title: Loss of nitrergic and cholinergic neurons in the enteric nervous system of APP/PS1 transgenic mouse model.
abstract: Alzheimer's disease (AD) is an age-related neurodegenerative brain disorder characterized by aggregation of amyloid-β (Aβ) peptide, formation of neurofibrillary tangles, synaptic loss, and neuronal cell death; however, the characteristic pathological alterations taking place in the "second brain"-enteric nervous system is still largely undefined. In this study, we aimed to detect the pathological changes in the APP/PS1 mice ileum by a novel whole mount technique. The deposition of Aβ plaque and the overexpression of phosphorylated Tau (pTau) protein were observed in the myenteric neurons of APP/PS1 mice. Compared to the control mice, the proportions of neuronal nitric oxide synthase (nNOS)+and choline acetyltransferase (ChAT)+neurons in the myenteric plexus of APP/PS1 mice significantly decreased (p<0.05). Moreover, whole mount preparations and paraffin sections both demonstrated that the number of CD68+ macrophages in the APP/PS1 mice ileum significantly increased (p<0.05). But, there was no significant difference (p>0.05) in the number of enteric HuC/D+ neurons and the density of Tuj1 between the APP/PS1 and wild type mice, which may be due to the compensatory function of enteric nervous system. These results suggest that the deposition of Aβ plaque and pTau might activate the enteric resident macrophages, further leading to the loss of myenteric nitrergic and cholinergic neurons in the enteric nervous system.
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China. Electronic address: wang-yongxiang@hotmail.com.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China. Electronic address: duyifeng2013@163.com.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Du
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D026602:Nitrergic Neurons / Q000378:metabolism / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1
keywords: Alzheimer’s disease; Cholinergic neuron; Enteric nervous system; Nitrergic neuron