Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice

Pizarro, José María Sánchez-Marín; Lumley, Lucille A.; Medina, Wilma; Robison, Christopher L.; Chang, Wenling E.; Alagappan, Arun; Bah, Mariama J.; Dawood, Mustansir Y.; Shah, Jigar; Mark, Brian L.; Kendall, N.; Smith, Mark A.; Saviolakis, George A.; Meyerhoff, James L.

doi:10.1016/j.brainres.2004.06.085

Cited by 184 publications

(120 citation statements)

References 72 publications

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“…Results have shown that, after three weeks, stress induced a pronounced decrease in BDNF expression in the hippocampus but not in the cortex confirming previous reports which found that chronic restraint or social defeat stress caused downregulation of BDNF in the same brain region (Haenisch et al, 2009). In addition, our findings are in line with those of Pizarro and co-workers who found using in situ hybridization, that a brief (10 min) exposure to intense social stress significantly decreased BDNF mRNA expression in the hippocampus and amygdala 24 h after social defeat when compared to control (naive) mice (Pizarro et al, 2004). Also, our findings agree with those of Alfonso and colleagues, who had shown that when mice were subjected to repeated restraint stress, hippocampal BDNF messengers were down-regulated as measured by RT-PCR (Alfonso et al, 2006).…”

Section: Discussionsupporting

confidence: 92%

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Bahí

Chandrasekar

Dreyer

2014

Psychoneuroendocrinology

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Summary Several lines of evidences suggest that the brain-derived neutrophic factor (BDNF) is implicated in the pathophysiology of depression. However, the molecular mechanisms are not fully understood. In the current study we aimed to investigate how genetic modulation of BDNF in the hippocampus using microRNa124a (miR124a)-expressing lentiviral vectors (LV) might affect depression-like behavior in adult rats. For this purpose, we assessed the expression level of miR124a and its direct target BDNF in the hippocampus and the cortex after 21-days exposure to social defeat stress. Results demonstrated that miR124a was up-regulated in the hippocampus but not in the cortex. In contrast, and as expected, BDNF transcripts were down-regulated. In a different set of experiments, male Wistar rats received bilateral intra-hippocampal or intracortical infusions of BDNF-and miR124a-expressing lentiviral vectors and depression-like behavior was assessed after 21-days social defeat stress using the novelty suppressed feeding, the sucrose preference and the forced swim tests. The results indicated that miR124a overexpression exacerbated depression-like behavior. However, an anti-depressant like effect was observed when BDNF or miR124a-silencers (siR124a) were injected into the hippocampus. Importantly, when expressed into the cortex, LV-miR124a, LV-siR124a and LV-BDNF had no effect on depression. Our findings indicate that hippocampal miR124a and its direct target BDNF play an important role in depression-like behavior. Taken together, the current results reveal, for the first time, a potential molecular regulation of miR124a on BDNF, and the pronounced behavioral consequences of this regulation shed light on the mechanisms underlying BDNF anti-depressant potential. #

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Section: Discussionsupporting

confidence: 92%

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Bahí

Chandrasekar

Dreyer

2014

Psychoneuroendocrinology

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“…Both of these manipulations were found to induce significant decreases in hippocampal levels of BDNF mRNA, with greatest reductions occurring in the dentate gyrus, CA1 and CA3 pyramidal cell layers of the hippocampus. [20][21][22][23] Similar findings have been reported using alternative stressors, such as social isolation, 24 social defeat in mice, 25 chronic swim stress 26 and exposing rats to a cue paired previously with an electric shock. 27 Furthermore, a 24 h period of maternal separation leads to the emergence of a depressive-like phenotype and subnormal hippocampal BDNF expression later in adult life, as well as attenuated stress-induced BDNF alterations.…”

Section: Preclinical Evidencesupporting

confidence: 72%

Is it time to reassess the BDNF hypothesis of depression?

2007

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The brain-derived neurotrophic factor (BDNF) hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and that its restoration may underlie the therapeutic efficacy of antidepressant treatment. While this theory has received considerable experimental support, an increasing number of studies have generated evidence which is not only inconsistent, but also directly contradicts the hypothesis. This article provides a critical review of the clinical and preclinical studies which have been responsible for this controversy, outlining pharmacological, behavioural and genetic evidence which demonstrates the contrasting role of BDNF in regulating mood and antidepressant effects throughout the brain. I will also review key studies, both human and animal, which have investigated the association of a BDNF single-nucleotide polymorphism (Val66Met) with depression pathogenesis, and detail the number of inconsistencies which also afflict this novel area of BDNF research. The article will conclude by discussing why now is a critical time to reassess the original BDNF hypothesis of depression, and look towards the formation of new models that can provide a more valid account of the complex relationships between growth factors, mood disorders and their treatment.

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“…Expression of BDNF changes in response to different stressors and depends on the brain structure studied (Pizarro et al, 2004;Xu et al, 2004;Rosenbrock et al, 2005). The increase in BDNF expression found in our experiment could be a synergistic effect produced by LPS toxicity and stress through the loss of GABAergic neurons rather than being produced by stress directly.…”

Section: Discussionmentioning

confidence: 53%

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Pablos¹,

Villarán²,

Argüelles³

et al. 2006

J. Neurosci.

190

176

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Inflammation could be involved in some neurodegenerative disorders that accompany signs of inflammation. However, because sensitivity to inflammation is not equal in all brain structures, a direct relationship is not clear. Our aim was to test whether some physiological circumstances, such as stress, could enhance susceptibility to inflammation in the prefrontal cortex (PFC), which shows a relative resistance to inflammation. PFC is important in many brain functions and is a target for some neurodegenerative diseases. We induced an inflammatory process by a single intracortical injection of 2 g of lipopolysaccharide (LPS), a potent proinflammogen, in nonstressed and stressed rats. We evaluated the effect of our treatment on inflammatory markers, neuronal populations, BDNF expression, and behavior of several mitogen-activated protein (MAP) kinases and the transcription factor cAMP response element-binding protein. Stress strengthens the changes induced by LPS injection: microglial activation and proliferation with an increase in the levels of the proinflammatory cytokine tumor necrosis factor-␣; loss of cells such as astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and neurons, studied by neuronal-specific nuclear protein immunohistochemistry and GAD67 and NMDA receptor 1A mRNAs expression by in situ hybridization. A significant increase in the BDNF mRNA expression and modifications in the levels of MAP kinase phosphorylation were also found. In addition, we observed a protective effect from RU486 [mifepristone (11␤-[p-(dimethylamino)phenyl]-17␤-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)], a potent inhibitor of the glucocorticoid receptor activation. All of these data show a synergistic effect between inflammation and stress, which could explain the relationship described between stress and some neurodegenerative pathologies.

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Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice

Cited by 184 publications

References 72 publications

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Is it time to reassess the BDNF hypothesis of depression?

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

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