Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review

Keil, Margaret F.; Briassoulis, George; Stratakis, Constantine A.; Wu, Tao

doi:10.3389/fendo.2016.00083

Cited by 33 publications

(23 citation statements)

References 96 publications

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“…With respect to the PTSD-like EBR group, this shared module was associated with downregulation of GPCR signaling, synaptic signaling/transmission, GABAβ receptor activation, and exploration behavior, as well as decreased regulation of insulin secretion by glucagonlike peptide 1, protein kinase A (PKA) signaling, and cAMP metabolic process. GPCR signaling, PKA signaling, and cAMP metabolic processes are ubiquitous and involved in signaling transduction; in the cell, cAMP targets PKA, which serves as the principal effector mechanism for GPCRs linked to adenylate cyclase [73]. The cAMP/PKA signaling pathway is involved in the regulation of glucose homeostasis [74] and relevant to the decreased regulation of insulin secretion by glucagon-like peptide 1.…”

Section: Amygdalamentioning

confidence: 99%

“…The cAMP/PKA signaling pathway is involved in the regulation of glucose homeostasis [74] and relevant to the decreased regulation of insulin secretion by glucagon-like peptide 1. Additionally, the cAMP/PKA signaling pathway plays an essential, evolutionarily conserved role in the mediation of neural processing of threat-related stimuli (i.e., fear learning), consolidation of fear memory, and fear-related behavioral response in the amygdala [73]. Targeted activation of cAMP/PKA signaling in the lateral amygdala has been shown to increase neuronal excitability and lead to generalized fear [75], while targeted inhibition of cAMP/PKA activity in the lateral amygdala immediately after fear conditioning impaired fear memory retention [76].…”

Section: Amygdalamentioning

confidence: 99%

“…Targeted activation of cAMP/PKA signaling in the lateral amygdala has been shown to increase neuronal excitability and lead to generalized fear [75], while targeted inhibition of cAMP/PKA activity in the lateral amygdala immediately after fear conditioning impaired fear memory retention [76]. Additionally, stress modulates fear memories; β-adrenoceptor-mediated activation of the cAMP/PKA pathway has been shown to enhance fear memory consolidation, and glucocorticoids (GCs) interact with the noradrenergic signaling pathway to modulate this activation in the basolateral amygdala (BLA) [73]. Targeted inhibition of either β-adrenoceptor or cAMP/PKA in the BLA before or immediately post inhibitory avoidance training has been shown to block memory consolidation and administering a GR antagonist before this training was able to block the noradrenergic-dependent enhancement of memory retention [77].…”

Section: Amygdalamentioning

confidence: 99%

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Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

Kim

Uddin

2020

Biol Sex Differ

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Background: While post-traumatic stress disorder (PTSD) is defined by behavioral/cognitive symptoms most directly relevant to brain function, it can be considered a systemic disorder characterized by a distinct inability to reinstate homeostasis after trauma. Methods: In this study, we conducted a secondary analysis of gene expression profiles in key PTSD-relevant tissues, namely blood, amygdala, and hippocampus, from a rat model of PTSD, to identify sex-specific and shared processes associated with individual differences in response to recent trauma exposure. Results: Our findings suggest both shared and sex-specific mechanisms underlying individual differences associated with vulnerability and resilience to trauma in hippocampus, amygdala, and blood. By disentangling cell composition from transcriptional changes, we found higher proportions of hippocampal oligodendrocytes in the PTSD-like, extreme behavioral response (EBR) group for both sexes and also identified modules for transcriptional activity associated with group differences (i.e., response to trauma) in the hippocampus that appeared to be sex-specific. By contrast, we found prominent sex differences, but no group differences, in amygdalar cell composition, and both shared and sex-specific modules representing PTSD-relevant transcriptional activity in the amygdala. Across amygdala and hippocampus, both sex-specific and shared processes were relevant to an overarching framework for EBR implicating disrupted TNFα/NFκΒ signaling and excitatory/inhibitory imbalance in dysregulated synaptic/structural plasticity with important implications for fear learning and memory. Our main finding in peripheral blood was consistent with the human literature and identified wound healing processes and hemostasis to be upregulated in the resilient, minimal behavioral response (MBR) group across sexes, but disrupted in a sexually dimorphic manner in the EBR group. Conclusion: In contrast to the varied characterization of the PTSD-like EBR group, characterization of MBR across blood, amygdala, and hippocampus suggests a common theme of upregulated wound healing and extracellular matrix (ECM) remodeling shared between sexes. In all, we identified differential oligodendrocyte proportions in hippocampus between PTSD-like EBR and resilient MBR, and identified processes and pathways that characterize the EBR and MBRassociated transcriptional changes across hippocampus, amygdala, and blood. The sex-specific mechanisms involved in EBR may contribute to the pronounced disparity in risk for PTSD, with women much more likely to develop PTSD.

