Group of Molecular Neuropsychopharmacology

Department of Pharmacology and Toxicology
Faculty of Medicine

Neuroinflammatory processes occur in many psychiatric and neurological diseases. Our main goal is to generate new and useful pharmacological strategies in neuropsychiatric pathologies, as well as the search for biomarkers. We also focus on identifying and to developing pharmacological tools in order to improve the quality of treatments for patients suffering these diseases.
Our specific aims are:

– Characterization of immune/inflammatory signaling mechanisms in CNS, regulatory mechanisms and possible new pharmacological targets.
– Study of the physiopathological causes and consequences of an inadequate immune/inflammatory response in central nervous system (CNS).
– Pro/antiinflammatory mechanisms in mental health diseases and their relationship with the symptomatology presented, particularly in psychosis and affective disorders. Identification of new pharmacological targets for novel or already used drugs.
– Pro/antiinflammatory mechanisms in neurodegenerative diseases and their relationship with the symptomatology presented particularly in Alzheimer’s disease. Special role of the chemokine MCP-1.
– Immune/inflammatory pathophysiology in other neuropsychiatric diseases: eating disorders, impulsivity disorders of autism spectrum diseases.
– Role of gut and mouth bacterial translocation in the brain response to stress. Intestinal and oral microbiome and mental health.

The Department at the UCM has all the equipment needed, including: apparatus for molecular biology techniques (Western blot, ELISAs, RIAs, EIAs), dark room and Odyssey Imaging System (LI-COR) for developing molecular biology films, real time PCR (RT-PCR) apparatus, fluorescence spectrophotometers and UV-V, Luminex, Nanodrop and Microplate readers, sliding microtome and microinjection and perfusion pumps and stereotaxic apparatus for surgery in rodents, ultra- and refrigerate centrifuges, precision scales, pHmeters, autoclaves, incubators, orbital shakers, vortex, magnetic stirrers, cold room and refrigerators and freezers, tissue culture room and Milli-Q water installation, ultrasonic sonicators and Tissue-Lyser for processing samples and beta and gamma radiation counters. Moreover, the UCM has assistance centers (CAIS: Centros de Apoyo a la Investigación): Animal Facilities, the Flow Cytometry and Microscopy Facility as well as Genomic and Proteomic Units.

Affective and psychotic diseases (major depression [MD] and schizophrenia [SZ]) constitute the main psychiatric pathologies. However, current treatments are sub-optimal and fail in many patients. Furthermore, epidemiological studies indicate a relationship between systemic inflammatory conditions and mental health diseases, especially those implicated in dysbiosis in the digestive tract or oral cavity.
Objectives:

  1. To study mechanisms contributing to neuroinflammation in MD and SZ, by using experimental stress models in rodents. We will investigate the mechanisms whereby inflammatory elements enter into the brain during oral and gut dysbiosis and bacterial translocation trough natural barriers (leaky-gut/mouth). Different behavioral and biochemical parameters will be investigated as well as novel intra- and extracellular inflammatory and oxidative parameters currently underexplored in this context, such as different lipopolysaccharides (LPS), receptors and specific signaling pathways, microglial activation and polarization.
  2. To determine how dysbiotic sequelae and neuroinflammation influence neuropsychiatric disorders in human samples of MD and SZ (brain bank and DNA bank from CIBERSAM: www.cibersam.es/en).
  3. To investigate whether pharmacological modulation of parameters, previously identified, reduces neuroinflammation in the experimental models. Identification of biochemical parameters and means to modulate them could be useful as state/trait biomarkers and provide promising therapeutic targets for the management MD and SZ.

Stable collaborations: Spanish scientific network Mental health research (CIBERSAM: https://www.cibersam.es/en) and Research Institute Hospital 12 de Octubre (https://imas12.es/).