Orio Ortiz, Laura

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Orio Ortiz
Universidad Complutense de Madrid
Faculty / Institute
Psicobiología y Metodología en Ciencias del Comportamiento
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Now showing 1 - 9 of 9
  • Publication
    Reelin plasma levels identify cognitive decline in alcohol use disorder patients during early abstinence: the influence of APOE4 expression
    (Oxford Academic, 2023-06-23) Escudero Moreno, Berta; Moya Montes, Marta; López Valencia, Leticia; Arias Horcajadas, Francisco; Orio Ortiz, Laura
    Background: Apolipoprotein E (APOE)-4 isoform, reelin, and clusterin share very–low-density liporeceptor and apolipoprotein E receptor 2 receptors and are related to cognition in neuropsychiatric disorders. These proteins are expressed in plasma and brain, but studies involving plasma expression and cognition are scarce. Methods: We studied the peripheral expression (plasma and peripheral blood mononuclear cells) of these proteins in 24 middle-aged patients with alcohol use disorder (AUD) diagnosed at 4 to 12 weeks of abstinence (t = 0) and 34 controls. Cognition was assessed using the Test of Detection of Cognitive Impairment in Alcoholism. In a follow-up study (t = 1), we measured reelin levels and evaluated cognitive improvement at 6 months of abstinence. Results: APOE4 isoform was present in 37.5% and 58.8% of patients and controls, respectively, reaching similar plasma levels in ε4 carriers regardless of whether they were patients with AUD or controls. Plasma reelin and clusterin were higher in the AUD group, and reelin levels peaked in patients expressing APOE4 (P < .05, η2 = 0.09), who showed reduced very–low-density liporeceptor and apolipoprotein E receptor 2 expression in peripheral blood mononuclear cells. APOE4 had a negative effect on memory/learning mainly in the AUD group (P < .01, η2 = 0.15). Multivariate logistic regression analyses identified plasma reelin as a good indicator of AUD cognitive impairment at t = 0. At t = 1, patients with AUD showed lower reelin levels vs controls along with some cognitive improvement. Conclusions: Reelin plasma levels are elevated during early abstinence in patients with AUD who express the APOE4 isoform, identifying cognitive deterioration to a great extent, and it may participate as a homeostatic signal for cognitive recovery in the long term.
  • Publication
    Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for “Diabesity”
    (ACS, 2022) Decara, Juan M.; Vázquez Villa, Henar; Brea, José; Alonso, Mónica; Srivastava, Raj Kamal; Orio Ortiz, Laura; Alen Fariñas, Francisco; Suárez, Juan; Baixeras, Elena; García Cárceles, Javier; Escobar Peña, Andrea; Lutz, Beat; Rodríguez, Ramón; Codesido, Eva; Garcia Ladona, F. Javier; Bennett, Teresa A.; Ballesteros, Juan A.; Cruces, Jacobo; Loza, María I.; Benhamú Salama, Bellinda; Rodríguez de Fonseca, Fernando; López Rodríguez, María L.
    Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small molecules acting as positive allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4- {[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)- piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-molecule PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.
  • Publication
    Revista científica Complutense Psicología de las Adicciones 2015 (volumen 3): Una herramienta docente innovadora para mejorar el sistema de enseñanza-aprendizaje de grado y posgrado en psicología y psicofarmacología de las adicciones.
    (2016-01-30) García Fernández, Gloria; Gómez de las Heras, Raquel; Orio Ortiz, Laura; Sánchez Ruiz de León, José María; Molina, José Antonio; Rodríguez, Fernando
  • Publication
    Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice
    (2019) Alén Fariñas, Francisco; Gómez-Redondo, Isabel; Rivera, Patricia; Suárez, Juan; Ramos-Ibeas, Priscila; Pericuesta, Eva; Fernández-González, Raul; Perez-Cerezales, Serafín; Horiuchi, Keiko; Orio Ortiz, Laura; Rodriguez de Fonseca, Fernando; Gutiérrez-Adán, Alfonso
    Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.
  • Publication
    Short mindfulness meditation training: does it really reduce perceived stress?
    (Springer Nature, 2022-09-21) Horrillo Álvarez, Barbara; Marín Martín, Carolina; Rodríguez Abuín, Manuel; Orio Ortiz, Laura
    To study whether an 8-week mindfulness meditation training program truly reduces perceived stress without designing a stress reduction program. An experimental study was performed in which we studied the efects of 8 weeks of MM training on attention and awareness, as measured by the MAAS (mindfulness attention awareness scale) and perceived stress, as measured by the PSQ (perceived stress questionnaire), in 80 volunteers from the general public recruited by email from university centers. An increase in the individual’s dispositional capacity to be attentive and aware of the experience of the present moment in everyday life was observed in the experimental group versus the control group; F (2, 156)=14.30, p=.000, η2 partial=.155. Perceived stress showed no signifcant diferences between groups in: social acceptance; F (2, 156)=2.30, p=.103, overload; F (2, 156)=2.32, p=.101, irritability, tension and fatigue; F (2, 156)=2.27, p=.106, energy and joy; F (2, 156)=2.79, p=.065. MM practice for 8 weeks of training increases the individual’s dispositional capacity to be attentive and aware of the experience of the present moment in everyday life but may not reduce perceived stress.
