Blocking neurotransmitter receptors, inducing CNS injury | 48861

Journal of Neuroscience and Neuropharmacology

Blocking neurotransmitter receptors, inducing CNS injury

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Ane Murueta-Goyena Larranaga

University of the Basque Country, Spain

Posters & Accepted Abstracts: Neurochem Neuropharm

Abstract :

The function of N-methyl-D-aspartate receptor (NMDAr) is critical for the processes underlying learning, memory and synaptic plasticity. The hypofunction of NMDAr is currently the most accepted hypothesis for the pathophysiology of schizophrenia. This condition is induced in animal models using NMDA antagonist drugs, such as MK801, also known as Dizocilpine. Repeated injections during early postnatal days seem to be necessary to induce long-term structural brain changes and behaviours reminiscent of schizophrenia. Disturbances in glutamartergic transmission are especially relevant to mimic negative and cognitive symptoms of the disease. Schizophrenia is considered a neurodevelopmental disorder, although symptoms usually emerge during late adolescence/early adulthood, coinciding with GABAergic circuit maturation. It has been suggested that NMDA hypofunction preferentially affects GABAergic interneurons and perturbs the maturation of GABAergic circuits, including disrupted synaptic integration in early brain development and modified network activity and plasticity in adulthood. One of the most consistent findings is a downregulation of parvalbumin (PV) and glutamate descarboxylase 67 (GAD67) expressions in PV+ interneurons, which have been reliably reproduced in animal models of MK801. The modification in PV+ activity in prefrontal cortex and hippocampus generates a dyssynchrony in gamma oscillations, which are necessary for attention maintenance, working memory and executive functions in humans and rodents. One of the major challenges in schizophrenia research is trying to modify brain circuits that present long lasting aberrant synaptic wiring.

Biography :