Person: Leza Cerro, Juan Carlos
Loading...
First Name
Juan Carlos
Last Name
Leza Cerro
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Farmacología y Toxicología
Area
Farmacología
Identifiers
32 results
Search Results
Now showing 1 - 10 of 32
Item Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation(International Journal of Neuropsychopharmacology, 2013) Mac-Dowell Mata, Karina Soledad; García Bueno, Borja; Muñoz Madrigal, José Luis; Parellada, Mara; Arango López, Celso; Micó, Juan A.; Leza Cerro, Juan Carlos; Parellada Redondo, María JoséInflammation, caused by both external and endogenous factors, has been implicated as a main pathophysiological feature of chronic mental illnesses, including schizophrenia. An increase in pro-inflammatory cytokines has been described both in experimental models and in schizophrenia patients. However, not much is known about the effects that antipsychotic drugs have on intra- and intercellular mechanisms controlling inflammation. The aim of the present study was to investigate the possible anti-inflammatory effect of a standard schizophrenia treatment not only at the level of soluble mediators, but also at intra- and intercellular inflammatory pathways. The present study was conducted in a model of mild neuroinflammation using a lipopolysaccharide (LPS) challenge that was not an endotoxaemic dose (0.5 mg/kg i.p.) in young adult rats. Main results: single doses of risperidone (0.3–3.0 mg/kg i.p.) prevented increased inflammatory parameters induced by LPS in brain cortex [expression of inflammatory cytokines, interleukin (IL)-1β and tumour necrosis factor (TNF)-α, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor κB] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor γ). This is the first study demonstrating that risperidone elicits a preventive effect on the anti-inflammatory arm of the homeostatic mechanism controlling inflammation in a model of mild encephalitis in rats. Our findings suggest a possible protective effect of risperidone on brain cells.Item Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis: Toward an Integrative Inflammatory Hypothesis of Schizophrenia(Schizophrenia Bulletin, 2014) García Bueno, Borja; Mac-Dowell Mata, Karina Soledad; Rodríguez Jiménez, Roberto; Rubio Valladolid, Gabriel; Leza Cerro, Juan CarlosBackground: Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention. Methods: Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011. Results: Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors. Discussion: Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.Item Neuroplasticity and inflammatory alterations in the nucleus accumbens are corrected after risperidone treatment in a schizophrenia-related developmental model in rats(Schizophrenia Research, 2021) Tendilla Beltrán, Hiram; Coatl Cuaya, Heriberto; Meneses Prado, Silvia; Vázquez Roque, Ruben Antonio; Brambila, Eduardo; Tapia Rodríguez, Miguel; Martín Hernández, David; Garcés Ramírez, Linda; Muñoz Madrigal, José Luis; Leza Cerro, Juan Carlos; Flores, GonzaloIncreased dopaminergic activity in the striatum underlies the neurobiology of psychotic symptoms in schizophrenia (SZ). Beyond the impaired connectivity among the limbic system, the excess of dopamine could lead to inflammation and oxidative/nitrosative stress. It has been suggested that atypical antipsychotic drugs attenuate psychosis not only due to their modulatory activity on the dopaminergic/serotonergic neurotransmission but also due to their anti-inflammatory/antioxidant effects. In such a manner, we assessed the effects of the atypical antipsychotic risperidone (RISP) on the structural neuroplasticity and biochemistry of the striatum in adult rats with neonatal ventral hippocampus lesion (NVHL), which is a developmental SZ-related model. RISP administration (0.25 mg/kg, i.p.) ameliorated the neuronal atrophy and the impairments in the morphology of the dendritic spines in the spiny projection neurons (SPNs) of the ventral striatum (nucleus accumbens: NAcc) in the NVHL rats. Also, RISP treatment normalized the pro-inflammatory pathways and induced the antioxidant activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in this model. Our results point to the neurotrophic, antiinflammatory, and antioxidant effects of RISP, together with its canonical antipsychotic mechanism, to enhance striatum function in animals with NVHL.Item The interplay between functioning problems and symptoms in first episode of psychosis: An approach from network analysis(Journal of Psychiatric Research, 2021) Izquierdo, Ana; Cabello, María ; Leal, Itziar ; Mellor-Marsá, Blanca ; Ayora, Miriam ; Bravo Ortiz, María Fe; Ibáñez, Ángela ; Mac-Dowell Mata, Karina Soledad; Malpica, Norberto ; Baca García, Enrique ; Fares Otero, Natalia E. ; Melero, Helena ; López García, Pilar ; Díaz Caneja, Covadonga M. ; Ayuso Mateos, Jose