Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice
Kengo Suzuki,Yoshiaki Ohi,Toyohiro Sato,Yoshitaka Tsuda,Yuta Madokoro,Masayuki Mizuno,Kenichi Adachi,Yuto Uchida,Akira Haji,Kosei Ojika,Noriyuki Matsukawa +10 more
TLDR
In this paper , the importance of hippocampal cholinergic neuro-stimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus was investigated.Abstract:
Abstract Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer’s disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus. Here, we demonstrate that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic function via a decrease in vesicular acetylcholine transporter in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. The results, in combination with our previous reports that show the reduction of hippocampal theta power through a decrease of a region-specific choline acetyltransferase in the stratum oriens of CA1 and the decrease of acetylcholine concentration in the hippocampus, may indicate the defined cholinergic dysfunction in HCNP-pp KO mice. This may also support that HCNP-pp KO mice are appropriate genetic models for cholinergic functional impairment in septo-hippocampal interactions. Therefore, according to the cholinergic hypothesis, the model mice might are potential partial pathological animal models for Alzheimer’s disease. read more
Citations
More filters
Journal ArticleDOI
Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus
Yuta Madokoro,Daisuke Kato,Yoshitaka Tsuda,Itsumi Arakawa,Kengo Suzuki,Toyohiro Sato,Masayuki Mizuno,Yuto Uchida,Kosei Ojika,Noriyuki Matsukawa +9 more
TL;DR: In this article , the authors investigated whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholineergic dysfunction of HCNP-pp conditional knockout (cKO).
References
More filters
Journal ArticleDOI
Selective loss of central cholinergic neurons in alzheimer's disease
Peter Davies,A.J.F. Maloney +1 more
Journal ArticleDOI
Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6).
TL;DR: It appears that the age-related changes of memory function as well as some of the behavioral disturbances seen in the dementia of Alzheimer's Disease may be related to pathological alterations along central cholinergic pathways.
Journal ArticleDOI
The three-dimensional organization of the hippocampal formation: a review of anatomical data.
David G. Amaral,Menno P. Witter +1 more
TL;DR: It is concluded that it is heuristically most reasonable to consider the hippocampal formation as a three-dimensional cortical region with important information processing taking place in both the transverse and long axes.
Journal ArticleDOI
The cholinergic system in aging and neuronal degeneration.
Reinhard Schliebs,Thomas Arendt +1 more
TL;DR: Observed changes in the expression of NGF, its precursor proNGF, the high and low NGF receptors, trkA and p75NTR, respectively, changes in acetylcholine release, high-affinity choline uptake, as well as alterations in muscarinic and nicotinic acetyl choline receptor expression may contribute to the cholinergic dysfunction.
Journal ArticleDOI
Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP
Kam C. Yeung,T Seitz,Shengfeng Li,Petra Janosch,Brian McFerran,Christian M. Kaiser,Frances Fee,Kostas D. Katsanakis,David W. Rose,Harald Mischak,John M. Sedivy,Walter Kolch +11 more
TL;DR: RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module and competitively disrupts the interaction between these kinases.