Background: Basic fibroblast growth factor (FGF2) plays a crucial role during the development of the cerebral cortex. Mice with a knockout of the FGF2 gene have a reduced number of glutamatergic neurons within the deep layers of the cerebral cortex. Methods: We used molecular and behavioral analyses to investigate possible alterations in corticostriatal function in FGF2 / mice. Results: We found that FGF2 deficiency leads to decreased expression of presynaptic markers of integrity for glutamatergic fibers in the striatum, namely the membrane excitatory amino acid transporter 3 (EAAT3) and the vesicular glutamate transporter 1 (VGLUT1). The reduction of corticostriatal glutamatergic function in FGF2/mice is associated with enhanced locomotor activity in a novel environment and increased responsiveness to dopaminergic drugs, such as cocaine or amphetamine. The behavioral alterations of FGF2 / can be normalized by injection of a low dose of the dopaminergic agonist apomorphine (.1 mg/kg) that reduces dopamine release by acting on presynaptic receptors. Conclusions: Our data demonstrate that FGF2 / mice have an increased tone and responsiveness of the dopaminergic system and suggest that these animals might represent a model to study disorders that are characterized by an imbalance between glutamatergic and dopaminergic neurotransmission.

Reduction of Corticostriatal Glutamatergic Fibers in Basic Fibroblast Growth Factor Deficient Mice is Associated with Hyperactivity and Enhanced Dopaminergic Transmission

FADDA, PAOLA;COLLU, MARIA;
2007

Abstract

Background: Basic fibroblast growth factor (FGF2) plays a crucial role during the development of the cerebral cortex. Mice with a knockout of the FGF2 gene have a reduced number of glutamatergic neurons within the deep layers of the cerebral cortex. Methods: We used molecular and behavioral analyses to investigate possible alterations in corticostriatal function in FGF2 / mice. Results: We found that FGF2 deficiency leads to decreased expression of presynaptic markers of integrity for glutamatergic fibers in the striatum, namely the membrane excitatory amino acid transporter 3 (EAAT3) and the vesicular glutamate transporter 1 (VGLUT1). The reduction of corticostriatal glutamatergic function in FGF2/mice is associated with enhanced locomotor activity in a novel environment and increased responsiveness to dopaminergic drugs, such as cocaine or amphetamine. The behavioral alterations of FGF2 / can be normalized by injection of a low dose of the dopaminergic agonist apomorphine (.1 mg/kg) that reduces dopamine release by acting on presynaptic receptors. Conclusions: Our data demonstrate that FGF2 / mice have an increased tone and responsiveness of the dopaminergic system and suggest that these animals might represent a model to study disorders that are characterized by an imbalance between glutamatergic and dopaminergic neurotransmission.
fibroblast growth factor; schizophrenia; animal model
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/19944
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