Luis ; Durán Cutilla, Manuel ; Merchán Naranjo, Jessica ; Mediavilla Torres, Roberto ; Muñoz Sanjosé, Ainoa ; Sanchez Pastor, Luis ; Dompablo, Monica ; Fernández Martín, Patricia ; Puras Rico, Pablo ; Albarracin García, Lucía ; Melero Carrasco, Helena; Rodríguez Jiménez, Roberto; Díaz Marsa, Marina Francisca; Arango López, Celso; García-Albea Martín, Julia Isabel; Leza Cerro, Juan Carlos; León Quismondo, LeticiaThe relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population.Item Decreased oxytocin plasma levels and oxytocin receptor expression in borderline personality disorder(Acta Psychiatrica Scandinavica, 2020) Buenache, E.; De la Vega, I.; López‐Villatoro, J. M.; Moreno Moreno, Beatriz; Carrasco Perera, José Luis; Mac-Dowell Mata, Karina Soledad; Díaz Marsa, Marina Francisca; Leza Cerro, Juan CarlosIntroduction: Borderline personality disorder (BPD) is characterized by intense affective reactions with underlying social and interpersonal cognitive deficits. Oxytocin has largely been associated with both stress regulation and social cognition in psychiatric patients and in non-clinical populations in previous studies. Finally, abnormal oxytocin levels have been preliminary reported in BPD patients. Methods: 53 patients with moderate-severe BPD and 31 healthy control subjects were investigated for plasma levels of oxytocin and protein expression of oxytocin receptor in blood mononuclear cells. Clinical assessments were made for severity, functionality, and comorbidity with axis I and II conditions. Results: Oxytocin plasma levels were significantly lower in BPD patients compared with controls. In addition, protein expression of oxytocin receptor was significantly reduced in the BPD group. A positive correlation was found between plasma oxytocin levels and the activity index score of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Oxytocin receptor protein expression, on the contrary, had a negative correlation with the ZKPQ sociability index score. Conclusions: Results support the evidence of a dysfunction of the oxytocin system in borderline personality disorder, which could be involved in emotional dysregulation and interpersonal disturbances in these patients.Item Noradrenaline in Alzheimer's Disease: A New Potential Therapeutic Target(2022) Muñoz Madrigal, José Luis; López Gutiérrez, Irene; Dello Russo, Cinzia; Novellino, Fabiana; Caso Fernández, Javier Rubén; García Bueno, Borja; Leza Cerro, Juan CarlosA growing body of evidence demonstrates the important role of the noradrenergic system in the pathogenesis of many neurodegenerative processes, especially Alzheimer’s disease, due to its ability to control glial activation and chemokine production resulting in anti-inflammatory and neuroprotective effects. Noradrenaline involvement in this disease was first proposed after finding deficits of noradrenergic neurons in the locus coeruleus from Alzheimer’s disease patients. Based on this, it has been hypothesized that the early loss of noradrenergic projections and the subsequent reduction of noradrenaline brain levels contribute to cognitive dysfunctions and the progression of neurodegeneration. Several studies have focused on analyzing the role of noradrenaline in the development and progression of Alzheimer’s disease. In this review we summarize some of the most relevant data describing the alterations of the noradrenergic system normally occurring in Alzheimer’s disease as well as experimental studies in which noradrenaline concentration was modified in order to further analyze how these alterations affect the behavior and viability of different nervous cells. The combination of the different studies here presented suggests that the maintenance of adequate noradrenaline levels in the central nervous system constitutes a key factor of the endogenous defense systems that help prevent or delay the development of Alzheimer’s disease. For this reason, the use of noradrenaline modulating drugs is proposed as an interesting alternative therapeutic option for Alzheimer’s disease.Item Endogenous cannabinoid system regulates intestinal barrier function in vivo through cannabinoid type 1 receptor activation(American Journal of Physiology Gastrointestinal and Liver Physiology, 2012) Zoppi, Silvia; Muñoz Madrigal, José Luis; Pérez Nievas, Beatriz G.; Marín Jiménez, Ignacio; Caso Fernández, Javier Rubén; Alou Cervera, Luis; García Bueno, Borja; Colón Rodríguez, Arturo Luis; Manzanares, Jorge; Gómez-Lus Centelles, María Luisa; Menchén Viso, Luis Alberto; Leza Cerro, Juan CarlosAbstract The deleterious effects of stress on the gastrointestinal tract seem to be mainly mediated by the induction of intestinal barrier dysfunction and subsequent subtle mucosal inflammation. Cannabinoid 1 receptor (CB1R) is expressed in the mammalian gut under physiological circumstances. The aim of this investigation