Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock,

Abstract

This study examined the effects of footshock stress and reexposure to cues previously associated with footshock on expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus of male rats. Exposure to twenty 0.5-s 0.4-mA footshocks co-terminating withBrain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors, which also includes nerve growth factor and neurotrophins 3 and 4. BDNF as well as these other neurotrophins, plays an important role in neuronal growth and differentiation during development, and also contributes to the survival, function, and plasticity of neurons in the adult brain (Lewin and Barde 1996). Thus, through a variety of mechanisms in different brain regions, BDNF has been implicated in emergent phenomena such as learning and memory (Patterson et al. 1996;Mu et al. 1999) and even contributes to the modulation of overt behaviors such as aggression (Lyons et al. 1999). The ability of BDNF to influence these processes is related, in part, to the activity dependent regulation of BDNF expression in adult brain (Lewin and Barde 1996).BDNF is also thought to play a role in the cellular and behavioral responses to stress (Duman et al. , 2000. Exposure to physical stress, such as immobilization, downregulates BDNF expression in the hippocampus (Smith et al. 1995, Vaidya et al. 1997 (Duman et al. , 2000. Moreover, downregulation of BDNF could contribute to the hippocampal pathology observed in psychiatric disorders such as post-traumatic stress disorder (PTSD) and depression (Bremner et al. 2000;Mervaala et al. 2000;Vakili et al. 2000). This possibility is supported by the observation that these disorders are sensitive to stressful experiences (Breslau et al. 1995;Kendler et al. 2000). Based on these observations and findings, we became interested in determining whether psychological stress has a measurable impact on hippocampal BDNF expression similar to the effects of physical stressors that have been reported.We therefore tested the effects of psychological stress produced by exposures to cues previously paired with footshock on BDNF mRNA levels in the dentate gyrus of the hippocampus. We hypothesized that re-exposure to cues associated with footshock stress, as well as footshock itself, would decrease BDNF mRNA in the dentate gyrus. The results demonstrate that this type of psychological stress produces a heightened sensitivity to previously neutral cues that results in downregulation of BDNF, and suggest that psychological stress, such as that experienced in association with PTSD and depression, as well as other disorders, could result in decreased neurotrophic support of the hippocampus. MATERIAL AND METHODS AnimalsAdult male Sprague-Dawley rats were kept in a 12:12 h light-dark cycle (lights on at 7:00 A . M .) for 7-10 days before each experiment. The animals were housed two or three per cage and fed ad libitum. Experiments were conducted between 9:00 A . M . and 6:00 P . M . To control for possible effects of diurnal variation on hippoca...

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

“…In 1995, it was originally found that ADs increase the synthesis of BDNF (Nibuya et al, 1995). Later, several animal studies demonstrated that stress, an important factor in the etiology of depression, can decrease hippocampal BDNF levels (Smith et al, 1995;Nibuya et al, 1999;Rasmusson et al, 2002); conversely, chronic AD treatments could enhance BDNF expression in hippocampus (Larsen et al, 2008;Sillaber et al, 2008). Furthermore, infusion of BDNF into the midbrain or hippocampus induced AD-like effects in two separate depression models (Siuciak et al, 1997;Shirayama et al, 2002).…”

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

“…Emerging evidence further suggests that BDNF may play a key role in the pathophysiology of stress-related disorders. Lower hippocampal BDNF levels have been found subsequent to various stressors such as prenatal stress (Fumagalli et al, 2004), footshock stress (Rasmusson et al, 2002), postnatal stress (MacQueen et al, 2003;Roceri et al, 2004) and restraint stress (Smith et al, 1995;Vaidya et al, 1997;Xu et al, 2004). Also of interest is the fact that intrahippocampal administration of BDNF protects against stress-induced impairments in spatial learning and memory and LTP (Radecki et al, 2005).…”

Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects

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