Prokineticin 2 modulates the excitability of area postrema neurons in vitro in the rat

Ingves, Matthew V.; Ferguson, Alastair V.

doi:10.1152/ajpregu.00620.2009

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…Certainly, the possible effects of PROK2 dysregulation at the synaptic level remain largely unexplored and might involve complex mechanisms. For example, previous electrophysiological experiments have demonstrated that PROK2 might reduce the GABAergic function 52 53 or modulate voltage-gated ion channels 54 , the balance of which finely regulates intrinsic excitability and synaptic plasticity events. Thus, application of PC1 might rescue LTP impairment in the Tg2576 model by preserving synaptic homeostasis and vulnerability to the PROK2 insult.…”

Section: Discussionmentioning

confidence: 99%

Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

Severini

Lattanzi²,

Maftei³

et al. 2015

Sci Rep

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Bv8/Prokineticin 2 (PROK2) is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Among multiple biological roles demonstrated for PROK2, it was recently established that PROK2 is an insult-inducible endangering mediator for cerebral damage. Aim of the present study was to evaluate the PROK2 and its receptors’ potential involvement in amyloid beta (Aβ) neurotoxicity, a hallmark of Alzheimer’s disease (AD) and various forms of traumatic brain injury (TBI). Analyzing primary cortical cultures (CNs) and cortex and hippocampus from Aβ treated rats, we found that PROK2 and its receptors PKR1 and PKR2 mRNA are up-regulated by Aβ, suggesting their potential involvement in AD. Hence we evaluated if impairing the prokineticin system activation might have protective effect against neuronal death induced by Aβ. We found that a PKR antagonist concentration-dependently protects CNs against Aβ1–42-induced neurotoxicity, by reducing the Aβ-induced PROK2 neuronal up-regulation. Moreover, the antagonist completely rescued LTP impairment in hippocampal slices from 6 month-old Tg2576 AD mice without affecting basal synaptic transmission and paired pulse-facilitation paradigms. These results indicate that PROK2 plays a role in cerebral amyloidosis and that PROK2 antagonists may represent a new approach for ameliorating the defining pathology of AD.

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Section: Discussionmentioning

confidence: 99%

Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

Severini

Lattanzi²,

Maftei³

et al. 2015

Sci Rep

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“…The smaller peak of PK2 may contribute to potentiating glutamate excitotoxicity, because PK2 is neuro-excitatory (21)(22)(23). The larger PK2 expression at 24 h may have an additional role; this time point also marks the period when upregulation of a number of proinflammatory genes and infiltration of various inflammatory cells, such as monocytes and macrophages, occurs poststroke (3,48).…”

Section: Discussionmentioning

confidence: 99%

“…Since their initial discovery in 2001, multiple physiological roles for PKs have been discovered, including gastrointestinal motility (12), generation of circadian rhythms (14)(15)(16), angiogenesis (17,18) and choroidal neovascularization (19), olfactory bulb neurogenesis (20), neuroexcitation (21)(22)(23)(24), inflammation (25)(26)(27)(28), and reproduction (29,30). Recent evidence implicated PK2 in a human disease in which different point mutations in genes encoding PK2 or its receptor (PKR2) lead to a type of Kallmann syndrome (29), a disease characterized by abnormal olfactory function and underdeveloped gonads caused by a deficiency in hypothalamic gonadotropin-releasing hormones.…”

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confidence: 99%

Prokineticin 2 is an endangering mediator of cerebral ischemic injury

Cheng¹,

Lee

Culbertson³

et al. 2012

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

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Stroke causes brain dysfunction and neuron death, and the lack of effective therapies heightens the need for new therapeutic targets. Here we identify prokineticin 2 (PK2) as a mediator for cerebral ischemic injury. PK2 is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Multiple biological roles for PK2 have been discovered, including circadian rhythms, angiogenesis, and neurogenesis. However, the role of PK2 in neuropathology is unknown. Using primary cortical cultures, we found that PK2 mRNA is up-regulated by several pathological stressors, including hypoxia, reactive oxygen species, and excitotoxic glutamate. Glutamate-induced PK2 expression is dependent on NMDA receptor activation and extracellular calcium. Enriched neuronal culture studies revealed that neurons are the principal source of glutamate-induced PK2. Using in vivo models of stroke, we found that PK2 mRNA is induced in the ischemic cortex and striatum. Central delivery of PK2 worsens infarct volume, whereas PK2 receptor antagonist decreases infarct volume and central inflammation while improving functional outcome. Direct central inhibition of PK2 using RNAi also reduces infarct volume. These findings indicate that PK2 can be activated by pathological stimuli such as hypoxia-ischemia and excitotoxic glutamate and identify PK2 as a deleterious mediator for cerebral ischemia.excitotoxicity | RNA interference | Akt | Erk1,2 | SAP/JNK

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“…PK2 has been shown to modulate the electrical activity of neurons through the activation of PKR2 in the area postrema, subfornical organ, and paraventricular nucleus of the hypothalamus [26]–[28]. Interestingly, PKR2 mRNA is also expressed in the SCN [17], [21], and PKR2 mRNA-containing neurons are clustered in the dorsomedial region of the SCN [20], suggesting that these receptors may play a crucial role in regulating neuronal activity of the SCN.…”

Section: Introductionmentioning

confidence: 99%

Prokineticin 2 Regulates the Electrical Activity of Rat Suprachiasmatic Nuclei Neurons

et al. 2011

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Neuropeptide signaling plays roles in coordinating cellular activities and maintaining robust oscillations within the mammalian suprachiasmatic nucleus (SCN). Prokineticin2 (PK2) is a signaling molecule from the SCN and involves in the generation of circadian locomotor activity. Prokineticin receptor 2 (PKR2), a receptor for PK2, has been shown to be expressed in the SCN. However, very little is known about the cellular action of PK2 within the SCN. In the present study, we investigated the effect of PK2 on spontaneous firing and miniature inhibitory postsynaptic currents (mIPSCs) using whole cell patch-clamp recording in the SCN slices. PK2 dose-dependently increased spontaneous firing rates in most neurons from the dorsal SCN. PK2 acted postsynaptically to reduce γ-aminobutyric acid (GABA)-ergic function within the SCN, and PK2 reduced the amplitude but not frequency of mIPSCs. Furthermore, PK2 also suppressed exogenous GABA-induced currents. And the inhibitory effect of PK2 required PKC activation in the postsynaptic cells. Our data suggest that PK2 could alter cellular activities within the SCN and may influence behavioral and physiological rhythms.

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Prokineticin 2 modulates the excitability of area postrema neurons in vitro in the rat

Cited by 10 publications

References 51 publications

Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

Prokineticin 2 is an endangering mediator of cerebral ischemic injury

Prokineticin 2 Regulates the Electrical Activity of Rat Suprachiasmatic Nuclei Neurons

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