Alterations in Serotonin Neurotransmission in Hyperdopaminergic Rats Lacking the Dopamine Transporter.

Biogenic amines dopamine (DA) and serotonin (5-HT) are among the most significant monoaminergic neurotransmitters in the central nervous system (CNS). Separately, the physiological roles of DA and 5-HT have been studied in detail, and progress has been made in understanding their roles in normal and various pathological conditions (Parkinson's disease, schizophrenia, addiction, depression, etc.). In this article we showed that knockout of the gene encoding DAT leads not only to a profound dysregulation of dopamine neurotransmission in the striatum but also in the midbrain, prefrontal cortex, hippocampus, medulla oblongata and spinal cord. Furthermore, significant changes were observed in the production of mRNA of enzymes of monoamine metabolism, as well as to a notable alteration in the tissue level of serotonin, most clearly manifested in the cerebellum and the spinal cord. The observed region-specific changes in the tissue levels of serotonin and in the expression of dopamine and serotonergic metabolism enzymes in rats with an excess of dopamine can indicate important consequences for the pharmacotherapy of drugs that modulate the dopaminergic system. The drugs that affect the dopaminergic system could potently affect the serotonergic system, and this fact is important to consider when predicting their possible therapeutic or side effects.

Limited Cheese Intake Paradigm Replaces Patterns of Behavioral Disorders in Experimental PTSD: Focus on Resveratrol Supplementation.

Currently, the efficacy of drug therapy for post-traumatic stress disorder or PTSD leaves much to be desired, making nutraceutical support a promising avenue for treatment. Recent research has identified the protective effects of resveratrol in PTSD. Here, we tested the behavioral and neurobiological effects of combining cheese consumption with resveratrol supplements in an experimental PTSD model. Using the elevated plus maze test, we observed that cheese intake resulted in a shift from anxiety-like behavior to depressive behavior, evident in increased freezing acts. However, no significant changes in the anxiety index value were observed. Interestingly, supplementation with cheese and resveratrol only led to the elimination of freezing behavior in half of the PTSD rats. We further segregated the rats into two groups based on freezing behavior: Freezing+ and Freezing0 phenotypes. Resveratrol ameliorated the abnormalities in Monoamine Oxidize -A and Brain-Derived Neurotrophic Factor gene expression in the hippocampus, but only in the Freezing0 rats. Moreover, a negative correlation was found between the number of freezing acts and the levels of Monoamine Oxidize-A and Brain-Derived Neurotrophic Factor mRNAs in the hippocampus. The study results show promise for resveratrol supplementation in PTSD treatment. Further research is warranted to better understand the underlying mechanisms and optimize the potential benefits of resveratrol supplementation for PTSD.

Functions and distribution of calpain-calpastatin system components in brain during mammal ontogeny.

Calpain and calpastatin are the key components of the calcium-dependent proteolytic system. Calpains are regulatory, calcium-dependent, cytoplasmic proteinases, and calpastatin is the endogenous inhibitor of calpains. Due to the correlation between changes in the activity of the calpain-calpastatin system in the brain and central nervous system (CNS) pathology states, this proteolytic system is a prime focus of research on CNS pathological processes, generally characterized by calpain activity upregulation. The present review aims to generalize existing data on cerebral calpain distribution and function through mammalian ontogenesis. Special attention is given to the most recent studies on the topic as more information on calpain-calpastatin system involvement in normal CNS development and functioning has become available. We also discuss data on calpain and calpastatin activity and production in different brain regions during ontogenesis as comparative analysis of these results in association with ontogeny processes can reveal brain regions and developmental stages with pronounced function of the calpain system.

Neurotensin-Binding Immunoglobulin G in Patients with Parkinson's Disease.

INTRODUCTION: Neurotensin (NTS) is a 13-amino acid neuropeptide functionally linked with the brain dopaminergic system via expression of the NTS peptide or its receptor in dopamine neurons. Neuropeptide-binding immunoglobulins (Igs) are present in humans and can be involved in both physiological and pathological processes. Considering the functional link between NTS and dopamine neurons, we studied the occurrence of NTS-binding IgG autoantibodies in patients with Parkinson's disease (PD). METHODS: Plasma levels of NTS-binding IgG were analyzed using enzyme-linked immunosorbent assay in both male and female PD patents and in age-matched healthy controls. Possible microbial origin of NTS cross-reactive IgG was analyzed by sequence alignment of the 6-amino acid C-terminal NTS pharmacophore with bacterial and viral proteins from the public NCBI database. RESULTS: NTS-binding IgG were detected in the plasma of all study subjects, while their levels were consistently lower in PD patients versus controls (p = 0.0001), independently from age or sex of the study participants. Moreover, PD patients with a more severe stage (2.5-3.0) of the disease had lower levels of NTS-binding IgG (p = 0.0004) than those with a milder stage (1.0-2.0). Furthermore, PD patients taking amantadine or high doses of levodopa had higher levels of NTS-binding IgG than those without medication. Contiguous sequence homology for the NTS pharmacophore was present in several microbial proteins occurring in human gut microbiota. DISCUSSION: The study revealed that NTS-binding IgG occur naturally in humans and that PD patients display their low plasma levels accentuated by disease severity. The functional significance of this finding and its relevance to the pathophysiology of PD, including putative link to gut microbiota, remain to be studied.

Cluster analysis of clinical, biochemical and electrophysiological features of essential tremor patients. Exploratory study.

BACKGROUND: Essential tremor (ET) is one of the most common movement disorders. The clinical heterogeneity of ET has been studied for many years, however, there are practically no comprehensive studies dedicated to the assessment of biochemical and electrophysiological parameters associated with the severity of motor and non-motor disorders present in patients with ET and taking into account their heterogeneity. OBJECTIVES: The objective of this report is to differentiate subgroups of essential tremor using cluster analysis of clinical, biochemical and electrophysiological parameters. METHODS: The study enrolled 90 patients with ET. Clustering was perform on the demographic data, scores of scales FTMS, ADL, MoCA, Beka, surface electromyographic data, levels of serum IL-1ß, IL-6, IL-8, IL-10, TNFα, uric acid, ceruloplasmin, MDA. RESULTS: Based on the analysis of the severity of motor manifestations, the psychoemotional state, the adaptive potential of patients and the biochemical aspects of the pathogenesis, three relatively homogeneous clusters of ET were identified. CONCLUSIONS: Revealing the heterogeneity of essential tremor allows to expand understanding the pathogenesis of disease.