Inhibition of Excitatory Amino Acid-Induced Neurotoxicity by a Tau Antisense Oligonucleotide in Primary Culture of Cerebellar Granule Cells

Abstract

Excitatory amino acid neurotransmission in the mammalian central nervous system is mediated principally by glutamate and structurally related compounds. It is estimated that glutamate is the primary neurotransmitter in approximately 50% of the synapses in the mammalian forebrain. In fact, nearly all neurons can be excited by glutamate. In addition to its involvement in information coding, glutamate may also act as neurotrophic factor by participating in the cytoarchitectural organization of neurons during brain development (McDonald and Johnston, 1990). These effects can be also detected in vitro. When tested on primary culture of different types of neuronal cells during differentiation, glutamate through the stimulation of specific glutamate receptor subtypes induces the major stages of development, such as neurite extension and branching, and synaptogenesis (Balais et al., 1989). In particular, the ability of glutamate to influence the structure of developing neurons and their pattern of interconnectivity is likely related to its capacity to alter cytosolic calcium levels through stimulation of a specific subtype of ionotropic glutamate receptors, namely the N-Methyl-D-Aspartate (NMDA)-selective glutamate receptor.KeywordsCerebellar Granule CellPaired Helical FilamentSubacute Sclerosing PanencephalitisPaired Helical FilamentExcitatory Amino Acid NeurotransmissionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.