title: Exposure to the cytokine EGF leads to abnormal hyperactivity of pallidal GABA neurons: implications for schizophrenia and its modeling.
abstract: Previous studies on a cytokine model for schizophrenia reveal that the hyperdopaminergic innervation and neurotransmission in the globus pallidus (GP) is involved in its behavioral impairments. Here, we further explored the physiological consequences of the GP abnormality in the indirect pathway, using the same schizophrenia model established by perinatal exposure to epidermal growth factor (EGF). Single-unit recordings revealed that the neural activity from the lateral GP was elevated in EGF-treated rats in vivo and in vitro (i.e., slice preparations), whereas the central area of the GP exhibited no significant differences. The increase in the pallidal activity was normalized by subchronic treatment with risperidone, which is known to ameliorate their behavioral deficits. We also monitored extracellular GABA concentrations in the substantia nigra, one of the targets of pallidal efferents. There was a significant increase in basal GABA levels in EGF-treated rats, whereas high potassium-evoked GABA effluxes and glutamate levels were not affected. A neurotoxic lesion in the GP of EGF-treated rats normalized GABA concentrations to control levels. Corroborating our in vivo results, GABA release from GP slices was elevated in EGF-treated animals. These findings suggest that the hyperactivity and enhanced GABA release of GP neurons represent the key pathophysiological features of this cytokine-exposure model for schizophrenia.
authors: Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors: Hidekazu
authors: H
authors: Sotoyama
authors: Hisaaki
authors: H
authors: Namba
authors: Satomi
authors: S
authors: Chiken
authors: Atsushi
authors: A
authors: Nambu
authors: Hiroyuki
authors: H
authors: Nawa
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology; D012559:Schizophrenia / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D005680:gamma-Aminobutyric Acid; D004815:Epidermal Growth Factor; D018967:Risperidone
keywords: GABA; cytokine; epidermal growth factor; globus pallidus; indirect pathway; neurotrophic factor; schizophrenia