Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide

Armstrong, Brian; Abad, Catalina; Chhith, Seririthanar; Cheung-Lau, Gardenia; Hajji, O.E.; Nobuta, Hiroko; Waschek, James A.

doi:10.1016/j.neuroscience.2007.09.084

Cited by 104 publications

(92 citation statements)

References 43 publications

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“…Thus our data clearly demonstrate a functional role of GIP/GIPR signalling in nerve regeneration. Interestingly, very recently it was shown that also the cognate peptide PACAP is critically involved in proper nerve regeneration by controlling lesion-induced immune responses (Armstrong et al, 2008).…”

Section: Impaired Spontaneous Nerve Regeneration In Mice Lacking Giprmentioning

confidence: 99%

Glucose‐dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion‐affected expression, and impaired regenerative axonal growth

Buhren

Gasis

Thorens

et al. 2009

J of Neuroscience Research

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Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice.

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Section: Impaired Spontaneous Nerve Regeneration In Mice Lacking Giprmentioning

confidence: 99%

Glucose‐dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion‐affected expression, and impaired regenerative axonal growth

Buhren

Gasis

Thorens

et al. 2009

J of Neuroscience Research

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“…Numerous results indicate that it exerts growth factor-like activities in the brain during development, regeneration, and tumorigenesis (6)(7)(8)(9)(10). Indeed, considerable data indicate that PACAP, mainly via PAC1, regulates neural cell proliferation, survival, axon regeneration and oligodendrocyte progenitor proliferation and maturation (6)(7)(8)(9)(11)(12)(13).…”

mentioning

confidence: 99%

Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis

Tan

Abad

Lopez

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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autoimmunity ͉ regulatory T cell ͉ inflammation ͉ knock-out ͉ multiple sclerosis M ultiple sclerosis (MS) afflicts over 2.5 million people worldwide, with women affected 3 times more frequently than men. Although its precise etiology is unknown, MS has been characterized as a Th1-and/or Th17-mediated autoimmune disease (1). Experimental autoimmune encephalomyelitis (EAE), commonly induced by immunizing with various myelin autoantigens, is an experimental model of MS that allows investigators to study the pathogenesis of this disease and to test new therapeutic strategies (2). Indeed EAE is an acute or chronic-relapsing inflammatory and demyelinating autoimmune disease with resemblance to MS in humans. The major features shared are the autoimmune destruction of the myelin sheaths of the nerve fibers, the presence of multiple CNS lesions with a predominantly perivascular location, and a temporal maturation of lesions from inflammation through demyelination, and finally axonal destruction.Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a 38-amino-acid neuropeptide identified by Arimura and colleagues in 1989 from ovine hypothalamus (3) and belongs to the secretin family. Its closest family member is vasoactive intestinal peptide (VIP), to which it is 68% identical. The actions of PACAP and VIP are mediated by 3 heterotrimeric G protein-coupled receptors, 1 (PAC1), which is highly specific for PACAP except for 1 splice variant (4), and 2 (VPAC1 and VPAC2) which interact with PACAP and VIP with equally high affinity (5). Although PACAP is widely distributed in the CNS and peripheral nervous system and is classically viewed as a neurotransmitter, it is capable of eliciting a broad spectrum of biological actions (5). Numerous results indicate that it exerts growth factor-like activities in the brain during development, regeneration, and tumorigenesis (6-10). Indeed, considerable data indicate that PACAP, mainly via PAC1, regulates neural cell proliferation, survival, axon regeneration and oligodendrocyte progenitor proliferation and maturation (6-9, 11-13).A series of studies beginning in the early 1980s implicated VIP as a regulator of immune function (14). These studies revealed that VIP can modulate both innate and adaptive immunity, showing a predominant anti-inflammatory action on macrophages, promoting a positive Th2/Th1 cytokine balance, and enhancing the production of regulatory T cells (Tregs) (15). Later it was found that PACAP could mimic many of these actions, suggesting the involvement of VPAC receptors. Moreover, it was determined that both VIP and PACAP are expressed in lymphocytes and other immune cell types (16-18), indicating that modulation of inflammation could result from either neurogenic or immunogenic neuropeptide expression. Finally, in the last decade, an increasing body of in vivo data indicates that VPAC receptors may be promising targets for the treatment of inflammatory diseases, and in particular, Th1-associated pathologies such as MS and rheumatoid arthritis. Indeed, adminis...

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“…PACAP is thought to be an important sensory neuropeptide, which was described in the superficial spinal horn layers and in neurons of the dorsal root ganglia (17,22) and can play a role in conduction of sensory stimuli in pain reactions during various pathological processes (15). On the other hand, it is well known that IBD may lead to severe and longlasting pain (3,27).…”

Section: Discussionmentioning

confidence: 99%

Pituitary adenylate cyclase activating peptide-27 – like immunoreactive nerve fibers in the mucosal layer of canine gastrointestinal tract in physiology and during inflammatory bowel disease

Gonkowski

Rychlik

Całka

2013

Bulletin of the Veterinary Institute in Pulawy

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Changes in the density of mucosal pituitary adenylate cyclase activating peptide-27 -like immunoreactive (PACAP-27 -LI) nerve fibers within various parts of the canine gastrointestinal (GI) tract during inflammatory bowel disease (IBD) were investigated. The distribution of nerves were studied, using a single-labelling immunofluorescence technique, in the mucosal layer of canine stomach, duodenum, jejunum, and descending colon. Canine IBD caused an increase in the density of PACAP-27-LI mucosal nerves in all studied parts of GI tract. The results suggest that PACAP in the nervous system may be involved in pathological processes during IBD.

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Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide

Cited by 104 publications

References 43 publications

Glucose‐dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion‐affected expression, and impaired regenerative axonal growth

Glucose‐dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion‐affected expression, and impaired regenerative axonal growth

Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis

Pituitary adenylate cyclase activating peptide-27 – like immunoreactive nerve fibers in the mucosal layer of canine gastrointestinal tract in physiology and during inflammatory bowel disease

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