Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host’s eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018–2022) and identified twenty two eligible cases, restricted only to human patients’ experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains

first_page settings Order Article Reprints Open AccessArticle Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains by Ovidiu-Dumitru Ilie 1,† [ORCID] , Raluca Duta 1, Ioana-Miruna Balmus 2,3, Alexandra Savuca 4 [ORCID] , Adriana Petrovici 5 [ORCID] , Ilinca-Bianca Nita 6, Lucian-Mihai Antoci 7, Roxana Jijie 8,† [ORCID] , Cosmin-Teodor Mihai 9 [ORCID] , Alin Ciobica 1,*, Mircea Nicoara 1,4 [ORCID] , Roxana Popescu 7,10 [ORCID] , Romeo Dobrin 11,* [ORCID] , Carmen Solcan 5,* [ORCID] , Anca Trifan 12,13 [ORCID] , Carol Stanciu 12,13 and Bogdan Doroftei 6 [ORCID] 1 Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 2 Department of Exact and Natural Sciences, Institute of Interdisciplinary Research, “Alexandru Ioan Cuza” University, Carol I Avenue, no 11, 700506 Iasi, Romania 3 Doctoral School of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, 20A, 700506 Iasi, Romania 4 Doctoral School of Geosciences, Faculty of Geography-Geology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 5 Department of Molecular Biology, Histology and Embryology, Faculty of Veterinary Medicine, University of Life Sciences “Ion Ionescu de la Brad”, Mihail Sadoveanu Street, no 3, 700490 Iasi, Romania 6 Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 7 Department of Medical Genetics, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 8 Research Center on Advanced Materials and Technologies, Department of Exact and Natural Sciences, Institute of Inderdisciplinary Research, “Alexandru Ioan Cuza” University, Carol I Avenue, no 11, 700506 Iasi, Romania 9 Advanced Research and Development Center for Experimental Medicine (CEMEX), University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 10 Department of Medical Genetics, “Saint Mary” Emergency Children’s Hospital, Vasile Lupu Street, no 62, 700309 Iasi, Romania add Show full affiliation list * Authors to whom correspondence should be addressed. † These authors equally contributed to this work. Antioxidants 2022, 11(10), 2040; https://doi.org/10.3390/antiox11102040 Received: 2 September 2022 / Revised: 3 October 2022 / Accepted: 13 October 2022 / Published: 17 October 2022 (This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurological and Neurodegenerative Disorders) Download Browse Figures Review Reports Versions Notes Abstract Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio