Enhanced hippocampal acetylcholine release in nociceptin-receptor knockout mice

Uezu, Kayoko; Sano, Atsuko; Séi, Hiroyoshi; Toida, Kazunori; Houtani, Takeshi; Sugimoto, Tetsuo; Suzuki-Yamamoto, Toshiko; Takeshima, Hiroshi; Ishimura, Kazunori; Morita, Yusuke

doi:10.1016/j.brainres.2005.05.044

Cited by 20 publications

(16 citation statements)

References 29 publications

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“…The positive interaction between Ro64-6198 and MK-801 is in agreement with the notion that NOP and NMDA receptors modulate mnemonic function through common neural targets (Goeldner et al, 2008(Goeldner et al, , 2009Mamiya et al, 2003). The absence of a positive interaction obtained with Ro64-6198 and the cholinergic antagonists was unexpected given the neurochemical evidence suggesting the existence of negative functional interaction between N/OFQ and central cholinergic systems (Cavallini et al, 2003;Uezu et al, 2005). It is unlikely that drug doses used were not optimal for revealing a positive interaction.…”

Section: Ro64-6198/mk-801supporting

confidence: 76%

“…I.e. N/OFQ reduces cholinergic transmission in many brain structures, including the hippocampus (Cavallini, Marino, Beani, Bianchi, & Siniscalchi, 2003;Itoh, Konya, Takai, Masuda, & Nagai, 1999), while deletion of NOP receptor gene enhances basal hippocampal acetylcholine levels (Uezu et al, 2005). In the present study, we used the novel object exploration task to explore for the first time the contribution of cholinergic component to the inhibitory influence of NOP receptors on recognition memory.…”

Section: Introductionmentioning

confidence: 96%

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The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs recognition memory formation through interaction with glutamatergic but not cholinergic receptor antagonists

Reiss

Prinssen

Wichmann

et al. 2012

Neurobiology of Learning and Memory

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Section: Ro64-6198/mk-801supporting

confidence: 76%

Section: Introductionmentioning

confidence: 96%

The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs recognition memory formation through interaction with glutamatergic but not cholinergic receptor antagonists

Reiss

Prinssen

Wichmann

et al. 2012

Neurobiology of Learning and Memory

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“…They also provide the first evidence that NOP and NMDA receptors converge on common ERK pathway in the hippocampus to regulate memory formation. However, it cannot be excluded that the amnesic effects of Ro64-6198 might also involve a cholinergic component (Cavallini et al, 2003;Uezu et al, 2005) that is known to contribute to recognition memory formation (Dodart et al, 1997;Bertaina-Anglade et al, 2006) and to activate ERK cascade in neurons (Rosenblum et al, 2000;Giovannini, 2006;Steiner et al, 2007) Functional interaction between NOP and NMDA receptors may involve both presynaptic and postsynaptic mechanisms. For instance, this could occur at the level of neuronal circuitry, as N/OFQ was shown to suppress synaptic transmission in many brain regions, including the hippocampus, through presynaptic inhibition of neurotransmitters release (Meis, 2003).…”

Section: Discussionmentioning

confidence: 99%

Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus

Goeldner¹,

Reiss²,

Wichmann³

et al. 2008

J. Neurosci.

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-801), given systemically, also suppressed ERK activation and disrupted recognition memory. In contrast, no effect of MK-801 was observed on recall, as for Ro64-6198. When administered concurrently at subthreshold doses, Ro64-6198 and MK-801 synergistically suppressed hippocampal ERK activation and impaired long-term memory formation. Under resting conditions, neither Ro64-6198 nor MK-801 affected spontaneous ERK activity in the hippocampus at the amnesic doses whereas at higher doses, only MK-801 had a suppressive effect. We conclude that N/OFQ-NOP receptor system negatively regulates long-term recognition memory formation through hippocampal ERK signaling mechanisms. This modulation may in part take place by inhibiting glutamatergic function at the NMDA receptor.

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“…After baseline assessment, novel objects were introduced into the experimental chamber. Novel object introduction (NOI) has been previously shown to stimulate ACh release (28), which was used here to differentiate the responses between the APPsw control and the double mice. For treatments, the perfusion fluid was switched to artificial cerebrospinal fluid containing methoctramine tetrahydrochloride or eserine (both drugs were obtained from Sigma) through the UniSwitch liquid switch syringe selector (IBL-America).…”

Section: Methodsmentioning

confidence: 99%

GRK5 Deficiency Accelerates β-Amyloid Accumulation in Tg2576 Mice via Impaired Cholinergic Activity

Cheng

He²,

Liu

et al. 2010

Journal of Biological Chemistry

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Membrane G protein-coupled receptor kinase 5 (GRK5) deficiency is linked to Alzheimer disease, yet its precise roles in the disease pathogenesis remain to be delineated. We have previously demonstrated that GRK5 deficiency selectively impairs desensitization of presynaptic M2 autoreceptors, which causes presynaptic M2 hyperactivity and inhibits acetylcholine release. Here we report that inactivation of one copy of Grk5 gene in transgenic mice overexpressing ␤-amyloid precursor protein (APP) carrying Swedish mutations (Tg2576 or APPsw) resulted in significantly increased ␤-amyloid (A␤) accumulation, including increased A␤ ؉ plaque burdens and soluble A␤ in brain lysates and interstitial fluid (ISF). In addition, secreted ␤-APP fragment (sAPP␤) also increased, whereas fulllength APP level did not change, suggesting an alteration in favor of ␤-amyloidogenic APP processing in these animals. Reversely, perfusion of methoctramine, a selective M2 antagonist, fully corrected the difference between the control and GRK5-deficient APPsw mice for ISF A␤. In contrast, a cholinesterase inhibitor, eserine, although significantly decreasing the ISF A␤ in both control and GRK5-deficient APPsw mice, failed to correct the difference between them. However, combining eserine with methoctramine additively reduced the ISF A␤ further in both animals. Altogether, these findings indicate that GRK5 deficiency accelerates ␤-amyloidogenic APP processing and A␤ accumulation in APPsw mice via impaired cholinergic activity and that presynaptic M2 hyperactivity is the specific target for eliminating the pathologic impact of GRK5 deficiency. Moreover, a combination of an M2 antagonist and a cholinesterase inhibitor may reach the maximal disease-modifying effect for both amyloid pathology and cholinergic dysfunction.Alzheimer disease (AD 3 ) is a devastating neurodegenerative disorder clinically characterized by progressive loss of memory and other neurological functions. Given that basal forebrain cholinergic neurons are the fundamental basis for memory function, any of the pathological causes in AD, no matter whether they are the hallmark changes of ␤-amyloid (A␤)-enriched senile plaques and neurofibrillary tangles or of the prominent inflammation, have to eventually converge to the extensive basal forebrain cholinergic neuronal loss in AD.Mounting evidence suggests that the excessive accumulation of A␤ is a paramount pathological event leading to AD, either by direct neuronal toxicity or by indirect exacerbation of inflammatory damage to neurons (1, 2). The amyloid precursor protein (APP) can be proteolytically processed either through the ␤-amyloidogenic pathway by ␤-and ␥-secretases or via the non-␤-amyloidogenic pathway by ␣-secretase. The regulation of these two mutually exclusive pathways determines the amount of A␤ production and is thus critically important for the pathogenesis of AD. Previous studies have demonstrated that proteolytic APP processing can be regulated by a variety of G protein-coupled receptors, including cholinergic, se...

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Enhanced hippocampal acetylcholine release in nociceptin-receptor knockout mice

Cited by 20 publications

References 29 publications

The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs recognition memory formation through interaction with glutamatergic but not cholinergic receptor antagonists

The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs recognition memory formation through interaction with glutamatergic but not cholinergic receptor antagonists

Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus

GRK5 Deficiency Accelerates β-Amyloid Accumulation in Tg2576 Mice via Impaired Cholinergic Activity

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