RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development

Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later matura- tion. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine pre- cursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation. However, in later development, a novel Rac1 GAP, ARHGAP23, and RhoGDIs inactivate actomyosin dynamics to stabilize mature synap- ses. Our observations demonstrate that specific combinations of RhoGTPase regulatory pro- teins temporally balance RhoGTPase activity during post-synaptic spine development

Glial Cells in the Schizophrenia Puzzle: Angiotensin II Role

Schizophrenia is a neuropsychiatric disease with 1% worldwide prevalence and characterized by a deep distortion in thought and perception, cognitive dysfunction, and social behavioral deficits. After the discovery of the antipsychotic effects of chlorpromazine, a large body of evidence pointed out to the neurotransmission misbalance as the main factor in the development of this pathology. Nowadays, it is known that schizophrenia is related to a pluri-factorial etiopathogenesis where gene factors, neuroinflammation, and brain microenvironment?s alterations are taken into account as well. In this sense, glial cells (oligodendrocytes, astrocytes, and microglial cells) are essential pieces in brain microenvironment with crucial roles in synaptic establishment and function, neuroinflammation, and metabolic and ion homeostasis, among others. Currently, glial cells are the target of numerous researches on the race to puzzle out the schizophrenia etiopathology.Among the multiplicity of regulatory substances involved in glial cell functionality, it becomes outstanding the newly described roles for brain angiotensin II (Ang II). This neuropeptide, through its AT1 receptors (AT1-R), expressed in neurons and glial cells modulates brain homeostasis and several neurotransmission systems (dopaminergic, glutamatergic, and GABAergic) and has a pro-inflammatory role in pathological conditions. In this way, Ang II has been involved in cognition processes, stress responses, and mental disorders such as schizophrenia, addiction, Parkinson?s, and Alzheimer?s diseases.In this chapter, we aimed to summarize the role of the glial cells in the schizophrenia with a special reference to AT1-R involvement in this complex scenario.Fil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Marchese, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Rodríguez, Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Jaime, Andrea del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Herrera Lopez, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin