title: Improvement of Psychotic Symptoms and the Role of Tissue Plasminogen Activator.
abstract: Tissue plasminogen activator (tPA) mediates a number of processes that are pivotal for synaptogenesis and remodeling of synapses, including proteolysis of the brain extracellular matrix, degradation of adhesion molecules, activation of neurotrophins, and activation of the N-methyl-d-aspartate receptor. Abnormalities in these processes have been consistently described in psychotic disorders. In this paper, we review the physiological roles of tPA, focusing on conditions characterized by low tPA activity, which are prevalent in schizophrenia. We then describe how tPA activity is influenced by lifestyle interventions and nutritional supplements that may ameliorate psychotic symptoms. Next, we analyze the role of tPA in the mechanism of action of hormones and medications effective in mitigating psychotic symptoms, such as pregnenolone, estrogen, oxytocin, dopamine D3 receptor antagonists, retinoic acid, valproic acid, cannabidiol, sodium nitroprusside, N-acetyl cysteine, and warfarin. We also review evidence that tPA participates in the mechanism by which electroconvulsive therapy and cigarette smoking may reduce psychotic symptoms.
authors.affiliation: Department of Hematology, Hospital Federal dos Servidores do Estado, Ministry of Health, Rio de Janeiro CEP 20221-903, Brazil. sclapauch@ig.com.br.
authors.forename: Silvia
authors.initials: S
authors.lastname: Hoirisch-Clapauch
authors.affiliation: Institute of Psychiatry, Federal University of Rio de Janeiro, and National Institute for Translational Medicine, INCT-TM CEP 22290-140, Brazil. antonioenardi@gmail.com.
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Nardi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D019587:Dietary Supplements; D004565:Electroconvulsive Therapy; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008019:Life Style; D009479:Neuropeptides / Q000378:metabolism; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011485:Protein Binding; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D012559:Schizophrenia / Q000175:diagnosis / Q000178:diet therapy / Q000378:metabolism / Q000628:therapy; D015843:Serpins / Q000378:metabolism; D012907:Smoking; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097522:Neuroserpin
chemical_list: D014150:Antipsychotic Agents; D006728:Hormones; D009479:Neuropeptides; D017395:Plasminogen Activator Inhibitor 1; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin
keywords: cognition; refractory; resistant; schizophrenia; tissue plasminogen activator