DIFFERENTIAL DIAGNOSIS OF RADICULOPATHY IN LYME BORRELIOSISAND DYSTROPHIC LESIONS OF THE VERTEBRAL COLUMN

Subjects and methods. Thirty patients, including 9 (30.0%) men and 21 (70.0%) women, with signs of radiculopathy (RP) in late-stages Lyme borreliosis (LB) were examined. A control group comprised 30 patients with vertebrogenic RP in the presence of dystrophic changes in the vertebral column. Results. 56.7% of the patients with LB were observed to have its primary chronic course in the absence of the acute period of LB. The latter with the signs of RP showed a topic association between the pain location and the tick bite site in 43.3% of the patients. A gradual disease development was more frequently (63.3%) observed in LB while the periods of remission and exacerbation were more typical (56.7%) in vertebrogenic RP. In the patients with LB, pain syndrome depended on posture and physical exercise less frequently (30.0%) than in those with vertebrogenic RP (96.7%). Bilateral pain irradiation was more characteristic of RP in LB than in dystrophic lesions of the vertebral column. The symptoms of tonic muscle tension and limited movement volume in the afflicted part of the vertebral column were significantly less common in the patients with LB than in those with vertebrogenic RP. LB was marked by a concomitance of radicular and polyneuritic disorders (83.3%) and vertebrogenic RP was characterized by a preponderance of the radicular-type of sensitivity disorder (100%). Systemic inflammatory syndrome and polysystemacy of manifestations were more characteristic of LB. The benefits of nonsteriodal antiinflammatory drugs in LB patients with RP were significantly worse than in those with vertebrogenic RP; regression of symptoms in LB was seen only after a course of specific antibiotic therapy

Evolutionarily conserved gene expression patterns for affective disorders revealed using cross-species brain transcriptomic analyses in humans, rats and zebrafish

Abstract Widespread, debilitating and often treatment-resistant, depression and other stress-related neuropsychiatric disorders represent an urgent unmet biomedical and societal problem. Although animal models of these disorders are commonly used to study stress pathogenesis, they are often difficult to translate across species into valuable and meaningful clinically relevant data. To address this problem, here we utilized several cross-species/cross-taxon approaches to identify potential evolutionarily conserved differentially expressed genes and their sets. We also assessed enrichment of these genes for transcription factors DNA-binding sites down- and up- stream from their genetic sequences. For this, we compared our own RNA-seq brain transcriptomic data obtained from chronically stressed rats and zebrafish with publicly available human transcriptomic data for patients with major depression and their respective healthy control groups. Utilizing these data from the three species, we next analyzed their differential gene expression, gene set enrichment and protein–protein interaction networks, combined with validated tools for data pooling. This approach allowed us to identify several key brain proteins (GRIA1, DLG1, CDH1, THRB, PLCG2, NGEF, IKZF1 and FEZF2) as promising, evolutionarily conserved and shared affective ‘hub’ protein targets, as well as to propose a novel gene set that may be used to further study affective pathogenesis. Overall, these approaches may advance cross-species brain transcriptomic analyses, and call for further cross-species studies into putative shared molecular mechanisms of affective pathogenesis

Acute behavioral and Neurochemical Effects of Novel N-Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish

Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH3, -OCF3, -F, -Cl, and -Br substitutions in the ortho position of the phenyl ring of the N-benzyl moiety, assessing their acute behavioral and neurochemical effects in the adult zebrafish. Overall, substitutions in the Overall, substitutions in the N-benzyl moiety modulate locomotion, and substitutions in the phenethylamine moiety alter zebrafish anxiety-like behavior, also affecting the brain serotonin and/or dopamine turnover. The 24H-NBOMe(F) and 34H-NBOMe(F) treatment also reduced zebrafish despair-like behavior. Computational analyses of zebrafish behavioral data by artificial intelligence identified several distinct clusters for these agents, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe, and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl, and 34H-NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl, and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) drugs. Our computational analyses also revealed phenotypic similarity of the behavioral activity of some NBPEAs to that of selected conventional serotonergic and antiglutamatergic hallucinogens. In silico functional molecular activity modeling further supported the overlap of the drug targets for NBPEAs tested here and the conventional serotonergic and antiglutamatergic hallucinogens. Overall, these findings suggest potent neuroactive properties of several novel synthetic NBPEAs, detected in a sensitive in vivo vertebrate model system, the zebrafish, raising the possibility of their potential clinical use and abuse