Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression

Abstract

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are proteins involved in neuronal survival and plasticity of dopaminergic, cholinergic and serotonergic neurons in the central nervous system. Since decreased size and impaired function of some neuronal populations may be relevant in depression it has been hypothesized that these molecules may have a functional role in the pathophysiology as well as treatment of depression. Using an animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls, the Flinders Resistant Line (FRL), we investigated the effects of chronic lithium treatment on brain NGF, BDNF and GDNF. Lithium was administered as food supplementation during 6 wk. NGF, BDNF and GDNF measurements were performed by enzyme-linked immunosorbent assay (ELISA). Lithium altered the brain concentrations of neurotrophic factors in the hippocampus, frontal cortex, occipital cortex and striatum. Moreover, the changes were different in the two rat strains. Our data support the notion that neurotrophic factors play a role in depression and in the mechanism of the action of lithium.

BDNF in schizophrenia, depression and corresponding animal models

“…Effect of chronic lithium treatment on brain BDNF was also investigated in the 'depressed' FSL rats and their controls, the FRL line; significantly altered constitutive brain concentrations of BDNF were found. 100 In contrast to the work cited above that used a 7-, 14-or 28-day lithium treatment period, 25 we did not see changed BDNF levels in the hippocampus in any of the rat strains after 42 days of lithium. We also did not observe the reported increased BDNF levels in the frontal cortex.…”

Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 α and AP-2 β in Frontal Cortex of Rats Treated with Lithium for 6 Weeks

“…Lithium fed 42 days to Flinders-sensitive line rats produced significant changes in brain levels of NGF, BDNF, and GDNF compared to Flinders-resistant line rats (Angelucci et al, 2003). Changes in BDNF can rectify behavioral deficits in an animal model of depression in learned helplessness and in the forced swim test (Siuciak et al, 1997).…”

“…There is evidence that a clinically relevant lithium level in plasma produces beneficial effects in animal models of depression (Angelucci et al, 2003). Lithium fed 42 days to Flinders-sensitive line rats produced significant changes in brain levels of NGF, BDNF, and GDNF compared to Flinders-resistant line rats (Angelucci et al, 2003).…”

Driving GDNF expression: The green and the red traffic lights

“…GDNF levels may be altered by anti-depressants (Hisaoka et al, 2001), anti-psychotics (Shao et al, 2006) and mood stabilizers (Angelucci et al, 2003;Castro et al, 2005). It has been hypothesized that these drugs might exert their beneficial action by regulating the synthesis and/or release of neurotrophic factors (Angelucci et al, 2003;Saarelainen et al, 2003;Hashimoto et al, 2004).…”

“…It has been hypothesized that these drugs might exert their beneficial action by regulating the synthesis and/or release of neurotrophic factors (Angelucci et al, 2003;Saarelainen et al, 2003;Hashimoto et al, 2004). Anti-depressants significantly increase GDNF mRNA expression and GDNF release in a time-and concentrationdependent manner in C6 cells, and amitriptyline treatment also increases GDNF mRNA expression in rat astrocytes (Hisaoka et al, 2001).…”