is to study the possible role of CB1R in the maintenance of mucosal homeostasis after stress exposure. CB1R knockout mice (CB1R−/−) and their wild-type (WT) counterparts were exposed to immobilization and acoustic (IA) stress for 2 h per day during 4 consecutive days. Colonic protein expression of the inducible forms of the nitric oxide synthase and cyclooxygenase (NOS2 and COX2), IgA production, permeability to 51Cr-EDTA, and bacterial translocation to mesenteric lymph nodes were evaluated. Stress exposure induced greater expression of proinflammatory enzymes NOS2 and COX2 in colonic mucosa of CB1R−/− mice when compared with WT animals. These changes were related with a greater degree of colonic barrier dysfunction in CB1R−/− animals determined by 1) a significantly lower IgA secretion, 2) higher paracellular permeability to 51Cr-EDTA, and 3) higher bacterial translocation, both under basal conditions and after IA stress exposure. Pharmacological antagonism with rimonabant reproduced stress-induced increase of proinflammatory enzymes in the colon described in CB1R−/− mice. In conclusion, CB1R exerts a protective role in the colon in vivo through the regulation of intestinal secretion of IgA and paracellular permeability. Pharmacological modulation of cannabinoid system within the gastrointestinal tract might be therapeutically useful in conditions on which intestinal inflammation and barrier dysfunction takes place after exposure to stress. besides its essential digestive function, the gastrointestinal tract represents the main interplay between the host and the environment, exerting an effective but also selective barrier function between the gastrointestinal mucosal immune system and the virtually infinite microbial and alimentary antigens on the mucosal surface. Intestinal epithelial cells constitute the main element of this barrier and exert pivotal roles both in the generation of tolerance toward alimentary antigens and commensal microbiota, and in the activation and orchestration of effective innate and adaptive immune responses (7, 16, 46, 47). However, intestinal barrier is a dynamic structure constituted not only by cellular components but also by an array of noncellular elements such as mucin, antimicrobial peptides, secretory immunoglobulin A (IgA) as well as apical tight junctions between adjacent epithelial cells. Tight junctions are dynamic molecular structures that constitute the rate-limiting seal of the intestinal epithelial barrier paracellular pathway (30). A huge number of proteins take part in the structure of the tight junctions, including zonula occludens (ZO) family proteins, occludin, and the numerous proteins of the claudin family (53); furthermore, the junctional complex is closely related to a ring of actin microfilaments, contraction of which seems to directly regulate paracellular permeability. Inflammatory cytokines such as interferon-γ and tumor necrosis factor-α are capable of regulating tight junction barrier function (31). Intestinal barrier dysfunction leads to the translocation to the lamina propria, lymphatic vessels and portal circulation of luminal bacteria capable of triggering and perpetuating local, and even systemic inflammation. It occurs, for example, in acute pancreatitis and advanced liver cirrhosis; moreover, an adequate transcellular absorption process depends on the presence of an intact tight junction barrier to maintain transepithelial concentration gradients. Indeed, increased intestinal permeability directly related to tight junction dysfunction is a characteristic feature of ulcerative colitis, Crohn's disease, celiac disease, and food allergies (2, 12). Also, intestinal tight junction disruption has been shown in experimental models of stress, assuming their direct responsibility on the increased intestinal permeability that characterizes acute stress in laboratory animals (11, 33, 37). In this sense, exposure to physical and psychological stress triggers and/or modifies the clinical course of a variety of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) (6, 49). Growing evidence from experimental studies supports the ability of psychosocial stress to induce biochemical and histological inflammatory changes in the intestinal mucosa. Indeed, animal stress models represent an excellent tool to assess intestinal barrier physiology and pathophysiology. A common finding observed in several models of stress-induced intestinal inflammation is an increased expression and activity of the inducible isoforms of nitric oxide synthase (NOS2) and cyclooxygenase (COX2) in intestinal tissue homogenates (9). The resulting high concentrations of NO and other reactive oxygen and nitrogen species produced by NOS2 as well as COX2-derived prostaglandin E2 have been involved in barrier dysfunction (3) and water/chloride secretion (48), respectively, associated