Research article summary (published 29 Jun 2009):

Serotonergic hyperinnervation and effective serotonin blockade in an FGF receptor developmental model of psychosis.

Full Abstract

The role of fibroblast growth factor receptors (FGFR) in normal brain development has been well-documented in transgenic and knock-out mouse models. Changes in FGF and its receptors have also been observed in schizophrenia and related developmental disorders. The current study examines a transgenic th(tk-)/th(tk-) mouse model with FGF receptor signaling disruption targeted to dopamine (DA) neurons, resulting in neurodevelopmental, anatomical, and biochemical alterations similar to those observed in human schizophrenia. We show in th(tk-)/th(tk-) mice that hypoplastic development of DA systems induces serotonergic hyperinnervation of midbrain DA nuclei, demonstrating the co-developmental relationship between DA and 5-HT systems. Behaviorally, th(tk-)/th(tk-) mice displayed impaired sensory gaiting and reduced social interactions correctable by atypical antipsychotics (AAPD) and a specific 5-HT2A antagonist, M100907. The adult onset of neurochemical and behavioral deficits was consistent with the postpubertal time course of psychotic symptoms in schizophrenia and related disorders. The spectrum of abnormalities observed in th(tk-)/th(tk-) mice and the ability of AAPD to correct the behavioral deficits consistent with human psychosis suggests that midbrain 5-HT2A-controlling systems are important loci of therapeutic action. These results may provide further insight into the complex multi-neurotransmitter etiology of neurodevelopmental diseases such autism, bipolar disorder, Asperger's Syndrome and schizophrenia.

Author information

Author/s: Klejbor, Ilona (I); Kucinski, Aaron (A); Wersinger, Scott R (SR); Corso, Thomas (T); Spodnik, Jan H (JH); Dziewiatkowski, Jerzy (J); Morys, Janusz (J); Hesse, Renae A (RA); Rice, Kenner C (KC); Miletich, Robert (R); Stachowiak, Ewa K (EK); Stachowiak, Michal K (MK);

Affiliation: Department of Pathology and Anatomical Sciences, SUNY, Buffalo, NY 14214, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Schizophrenia research (Schizophr Res), published in Netherlands. (Language: eng)

Reference: 2009-Sep; vol 113 (issue 2-3) : pp 308-21

Dates: Created 2009/08/11; Completed 2009/10/29;

PMID: 19570652, status: MEDLINE (last retrieval date: 10/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Animals, Newborn Antipsychotic Agents - therapeutic use Behavior, Animal Disease Models, Animal Exploratory Behavior - physiology Female Fluorobenzenes - therapeutic use Gait Disorders, Neurologic - drug therapy; genetics Grooming - physiology Hydroxyindoleacetic Acid - metabolism Male Mice

Mice Mice, Inbred C57BL Mice, Transgenic Neural Inhibition - genetics Piperidines - therapeutic use Protein-Tyrosine Kinases - genetics Psychotic Disorders - genetics; metabolism; physiopathology Rats Receptors, Fibroblast Growth Factor - genetics; metabolism Serotonin - metabolism Serotonin Antagonists - therapeutic use Social Behavior Startle Reaction - genetics

Associated Chemicals: Antipsychotic Agents (0) ; Fluorobenzenes (0) ; Piperidines (0) ; Receptors, Fibroblast Growth Factor (0) ; Serotonin Antagonists (0) ; MDL 100907 (139290-65-6) ; Serotonin (50-67-9) ; Hydroxyindoleacetic Acid (54-16-0) ; Protein-Tyrosine Kinases (EC 2.7.1.112)

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