ATF2, A Member of the CREB/ATF Family of Transcription Factors, in Chronic Stress and Consequent to Antidepressant Treatment: Animal Models and Human Post-Mortem Brains

Laifenfeld, Daphna; Karry, Rachel; Grauer, Ettie; Klein, Ehud; Ben‐Shachar, Dorit

doi:10.1038/sj.npp.1300357

Cited by 20 publications

(10 citation statements)

References 64 publications

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“…Bcl-2L1 can inhibit apoptosis following withdrawal of growth factors [40], and the smaller variant, Bcl-X S , encodes a protein that inhibits the ability of Bcl-2 to enhance survival of growth factor-deprived cells [40]. Previous work has shown that lithium up-regulates Bcl-X L [41] and Bcl-2 in frontal cortex, hippocampus and striatum [42]. It has been suggested that this action is part of its efficacy in provision of neuroprotective effect to the brain [43].…”

Section: Additional Genes Down-regulated By Lithiummentioning

confidence: 98%

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Fatemi

Reutiman

Folsom

2009

Biochemical Society Transactions

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Bipolar disorder is a debilitating disorder of the brain with a lifetime prevalence of 1.0% for bipolar I, 1.1% for bipolar II disorder and 2.4-4.7% for subthreshold bipolar disorder. Medications, including lithium, have demonstrated efficacy in the treatment of bipolar disorder, but their molecular targets and mode of action are largely unknown. A few studies have begun to shed light on potential targets of lithium treatment that may be involved in lithium's therapeutic effect. We have recently conducted a microarray study of rat frontal cortex following chronic treatment (21 days) with lithium. Chronic treatment with lithium led to a significant (at least 1.5-fold) down-regulation of 151 genes and up-regulation of 57 genes. We discuss our results in the context of previous microarray studies involving lithium and gene-association studies to identify key genes associated with chronic lithium treatment. A number of genes associated with bipolar disorder, including Comt (catechol-O-methyltransferase), Vapa (vesicle-associated membrane protein-associated protein A), Dtnb (dystrobrevin beta) and Pkd1 (polycystic kidney disease 1), were significantly altered in our microarray dataset along with genes associated with synaptic transmission, apoptosis and transport among other functions.

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Section: Additional Genes Down-regulated By Lithiummentioning

confidence: 98%

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Fatemi

Reutiman

Folsom

2009

Biochemical Society Transactions

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“…However, a causal link between CREB, antidepressants, enhanced hippocampal neurogenesis and depression-related behaviors remains to be established. Other transcription factors of the CREB/activating transcription factor family are also known to be regulated by stress and antidepressant treatments [112], however, their relevance to the neurogenic changes observed following these treatments is at present unknown.…”

Section: Transcription Factorsmentioning

confidence: 99%

Regulation of adult hippocampal neurogenesis: relevance to depression

Vaidya¹,

Fernandes²,

Jha³

2007

Expert Review of Neurotherapeutics

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Recent hypotheses suggest that depression may involve an inability to mount adaptive structural changes in key neuronal networks. In particular, the addition of new neurons within the hippocampus, a limbic region implicated in mood disorders, is compromised in animal models of depression. Adult hippocampal neurogenesis is also a target for chronic antidepressant treatments, and an increase in adult hippocampal neurogenesis is implicated in the behavioral effects of antidepressants in animal models. The 'neurogenic' hypothesis of depression raises the intriguing possibility that hippocampal neurogenesis may contribute to the pathogenesis and treatment of depressive disorders. While there remains substantial debate about the precise relevance of hippocampal neurogenesis to mood disorders, this provocative hypothesis has been the focus of many recent studies. In this review, we discuss the pathways that may mediate the effects of depression models and antidepressants on adult hippocampal neurogenesis, and the promise of these studies in the development of novel antidepressants.

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“…This has prompted reclassification of these proteins as more general "adaptive response" transcription factors (Cho et al, 2001;Lu et al, 2007). There is one report of alterations in ATF2 levels in frontal cortex after chronic administration of antidepressants (Laifenfeld et al, 2004). However, virtually nothing is known about the function of these transcription factors in the nucleus accumbens or in response to drugs of abuse or behavioral stress.…”

Section: Introductionmentioning

confidence: 99%

Induction of Activating Transcription Factors (ATFs) ATF2, ATF3, and ATF4 in the Nucleus Accumbens and Their Regulation of Emotional Behavior

Green¹,

Alibhai²,

Unterberg³

et al. 2008

J. Neurosci.

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Previous research has shown that cAMP response element (CRE) binding protein (CREB) in the nucleus accumbens gates behavioral responses to emotional stimuli. For example, overexpression of CREB decreases anxiety, sucrose preference, and sensitivity to drugs of abuse and increases depression-like behavior, whereas blocking CREB via overexpression of inducible cAMP early repressor (ICER) or other dominant-negative inhibitors of CRE-mediated transcription has the opposite effects. However, CREB and ICER are but two members of a larger family of leucine zipper-containing transcription factors composed of multiple products of the creb, crem (cAMP response element modulator), and atf (activating transcription factor) genes. We demonstrate here that ATF2, ATF3, and ATF4 are each robustly induced in the nucleus accumbens and dorsal striatum by restraint stress or by amphetamine administration. In contrast, little induction is seen for ATF1 or CREM. Using viral-mediated gene transfer, we show that ATF2 overexpression in nucleus accumbens produces increases in emotional reactivity and antidepressant-like responses, a behavioral phenotype similar to that caused by dominant-negative antagonists of CREB. In contrast, ATF3 or ATF4 overexpression in nucleus accumbens decreases emotional reactivity and increases depression-like behavior, consistent with the behavioral phenotype induced by CREB. Because amphetamine and stress induce ATF2, ATF3, and ATF4 in nucleus accumbens, and overexpression of these transcription factors in this brain region in turn alters behavioral responsiveness to amphetamine and stress, our findings support novel roles for these ATF family members in regulating emotional behavior.

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ATF2, A Member of the CREB/ATF Family of Transcription Factors, in Chronic Stress and Consequent to Antidepressant Treatment: Animal Models and Human Post-Mortem Brains

Cited by 20 publications

References 64 publications

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Regulation of adult hippocampal neurogenesis: relevance to depression

Induction of Activating Transcription Factors (ATFs) ATF2, ATF3, and ATF4 in the Nucleus Accumbens and Their Regulation of Emotional Behavior

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