investigated co-expression patterns with DDAH1 and DDAH2 in the dorsolateral prefrontal cortex in psychiatric patients and control subjects. There were no significant differences in DDAH1 and DDAH2 expression levels in schizophrenia or bipolar disorder patients compared to controls. Meanwhile, the data suggest that in patients, DDAH1 and DDHA2 undergo a functional shift mirrored in changes in co-expressed gene patterns. This disarrangement appears in the loss of expression level correlations between DDAH1 or DDAH2 and genes associated with psychiatric disorders and reduced functional similarity of DDAH1 or DDAH2 co-expressed genes in the patient groups. Our findings evidence the possible involvement of DDAH1 and DDAH2 in neuropsychiatric disorder development, but the underlying mechanisms need experimental validation

Metagenomic profiling of viral and microbial communities from the pox lesions of lumpy skin disease virus and sheeppox virus-infected hosts

IntroductionIt has been recognized that capripoxvirus infections have a strong cutaneous tropism with the manifestation of skin lesions in the form of nodules and scabs in the respective hosts, followed by necrosis and sloughing off. Considering that the skin microbiota is a complex community of commensal bacteria, fungi and viruses that are influenced by infections leading to pathological states, there is no evidence on how the skin microbiome is affected during capripoxvirus pathogenesis.MethodsIn this study, shotgun metagenomic sequencing was used to investigate the microbiome in pox lesions from hosts infected with lumpy skin disease virus and sheep pox virus.ResultsThe analysis revealed a high degree of variability in bacterial community structures across affected skin samples, indicating the importance of specific commensal microorganisms colonizing individual hosts. The most common and abundant bacteria found in scab samples were Fusobacterium necrophorum, Streptococcus dysgalactiae, Helcococcus ovis and Trueperella pyogenes, irrespective of host. Bacterial reads belonging to the genera Moraxella, Mannheimia, Corynebacterium, Staphylococcus and Micrococcus were identified.DiscussionThis study is the first to investigate capripox virus-associated changes in the skin microbiome using whole-genome metagenomic profiling. The findings will provide a basis for further investigation into capripoxvirus pathogenesis. In addition, this study highlights the challenge of selecting an optimal bioinformatics approach for the analysis of metagenomic data in clinical and veterinary practice. For example, direct classification of reads using a kmer-based algorithm resulted in a significant number of systematic false positives, which may be attributed to the peculiarities of the algorithm and database selection. On the contrary, the process of de novo assembly requires a large number of target reads from the symbiotic microbial community. In this work, the obtained sequencing data were processed by three different approaches, including direct classification of reads based on k-mers, mapping of reads to a marker gene database, and de novo assembly and binning of metagenomic contigs. The advantages and disadvantages of these techniques and their practicality in veterinary settings are discussed in relation to the results obtained

Cognitive Training as a Potential Activator of Hippocampal Neurogenesis in the Rat Model of Sporadic Alzheimer’s Disease

There is a growing body of evidence that interventions like cognitive training or exercises prior to the manifestation of Alzheimer’s disease (AD) symptoms may decelerate cognitive decline. Nonetheless, evidence of prevention or a delay of dementia is still insufficient. Using OXYS rats as a suitable model of sporadic AD and Wistar rats as a control, we examined effects of cognitive training in the Morris water maze on neurogenesis in the dentate gyrus in presymptomatic (young rats) and symptomatic (adult rats) periods of development of AD signs. Four weeks after the cognitive training, we immunohistochemically estimated densities of quiescent and amplifying neuronal progenitors, neuronal-lineage cells (neuroblasts and immature and mature neurons), and astrocytes in young and adult rats, and the amyloid precursor protein and amyloid-β in adult rats. Reference memory was defective in OXYS rats. The cognitive training did not affect neuronal-lineage cells’ density in either rat strain either at the young or adult age, but activated neuronal progenitors in young rats and increased astrocyte density and downregulated amyloid-β in adult OXYS rats. Thus, to activate adult neurogenesis, cognitive training should be started before first neurodegenerative changes, whereas cognitive training accompanying amyloid-β accumulation affects only astrocytic support

Assessment of DDAH1 and DDAH2 Contributions to Psychiatric Disorders via In Silico Methods

The contribution of nitric oxide synthases (NOSs) to the pathophysiology of several neuropsychiatric disorders is recognized, but the role of their regulators, dimethylarginine dimethylaminohydrolases (DDAHs), is less understood. This study’s objective was to estimate DDAH1 and DDAH2 associations with biological processes implicated in major psychiatric disorders using publicly accessible expression databases. Since co-expressed genes are more likely to be involved in the same biologic processes, we investigated co-expression patterns with DDAH1 and DDAH2 in the dorsolateral prefrontal cortex in psychiatric patients and control subjects. There were no significant differences in DDAH1 and DDAH2 expression levels in schizophrenia or bipolar disorder patients compared to controls. Meanwhile, the data suggest that in patients, DDAH1 and DDHA2 undergo a functional shift mirrored in changes in co-expressed gene patterns. This disarrangement appears in the loss of expression level correlations between DDAH1 or DDAH2 and genes associated with psychiatric disorders and reduced functional similarity of DDAH1 or DDAH2 co-expressed genes in the patient groups. Our findings evidence the possible involvement of DDAH1 and DDAH2 in neuropsychiatric disorder development, but the underlying mechanisms need experimental validation

