Age‐dependent effects of chronic stress on brain plasticity and depressive behavior

Tóth, É.; Gersner, Roman; Wilf-Yarkoni, Adi; Raizel, Hagit; Dar, Dalit E.; Richter‐Levin, Gal; Levit, Ofir; Zangen, Abraham

doi:10.1111/j.1471-4159.2008.05642.x

Cited by 182 publications

(165 citation statements)

References 58 publications

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“…Furthermore, JNK1 is also involved in AMPA receptor internalization in the nucleus accumbens after cocaine challenge in sensitized rats (Boudreau et al, 2007). Moreover, because JNK2/3 signaling is activated upon stress and neuropathological stimulation (Bogoyevitch and Kobe, 2006), and both JNK1 and JNK2 phosphorylate Hes-1 at Ser-263, the present result is also consistent with the finding that chronic mild stress decreases GluR1 expression in rat prefrontal cortex and hippocampus (Toth et al, 2008). Whether stress also upregulates Hes-1 expression and decreases calcium influx requires further investigation.…”

Section: Discussionsupporting

confidence: 81%

JNK1 Inhibits GluR1 Expression and GluR1-Mediated Calcium Influx through Phosphorylation and Stabilization of Hes-1

Lin

Lee²

2012

J. Neurosci.

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The GluR1 subunit of the AMPA receptor plays an important role in excitatory synaptic transmission and synaptic plasticity in the brain, but the regulation mechanism for GluR1 expression is largely unknown. Hairy and enhancer of split 1 (Hes-1) is a mammalian transcription repressor that regulates neuronal differentiation and development, but the role of Hes-1 in differentiated neurons is also less known. Here, we examined the molecular mechanism in regulation of GluR1 expression in rat cultured cortical neurons. We found that Hes-1 suppressed GluR1 promoter activity and decreased GluR1 expression through direct binding to the N-box and through preventing Mash1/E47 from binding to the E-box of GluR1 promoter. We also found that Hes-1 could be regulated by c-Jun N-terminal kinase (JNK1). JNK1 directly phosphorylates Hes-1 at Ser-263. Furthermore, JNK1 phosphorylation of Hes-1 stabilized the Hes-1 protein and enhanced the suppressing effect of Hes-1 on GluR1 expression. These effects were demonstrated both in the soma and at the synapse. Moreover, this JNK1-mediated signaling pathway was found to inhibit AMPA-evoked calcium influx in cortical neurons and this regulation mechanism is Notch independent. Here, we provided the first evidence that Hes-1 plays an important role in synaptic function in differentiated neurons. We also identified a novel JNK1-Hes-1 signaling pathway that regulates GluR1 expression involved in synaptic function in rat cortical neurons.

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Section: Discussionsupporting

confidence: 81%

JNK1 Inhibits GluR1 Expression and GluR1-Mediated Calcium Influx through Phosphorylation and Stabilization of Hes-1

Lin

Lee²

2012

J. Neurosci.

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“…Interestingly, some of the effects of chronic CORT or stress exposure in adult animals do not appear to occur when the stress takes place during adolescence (Bourke and Neigh, 2011;Jankord et al, 2011;Xu et al, 2011). For example, male rodents exposed to chronic restraint or unpredictable stress in adolescence do not show reductions in hippocampal neurogenesis, as is observed in adult animals exposed to chronic stress (Barha et al, 2011;Toth et al, 2008). However, female rodents exposed to chronic stress in either adolescence or adulthood show reductions in neurogenesis (Barha et al, 2011).…”

Section: Introductionmentioning

confidence: 96%

Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats

Torregrossa

Xie

Taylor

2012

Neuropsychopharmacol

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Chronic stress during adolescence is associated with an increased risk for alcoholism and addictive disorders. Addiction is also associated with increased impulsivity, and stress during adolescence could alter cortical circuits responsible for response inhibition. Therefore, the present study determined the effect of chronic exposure to the stress hormone corticosterone (CORT) during adolescence on tests of impulsivity in adulthood and examined possible biochemical mechanisms. Male Sprague-Dawley rats were exposed to CORT by their drinking water during adolescence (post-natal day 30-50). The rats were then tested in adulthood to assess behavior on the 5-choice serial reaction time task (5CSRTT), stop-signal reaction time task (SSRTT), and the delay-discounting task, which differentially assess attention, impulsive action, and impulsive choice. Yohimbine-induced impulsivity on the 5CSRTT and biochemical analysis of the lateral orbital frontal cortex (lOFC) was also assessed owing to the ability of yohimbine to activate the hypothalamic-pituitary-adrenal axis and influence impulsivity. Adolescent CORT-treated rats were found to behave largely like controls on the 5CSRTT, but did show reduced premature responses when the intertrial interval was increased. Nevertheless, the CORT-treated rats tended to have more yohimbineinduced impulsive responses at low doses on this task, which was not found to be due to increased pCREB in the lOFC, but could be related to a higher expression/activity of the AMPA receptor subunit GluR1. Adolescent CORT-treated rats performed more accurately on the SSRTT, but showed greater impulsivity on the delay-discounting task, as indicated by steeper discounting functions. Therefore, adolescent CORT exposure reduced impulsive action but increased impulsive choice, indicating that chronic stress hormone exposure in adolescence can have long-term consequences on behavior.

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“…Indeed, plasma levels of CORT are altered in adult rats that were maternally separated or later exposed to CMS in early life (Francis et al, 2002;Lippmann et al, 2007;Toth et al, 2008). Obviously, the degree of stress plays an important role; rats that experienced long, but not short, maternal separation showed an increased elevation of CORT in response to acute stress in adulthood (Francis et al, 2002;Lippmann et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…CMS in adult rats reduces BDNF expression in the dorsal hippocampus (Grønli et al, 2006;Toth et al, 2008;Gersner et al, 2010) and causes reductions in sucrose preference, sexual behavior, and brain stimulation reward, indicating a state of anhedonia (Muscat and Willner, 1992;Grønli et al, 2006;Toth et al, 2008). Conversely, young rats show resilience to the anhedonic effect of CMS, and, unlike adult rats, their hippocampal BDNF levels remain intact (Toth et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

Taliaz

Loya²,

Gersner³

et al. 2011

J. Neurosci.

257

168

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Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

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Age‐dependent effects of chronic stress on brain plasticity and depressive behavior

Cited by 182 publications

References 58 publications

JNK1 Inhibits GluR1 Expression and GluR1-Mediated Calcium Influx through Phosphorylation and Stabilization of Hes-1

JNK1 Inhibits GluR1 Expression and GluR1-Mediated Calcium Influx through Phosphorylation and Stabilization of Hes-1

Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats

Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

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