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Section: Amygdalamentioning

confidence: 99%

Section: Amygdalamentioning

confidence: 99%

Section: Amygdalamentioning

confidence: 99%

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Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

Kim

Uddin

2020

Biol Sex Differ

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“…The intact heterotetrameric form arrests the biological function of PKA under physiological conditions. Once the intracellular cAMP level is elevated, this secondary messenger could directly bind the regulatory subunits of PKA to release its catalytic subunits, leading to phosphorylate their downstream targets for responding to cellular stresses [69]. Notably, the PKA catalytic subunit can interact with and directly phosphorylate AMPKα at the Ser173 residue, thus blocking its activating phosphorylation at Thr172 by other upstream kinases, such as LKB1.…”

Section: Functions Of Ampk Signaling Components In Tumorigenesismentioning

confidence: 99%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer.

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“…Also, individuals with anxiety disorders exhibit a “vigilance-avoidance” pattern of attention. Finally, stress-induced plasticity within the amygdala is involved in the transition from normal vigilance responses to emotional reactivity, fear overgeneralization, and deficits in fear inhibition resulting in pathological anxiety and conditions, such as panic and depression ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Discriminating between Anxious and Non-Anxious Subjects Using the Toronto Hospital Alertness Test

et al. 2017

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BackgroundAlertness designates the internal feeling of wakefulness or arousal and is often described to be linked to the level of anxiety. An adequate level of anxiety favoring the alertness needed to deal with a faced specific situation efficiently; too much anxiety can result in failure to process information and respond appropriately. Thus, it would be of interest to verify if different alertness profiles can be observed depending on anxiety level. The Toronto Hospital Alertness Test (THAT) is a test designed to measure alertness. The present survey’s aim is to verify if the THAT allows observing different alertness profile between self-described anxious and non-anxious subjects.MethodsSubjects >18 years were selected from online databases in three countries (Canada, USA, and UK). All respondents filled in a Hospital Anxiety Depression Scale questionnaire, and only those self-classified as anxious or non-anxious (HAD-A ≥11 or ≤7, respectively) took part to the survey and were asked to complete the THAT.ResultsAmong 616 respondents retained in the survey, 414 were self-assessed as anxious and 202 as non-anxious. The mean THAT score for anxious and non-anxious subjects was 21.4 and 38.9, respectively. A receiver operating characteristic (ROC) curve of THAT scores indicated that a threshold score of 30 was required to achieve good sensitivity (86.7%) and specificity (88.6%), with good discriminatory power [an area under the curve (AUC) of 0.938]. As age was determined to be a potential confounder, subjects were age-matched giving a ROC with an AUC of 0.931, with good sensitivity (88.5%) and specificity (89.3%), and the threshold remaining at 30. The internal reliability of THAT in anxious subjects was good (Cronbach alpha = 0.84).LimitationsNo independent verification of anxious or non-anxious status or other eligibility criteria was done.ConclusionThe alertness profiles of self-defined anxious and non-anxious subjects observed on THAT are different. Based on a subject’s alertness profile, it is possible to discriminate between self-defined anxious and non-anxious, using THAT, with good specificity and sensitivity at a threshold score of 30.

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Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review

Cited by 33 publications

References 96 publications

Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Discriminating between Anxious and Non-Anxious Subjects Using the Toronto Hospital Alertness Test

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