Glia mechanisms in mood regulation: a novel model of mood disorders |
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Authors: | Younglim Lee Denise Gaskins Amit Anand Anantha Shekhar |
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Institution: | (1) Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA;(2) Institute of Psychiatric Research, Indiana University Medical Center, 791 Union Drive, Indianapolis, IN 46202, USA |
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Abstract: | Introduction Recent evidence in clinical and preclinical studies has implicated glutamate neurotransmissions in pathophysiology of mood
disorders. The regulation of amino acid neurotransmission, i.e., glutamate and gamma-aminobutyric acid (GABA) involves coordinated
mechanisms of uptake and transport within a tripartite synaptic system that includes neurons and glia. Newly appreciated role
of the glia, more specifically astrocytes on neuronal functions combined with reported postmortem abnormalities of glia in
patients with mood disorders further supports the role of glia in mood disorders.
Materials and methods This report presents some of our preliminary results utilizing glia-selective toxins and other pharmacological tools to suppress
glial function within the limbic system to study the resulting behavioral abnormalities, and thus, elucidate glial involvement
in the development of mood disorders.
Results and discussion We demonstrate that chronic blockade of glutamate uptake by a glial/neuronal transporter antagonist l-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) within the amygdala, a key area implicated in mood regulation, results in dose-dependent
reduction in social exploratory behavior and disrupts circadian activity patterns consistent with symptoms of mood disorders.
Similarly, the selective astrocytic glutamate transporter type 1 (GLT-1) blocker dihydrokainic acid (DHK) injected into the
amygdala also results in reduced social interaction that is blocked by selective glutamate N-methyl-d-aspartate (NMDA) type receptor antagonist AP5. The results are discussed in the context of glial and glutamate mechanisms
in mood disorders and potential therapeutic avenues to address these mechanisms. |
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Keywords: | Astrocytes Depression NMDA Amygdala Circadian rhythm |
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