  • Publication
    Cerebellar and cortical TLR4 activation and behavioral impairments in Wernicke-Korsakoff Syndrome: Pharmacological effects of oleoylethanolamide
    (Elsevier, 2020-12-01) Moya Montes, Marta; San Felipe Riba, Diego; Ballesta, Javier Antonio; Alen Fariñas, Francisco; Rodríguez de Fonseca, Fernando; García Bueno, Borja; Marco López, Eva María; Orio Ortiz, Laura
    Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric disorder whose etiology is a thiamine deficiency (TD), with alcoholism being the main underlying cause. Previous evidence suggests the presence of initial neuroinflammation and oxidative/nitrosative stress in the physiopathology, although the specific molecular mechanisms underlying TD-induced brain damage and behavioral disabilities are unknown. We explored the specific role of the innate immune receptor TLR4 in three murine models of WKS, based on the combination of a thiamine-deficient diet and pyrithiamine injections (0.25 mg/kg, i.p.) over time. The Symptomatic Model (SM) allowed us to describe the complete neurological/neurobehavioral symptomatology over 16 days of TD. Animals showed an upregulation of the TLR4 signaling pathway both in the frontal cortex (FC) and cerebellum and clear motor impairments related with cerebellar dysfunction. However, in the Pre-Symptomatic Model (PSM), 12 days of TD induced the TLR4 pathway upregulation in the FC, which correlated with disinhibited-like behavior, but not in the cerebellum, and no motor impairments. In addition, we tested the effects of the biolipid oleoylethanolamide (OEA, 10 mg/kg, i.p., once daily, starting before any symptom of the pathology is manifested) through the Glucose-Precipitated Model (GPM), which was generated by glucose loading (5 g/kg, i.v., last day) in thiamine-deficient animals to accelerate damage. Pretreatment with OEA prevented the TLR4-induced signature in the FC, as well as an underlying incipient memory disability and disinhibited-like behavior. This study suggests a key role for TLR4 in TD-induced neuroinflammation in the FC and cerebellum, and it reveals different vulnerability of these brain regions in WKS over time. Pre-treatment with OEA counteracts TD-induced TLR4-associated neuroinflammation and may serve as co-adjuvant therapy to prevent WKS-induced neurobehavioral alterations.
  • Publication
    Antianhedonic and Antidepressant Effects of Affron®, a Standardized Saffron (Crocus Sativus L.) Extract
    (MDPI, 2020-07-15) Orio Ortiz, Laura; Alen Fariñas, Francisco; Ballesta García, Antonio; Martín Martín, Raquel; Gómez de Heras, Raquel
    Anxiety and depression have high prevalence in the general population, affecting millions of people worldwide, but there is still a need for effective and safe treatments. Nutritional supplements have recently received a lot of attention, particularly saffron. Thus, several pre-clinical studies support a beneficial role for bioactive compounds, such as saffron, in anxiety and depression. Here we used an animal model of depression based on social isolation to assess the effects of affron®, a standardized saffron extract containing ≥3.5% of total bioactive compounds safranal and crocin isomers. Affron® was administered both through the oral and the intraperitoneal routes, and several tasks related to anxiety and depression, such as the elevated plus maze, the forced swimming test or the sucrose preference test, were assessed. These tasks model key features of depressive states and anxious states relating to fear, behavioral despair or anhedonia, the lack of motivation and/or pleasure from everyday activities, respectively. Animals receiving oral affron® displayed behaviors congruent with improvements in their anxious/depressive state, showing the enhanced consumption of a sweet solution, as well as an increase in certain escape responses in the forced swimming test. Our data support a beneficial role for oral saffron in anxious/depressive states.
  • Publication
    Programas de Auxiliares Docentes Postgraduados
    (2020-11-05) Pérez García, Eva María; Bolaños Cartujo, José Ignacio; Barrón López De Roda, Ana; Casado Martínez, María del Pilar; Iglesias Soilán, Manuel; Martín Dobón, Elisa; Enguídanos Vanderweyen, Daniel; Escorial Martín, Sergio; Fernández González, Santiago; Gómez Ruiz, María Sagrario; Ondé Pérez, Daniel; Orio Ortiz, Laura; Rio Grande, David Pedro del
  • Publication
    Revista científica simulada Psicología de la Adicción UCM 2014 (Volumen 2)
    (2015-02-13) García-Fernández, Gloria; Gómez de Heras, María Raquel; Jurado Barba, Rosa; Orio Ortiz, Laura; Ruíz Sanches de León, José Maria