with intestinal inflammatory conditions. A wide variety of results suggest that such intestinal inflammatory response triggered by psychological and physical stress could be mediated, at least in part, by the induction of intestinal barrier dysfunction resulting in bacterial translocation and enhanced uptake of luminal antigens (9). The endogenous cannabinoid system regulates many different functions in the gastrointestinal system of vertebrates. The two types of cannabinoid receptors (CBR) that have been discovered and cloned, CB1R and CB2R (20), are differentially expressed in the human colon; whereas CB1R is expressed in intestinal epithelial cells, smooth muscle, myenteric plexus, and lamina propria plasma cells, CB2R is mainly expressed under physiological circumstances in plasma cells and macrophages (51) but has also been recently found in myenteric and submucosal neurons of rodent (13) and human bowel samples (52). The effects of CBR activation and the physiological roles for endocannabinoids in the gastrointestinal tract have been extensively reviewed (23); briefly, CB1R activation acts mostly via brain-gut axis to reduce gastrointestinal motility, diarrhea, pain or hyperalgesia, transient lower esophageal sphincter relaxations, emesis, and gastric acid secretion, as well as to promote eating; CB2R activation acts mostly via immune cells to reduce inflammation (39) through, at least, an inhibitory effect on interleukin-8 release in human colonic epithelial cells (21). A role for gastrointestinal carcinogenesis has also been suggested, as downregulation of CB1R and upregulation of CB2R have been observed in intestinal samples of patients with colon cancer (22). However, the role of the endocannabinoid system, and in particular CB1R, in intestinal barrier function and mucosal homeostasis is still largely unknown; however, although the exact mechanisms are poorly understood, some findings support the notion of an endogenous anti-inflammatory activity of CB1R because mice lacking CB1R show enhanced colitis compared with their wild-type (WT) littermates (32, 42). Consistent with this observation, administration of CBR agonists (26) or targeting endocannabinoid degradation (43) has been shown to protect against various forms of experimental colitis in animal models. Nevertheless, the role of the endocannabinoid system in intestinal barrier function has not been previously explored. Therefore, in the present study, we aim to investigate whether CB1R modulates intestinal barrier function in mice exposed to immobilization and acoustic (IA) stress; for this purpose we took advantage of the use of genetically modified mice lacking CB1R as well as pharmacological manipulation of CB1R. We report herein that stress-induced changes were related with a greater colonic barrier permeability and inflammation, lower IgA secretion, and higher bacterial translocation when CB1R is absent.- Project number: 273
Item Elaboración de casos clínicos para el aprendizaje basado en casos prácticos: una herramienta pedagógica para la inmersión en la materia de profesores noveles y un recurso didáctico en la metodología de aprendizaje con participación del estudiante(2023) Gutiérrez López, María Dolores; Caballero Collado, Ricardo; Caso Fernández, Javier Rubén; Delpón Mosquera, María Eva; García Bueno, Borja; Leza Cerro, Juan Carlos; Lizasoaín Hernández, Ignacio; McDowell Mata, Karina; Morales Cano, Daniel; Moreno Gutiérrez, Laura; Muñoz Madrigal, José Luis; O'Shea Gaya, María Esther; Pérez Vizcaíno, Francisco; Tejerina Sánchez, María Teresa; Vidal Casado, Rebeca; Vidal Marcos, Alfonso; Martín Hernández, David; Malan-Müller, Stefanie; Olivencia Plaza, Miguel Ángel; Morales Puerto, Nuria; Núñez de la Calle, Carlos; Vicente Crespo, Maria Elena; Cogolludo Torralba, Ángel LuisEl proyecto propone la elaboración de nuevos casos clínicos que asemejen situaciones reales sobre los que los estudiantes puedan desarrollar un aprendizaje autónomo dirigido por el profesorado en función de los conceptos que sean de interés para cada grupo farmacológico y acercándole a la situación más cercana a su práctica profesional. Los objetivos del proyecto son: 1) Generar una base de nuevos casos clínicos dirigidos a que los estudiantes trabajen sobre grupos de fármacos en un contexto lo más real posible. Los diferentes casos que se elaboren en este proyecto podrán ser utilizados en la docencia de diversas asignaturas impartidas por miembros del departamento de Farmacología y Toxicología. Las sesiones dirigidas al estudio basado en la resolución de casos se plantean como una herramienta docente que tiene como finalidad el desarrollo de competencias transversales como promover la motivación, el trabajo en equipo, la participación de los estudiantes en los debates, así como, fomentar el pensamiento crítico y el conocimiento del método científico. Este tipo de aprendizaje en contexto facilita la integración de los conocimientos y su mayor retención además de la dotar a los estudiantes con las habilidades para fomentar un aprendizaje continuo. 