The Role of Protein Kinase A in Anxiety Behaviors

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

doi:10.1159/000444880

Cited by 20 publications

(13 citation statements)

References 185 publications

(207 reference statements)

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“…Recent work has suggested that activation of the IP receptor, a cAMP-dependent PKA pathway, may be sufficient to drive stress responses in vivo (61). Stimulation of this pathway leads to activation of CRE (cAMP-responsive elements) binding proteins in the nucleus to synthesize new proteins that alter fear learning and memory formation (61). Increased expression of prostacyclin also appeared to exert detrimental effects on other cognitive tests.…”

Section: Discussionmentioning

confidence: 99%

Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease

Womack

Vollert

Nwoko

et al. 2020

Preprint

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies, while epidemiological and experimental evidence suggests that the use of anti-inflammatory agents may be neuroprotective. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is wellestablished that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid disease pathologies. Mice overexpressing both amyloid and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of amyloid accumulation in the brain and selectively increased the production of soluble amyloid-β 42. PGI2 damaged the microvasculature through alterations in vascular length and branching; amyloid expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.

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Section: Discussionmentioning

confidence: 99%

Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease

Womack

Vollert

Nwoko

et al. 2020

Preprint

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“…DL PA is significantly lower in depressed compared with non‐depressed COPD patients, and anxiety is highly prevalent among asthma patients, where it is associated with more exacerbations, more hospital readmissions, and poorer asthma control . The molecular mechanisms responsible for anxiety are not well understood and might involve abnormal neural processing of stimuli . Therefore, it is possible that asthma patients avoid exercise for fear of triggering symptoms, which leads to a sustained overall aversion to exercise .…”

Section: Discussionmentioning

confidence: 99%

Factors associated with daily life physical activity in patients with asthma

Hennegrave

Fry

Behal

et al. 2018

Health Science Reports

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“…There is evidence that impaired generation and functional integration of adult-born DG neurons as well as dys-regulation of cAMP/PKA-signaling play a significant role in the pathophysiology of neuropsychiatric and neurodegenerative disorders such as anxiety, depression, and Alzheimer’s disease 34 – 38 . It will be interesting to explore if and how dys-regulation of SOX11 phosphorylation contributes to those pathologies.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

Balta

Schäffner

Wittmann

et al. 2018

Sci Rep

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The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11’s activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11’s transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.

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The Role of Protein Kinase A in Anxiety Behaviors

Cited by 20 publications

References 185 publications

Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease

Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease

Factors associated with daily life physical activity in patients with asthma

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

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