Changes in Glial Support of the Hippocampus during the Development of an Alzheimer’s Disease-like Pathology and Their Correction by Mitochondria-Targeted Antioxidant SkQ1

Astrocytes and microglia are the first cells to react to neurodegeneration, e.g., in Alzheimer’s disease (AD); however, the data on changes in glial support during the most common (sporadic) type of the disease are sparse. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, and Wistar rats (parental normal strain, control), we investigated hippocampal neurogenesis and glial changes during AD-like pathology. Using immunohistochemistry, we showed that the early stage of the pathology is accompanied by a lower intensity of neurogenesis and decreased astrocyte density in the dentate gyrus. The progressive stage is concurrent with reactive astrogliosis and microglia activation, as confirmed by increased cell densities and by the acquisition of cell-specific gene expression profiles, according to transcriptome sequencing data. Besides, here, we continued to analyze the anti-AD effects of prolonged supplementation with mitochondria-targeted antioxidant SkQ1. The antioxidant did not affect neurogenesis, partly normalized the gene expression profile of astrocytes and microglia, and shifted the resting/activated microglia ratio toward a decrease in the activated-cell density. In summary, both astrocytes and microglia are more vulnerable to AD-associated neurodegeneration in the CA3 area than in other hippocampal areas; SkQ1 had an anti-inflammatory effect and is a promising modality for AD prevention and treatment

Клинический случай высокой коморбидности у недоношенного ребенка — тромбоз брюшного отдела аорты, синдром Вольфа – Паркинсона – Уайта, приобретенный гипотиреоз

Background. Neonatal thromboses, both venous and arterial, are a rare pathology, and experience in systemic thrombolysis is very low. Thus, the methods of adult management are currently being adapted to pediatric practice.Clinical case description. This report describes clinical case of abdominal aortic thrombosis in a premature infant with later diagnosed Wolff-ParkinsonWhite syndrome and acquired hypothyroidism developed due to antiarrhythmic therapy.Conclusion. The premature boy had high comorbidity that required many specialists’ involvement. Timely systemic thrombolytic therapy and antiarrhythmic drugs selection made it possible to save the child's life and most likely to avoid disability in the future. Обоснование. Неонатальные тромбозы, как венозные, так и артериальные, являются редкой патологией, опыт проведения системного тромболизиса немногочислен. В связи с этим в настоящее время проводится адаптация методов терапии взрослых к детской практике.Описание клинического случая. В представленном сообщении описан клинический случай тромбоза брюшного отдела аорты у недоношенного ребенка с впоследствии выявленным синдромом Вольфа – Паркинсона – Уайта и приобретенным гипотиреозом, возникшим на фоне антиаритмической терапии.Заключение. У недоношенного мальчика отмечалась высокая коморбидность, которая потребовала участия многих специалистов. Своевременное проведение системной тромболитической терапии и подбор противоаритмических препаратов позволили сохранить ребенку жизнь и с большой долей вероятности избежать инвалидизации в дальнейшем.

Trace Amine-Associated Receptor 5 Provides Olfactory Input Into Limbic Brain Areas and Modulates Emotional Behaviors and Serotonin Transmission

Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other TAARs have been described mainly in the olfactory epithelium and the glomerular layer of the olfactory bulb and are believed to serve as a new class of olfactory receptors sensing innate odors. However, there is evidence that TAAR5 could play a role also in the central nervous system. In this study, we characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO) expressing beta-galactosidase mapping TAAR5 expression. We found that TAAR5 is expressed not only in the glomerular layer in the olfactory bulb but also in deeper layers projecting to the limbic brain olfactory circuitry with prominent expression in numerous limbic brain regions, such as the anterior olfactory nucleus, the olfactory tubercle, the orbitofrontal cortex (OFC), the amygdala, the hippocampus, the piriform cortex, the entorhinal cortex, the nucleus accumbens, and the thalamic and hypothalamic nuclei. TAAR5-KO mice did not show gross developmental abnormalities but demonstrated less anxiety- and depressive-like behavior in several behavioral tests. TAAR5-KO mice also showed significant decreases in the tissue levels of serotonin and its metabolite in several brain areas and were more sensitive to the hypothermic action of serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di- n -propilamino)tetralin (8-OH-DPAT). These observations indicate that TAAR5 is not just innate odor-sensing olfactory receptor but also serves to provide olfactory input into limbic brain areas to regulate emotional behaviors likely via modulation of the serotonin system. Thus, anxiolytic and/or antidepressant action of future TAAR5 antagonists could be predicted. In general, “olfactory” TAAR-mediated brain circuitry may represent a previously unappreciated neurotransmitter system involved in the transmission of innate odors into emotional behavioral responses