2) Apoyar la formación del profesorado de reciente incorporación, así como del personal investigador que participan como colabores en tareas docentes del departamento y que podrían ser potenciales futuros docentes. Item Paliperidone reverts Toll-like receptor 3 signaling pathway activation and cognitive deficits in a maternal immune activation mouse model of schizophrenia(Neuropharmacology, 2017) Mac-Dowell Mata, Karina Soledad; Munarriz Cuezva, Eva; Caso Fernández, Javier Rubén; Muñoz Madrigal, José Luis; Zabala, Arantzazu; Meana, J. Javier; García Bueno, Borja; Leza Cerro, Juan CarlosThe pathophysiology of psychotic disorders is multifactorial, including alterations in the immune system caused by exogenous or endogenous factors. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop schizophrenia (SZ) along lifetime. Here, we tested the hypothesis that the antipsychotic paliperidone regulates immune-related brain effects in an experimental model of SZ. A well described prenatal immune activation model of SZ in mice by maternal injection of the viral mimetic poly(I:C) during pregnancy was used. Young-adult offspring animals (60PND) received paliperidone ip (0.05 mg/kg) for 21 consecutive days. One day after last injection, animals were submitted to a cognitive test and brain frontal cortex (FC) samples were obtained for biochemical determinations. The adults showed an activated innate immune receptor TLR-3 signaling pathway, oxidative/nitrosative stress and accumulation of pro-inflammatory mediators such as nuclear transcription factors (i.e., NFκB) and inducible enzymes (i.e., iNOS) in FC. Chronic paliperidone blocked this neuroinflammatory response possibly by the synergic activation and preservation of endogenous antioxidant/anti-inflammatory mechanisms such as NRF2 and PPARγ pathways, respectively. Paliperidone administration also stimulated the alternative polarization of microglia to the M2 anti-inflammatory profile. In addition, paliperidone treatment improved spatial working memory deficits of this SZ-like animal model. In conclusion, chronic administration of paliperidone to young-adult mice prenatally exposed to maternal immune (MIA) challenge elicits a general preventive anti-inflammatory/antioxidant effect at both intracellular and cellular polarization (M1/M2) level in FC, as well as ameliorates specific cognitive deficits.Item Paliperidone Prevents Brain Toll-Like Receptor 4 Pathway Activation and Neuroinflammation in Rat Models of Acute and Chronic Restraint Stress(International Journal of Neuropsychopharmacology, 2015) Mac-Dowell Mata, Karina Soledad; Caso Fernández, Javier Rubén; Martín Hernández, D.; Muñoz Madrigal, José Luis; Leza Cerro, Juan Carlos; García Bueno, BorjaBackground: Alterations in the innate immune/inflammatory system have been proposed to underlie the pathophysiology of psychotic disease, but the mechanisms implicated remain elusive. The main agents of the innate immunity are the family of toll-like receptors (TLRs), which detect circulating pathogen-associated molecular patterns and endogenous damage-associated molecular patterns (DAMPS). Current antipsychotics are able to modulate pro- and anti-inflammatory pathways, but their actions on TLRs remain unexplored. Methods: This study was conducted to elucidate the effects of paliperidone (1mg/Kg i.p.) on acute (6 hours) and chronic (6 hours/day during 21 consecutive days) restraint stress-induced TLR-4 pathway activation and neuroinflammation, and the possible mechanism(s) related (bacterial translocation and/or DAMPs activation). The expression of the elements of a TLR-4-dependent proinflammatory pathway was analyzed at the mRNA and protein levels in prefrontal cortex samples. Results: Paliperidone pre-treatment prevented TLR-4 activation and neuroinflammation in the prefrontal cortices of stressed rats. Regarding the possible mechanisms implicated, paliperidone regulated stress-induced increased intestinal inflammation and plasma lipopolysaccharide levels. In addition, paliperidone also prevented the activation of the endogenous activators of TLR-4 HSP70 and HGMB-1. Conclusions: Our results showed a regulatory role of paliperidone on brain TLR-4, which could explain the therapeutic benefits of its use for the treatment of psychotic diseases beyond its effects on dopamine and serotonin neurotransmission. The study of the mechanisms implicated suggests that gut-increased permeability, inflammation, and bacterial translocation of Gram-negative microflora and HSP70 and HGMB1 expression could be potential adjuvant therapeutic targets for the treatment of psychotic and other stress-related psychiatric pathologies.