Differential distribution of PDE4B splice variant mRNAs in rat brain and the effects of systemic administration of LPS in their expression

Reyes-Irisarri, Elisabet; Pérez-Torres, S.; Miró, Xavier; Martı́nez, Emili; Puigdomènech, Pere; Palacios, J.M.; Mengod, Guadalupe

doi:10.1002/syn.20459

Cited by 33 publications

(33 citation statements)

References 37 publications

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“…In our group we have previously reported a selective increase in PDE4B2 mRNA levels in LPS-treated rats (Reyes-Irisarri et al, 2008) and in brain circumventricular organs of LPS-treated mice (Johansson et al, 2011). All this together points to the involvement of the PDE4B subfamily in events related to neuroinflammation.…”

Section: Discussionmentioning

confidence: 73%

Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis

Sanabra

Johansson

Mengod

2013

Journal of Chemical Neuroanatomy

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Section: Discussionmentioning

confidence: 73%

Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis

Sanabra

Johansson

Mengod

2013

Journal of Chemical Neuroanatomy

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“…Our analysis shows that several genes encoding for proteins belonging to the NF-kB, MAPK, STAT-JAK, and IRFs signaling pathways are induced in the CP during the acute-phase response. All of these pathways, together with others such as those mediated by cAMP (Reyes-Irisarri et al, 2008), participate in the development and regulation of innate and adaptative immune responses (Rawlings et al, 2004), and the CP, like the BBB endothelium , responds to peripheral LPS by activating some of these pathways. Termination of the CP response at 72 h may be, at least in part, a consequence of the negative feedback inhibition of STAT signaling by SOCS/CIS (Naka et al, 2005), as some of the genes encoding for proteins in this pathway are up-regulated after LPS administration.…”

Section: Proposed Model Of the Choroid Plexus Response To Peripheral mentioning

confidence: 99%

Kinetic Profile of the Transcriptome Changes Induced in the Choroid Plexus by Peripheral Inflammation

Marques

Sousa

Coppola

et al. 2009

J Cereb Blood Flow Metab

104

122

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The choroid plexus, being part of the blood-brain barriers and responsible for the production of cerebrospinal fluid, is ideally positioned to transmit signals into and out of the brain. This study, using microarray analysis, shows that the mouse choroid plexus displays an acute-phase response after an inflammatory stimulus induced in the periphery by lipopolysaccharide (LPS). Remarkably, the response is specific to a restricted number of genes (out of a total of 24,000 genes analyzed, 252 are up-regulated and 173 are down-regulated) and transient, as it returns to basal conditions within 72 h. The up-regulated genes cluster into families implicated in immune-mediated cascades and in extracellular matrix remodeling, whereas those down-regulated participate in maintenance of the barrier function. Importantly, several acute-phase proteins, whose blood concentrations rise in response to inflammation, may contribute to the effects observed in vivo after LPS injection, as suggested by the differential response of primary choroid plexus epithelial cell cultures to LPS alone or to serum collected from animals exposed to LPS. By modulating the composition of the cerebrospinal fluid, which will ultimately influence the brain parenchyma, the choroid plexus response to inflammation may be of relevance in brain homeostasis in health and disease.

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“…High levels of cytosolic cAMP lead to the activation of PKA and further induce the phosphorylation of transcription factors, such as CREB and cAMP-dependent transcription factor-1 (ATF-1) to drive cAMP-driven genes, which involve in the regulation of proinflammatory and antiinflammatory pathways (as shown in Figure 2).However, the diferential distribution of the four PDE4 subtypes (PDE4A-D) in the brain [85] may be atributed to the diferent regulation of cAMP-mediated signaling in CNS. PDE4A and PDE4D are highly expressed in the cortex, olfactory bulb, hippocampal formation, and brainstem, whereas PDE4B is mainly expressed in the amygdala, striatum, and hypothalamus [86][87][88]. By contrast, PDE4C exhibits a distribution diferent from those of PDE4A and PDE4D and appears to be limited to the thalamus and cerebellum [89,90].…”

Section: Pde4 and The Distribution Of Its Subtypes In Cnsmentioning

confidence: 99%

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

Wang¹,

Wang²,

Li³

et al. 2017

Mechanisms of Neuroinflammation

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Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. Cyclic adenosine monophosphate (cAMP) is a critical regulator of microglia homeostasis; as the predominant negative modulator of cyclic AMP signaling within microglia, and phosphodiesterase 4 (PDE4) represents a promising target for modulating immune function. The approach for pharmacological manipulation of cAMP levels using specifc PDE4 inhibitors provokes an ant-iinflammatory response. Specifcally, PDE4 inhibitors have recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and psychiatric diseases. Mechanistically, PDE4 inhibitors produce an anti-inflammatory and neuroprotection efect by increasing the accumulation of cAMP and activating protein kinase A (PKA), the signaling pathway of which is thought to play an important role in the development of psychiatric disorders. This chapter reviews present knowledge of the relationship between neuroinflammation and classical psychiatric disorders (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia) and demonstrates the signaling pathways that underlie the use of PDE4 inhibitors in neuroinflammation. In addition, among the four subtypes (A-D) of PDE4, it remains unclear which one exerts suppressive efects on neuroinflammation. Understanding how PDE4 and neuroinflammation interact can reveal pathogenic clues and help target new preventive and symptomatic therapies for psychiatric illness.

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Differential distribution of PDE4B splice variant mRNAs in rat brain and the effects of systemic administration of LPS in their expression

Cited by 33 publications

References 37 publications

Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis

Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis

Kinetic Profile of the Transcriptome Changes Induced in the Choroid Plexus by Peripheral Inflammation

Reducing Neuroinflammation in Psychiatric Disorders: Novel Target of Phosphodiesterase 4 (PDE4) and Developing of the PDE4 Inhibitors

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