Antidepressant Treatments Induce the Expression of Basic Fibroblast Growth Factor in Cortical and Hippocampal Neurons

Abstract

New experimental evidence suggests that the mechanism of action of antidepressants includes the induction of neurotrophic factor synthesis in selected brain areas. The present study is aimed at establishing whether prolonged antidepressant treatments increase the expression of basic fibroblast growth factor (FGF2), a polypeptide growth factor that has a broad neurotrophic activity in the adult central nervous system. Rats received a single dose or long-term (3 weeks) administration of desipramine (DMI), fluoxetine (FLU), and mianserin (MIA), then were sacrificed at 5 and 24 h after the last injection. RNase protection assay and Western blot analysis revealed that all antidepressant drugs elicited an anatomically specific increase in FGF2 mRNA and protein. The increase in FGF2 mRNA after a single injection was seen only at 5 h after the injection and was restricted to the entorhinal cortex, whereas the effect of the long-term treatments lasted up to 24 h and occurred in the entire cortex and hippocampus. Immunohistochemical analysis of FGF2 immunoreactivity was carried out to investigate which cell types responded to the antidepressant treatments. DMI and MIA increased FGF2 proteins predominantly in neurons of layer V throughout the cerebral cortex and in some neurofilament-positive cells of the hippocampus. FLU increased FGF2 immunoreactivity mainly in neurofilament-positive cells of the hippocampus. These findings may explain the therapeutic efficacy of antidepressants in affective disorders.

Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures

“…Yet, a number of medications and drugs have been shown to increase the expression of multiple growth factors. Antidepressants for example, have been shown to increase the expression of IGF-1, BDNF, and FGF-2 (Duman et al, 1997;Mallei et al, 2002;Khawaja et. al., 2004;Maragoli et al, 2004).…”

“…Similarly, BDNF has been shown to inhibit, apoptosis in hippocampal neurons Johnson-Farley et al, 2006). Expression of FGF-2, a less well characterized growth factor, has also been reported to be increased by antidepressants in cortex and hippocampus (Mallei et al, 2002;Maragnolli et al, 2004). The peptide has been demonstrated to have a role in stimulating hippocampal neurogenesis (Palmer et al, 1999) and, and in some model systems, has been reported to have neurotrophic actions.…”

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

“…Antidepressants increase the expression of these neurotrophic/growth factors [15,16,17,18,19] and BDNF and VEGF mediate the action of antidepressants on neurogenesis in the adult DG in vivo [19,20]. However, it remains unclear whether FGF2, GDNF and IGF mediate the effect of antidepressants on neurogenesis on the adult DG.…”

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

“…Antidepressant drugs and chronic electroconvulsive shock treatment may increase the expression of fibroblast growth factor-2 (FGF-2) in frontal cortices and hippocampus (Mallei et al, 2002;Maragnoli et al, 2004), suggesting that potentially also the FGF-2 expression could mediate the antidepressant effects, in line with these results chronic antidepressant treatment increases neurogenesis in adult rat hippocampus (Duman et al, 2001) and recently evidence has been provided that increased neurogenesis might play a role in the mechanism of antidepressant drug action (Santarelli et al, 2003). Depression is associated with reduced cortical thickness and neuronal size (Rajkowska et al, 1999) and may even be caused by cortical neuronal atrophy with the accompanying loss of neuronal communication in prefrontal cortex.…”