| 1. |
- Schmid, Eduard, et al.
(författare)
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Neurokinin A is a main constituent of sensory neurons innervating the anterior segment of the eye
- 2005
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 46:1, s. 268-274
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To study the innervation pattern of the anterior segment of the eye by neurokinin (NK)-A-immunoreactive nerves and to determine their sensory origin. METHODS. The presence and distribution of NKA was examined in human eyes by radioimmunoassay and immunofluorescence. The source of nerves was determined by measuring the concentration of NKA in the trigeminal ganglion (TG) in comparison with that of the classic sensory peptides substance P (SP) and calcitonin gene-related peptide (CGRP) and in eye tissues in capsaicin-pretreated rats versus control subjects. The NKA-like immunoreactivities were further characterized by reversed phase HPLC in the rat TG and the human iris- ciliary body complex. The presence of γ-PPT-A mRNA was studied in the rat TG by in situ hybridization. RESULTS. The levels of NKA in human eye tissues were approximately 10 times higher than those of SP but lower than those of CGRP. Nerve fibers were visualized in the cornea, the trabecular meshwork, the iridial stroma, and, prominently, in the sphincter muscle, the ciliary body stroma and muscle and processes, and the choroidal stroma and surrounding blood vessels. In the rat TG, the concentration of NKA was approximately five times higher than that of SP. Capsaicin led to a >60% decrease of the concentration of the peptide in the rat TG and rat eye tissues except for the retina. NKA-like immunoreactivities were present in a single peak corresponding to synthetic NKA, both in the rat TG and in the human iris- ciliary body complex, and numerous ganglion cells of small size were labeled by a γ-PPT-A probe in the rat TG. CONCLUSIONS. The present results clearly demonstrate that NKA is a main constituent of sensory neurons innervating the anterior segment of the eye. The presence of the peptide in C fibers in ocular tissues indicates a participation in sensory transmission and an involvement in the irritative response in the eye, a model for neurogenic inflammation in lower mammals.
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| 2. |
- Hohsfield, Lindsay A., et al.
(författare)
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Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer's disease mouse models
- 2014
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Ingår i: Molecular and cellular neuroscience. - : Academic Press. - 1044-7431. ; 63, s. 83-95
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown that elevated plasma cholesterol levels (i.e. hypercholesterolemia) serve as a risk factor for late-onset Alzheimer's disease (AD). However, it remains unclear how hypercholesterolemia may contribute to the onset and progression of AD pathology. In order to determine the role of hypercholesterolemia at various stages of AD, we evaluated the effects of high cholesterol diet (5% cholesterol) in wild-type (WT; C57BL6) and triple-transgenic AD (3xTg-AD: Psen1, APPSwe, tauB301L) mice at 7, 14, and 20 months. The transgenic APP-Swedish/Dutch/Iowa AD mouse model (APPSwDI) was used as a control since these animals are more pathologically-accelerated and are known to exhibit extensive plaque deposition and cerebral amyloid angiopathy. Here, we describe the effects of high cholesterol diet on: (1) cognitive function and stress, (2) AD-associated pathologies, (3) neuroinflammation, (4) blood-brain barrier disruption and ventricle size, and (5) vascular dysfunction. Our data show that high dietary cholesterol increases weight, slightly impairs cognitive function, promotes glial cell activation and complement-related pathways, enhances the infiltration of blood-derived proteins and alters vascular integrity, however, it does not induce AD-related pathologies. While normal-fed 3xTg-AD mice display a typical AD-like pathology in addition to severe cognitive impairment and neuroinflammation at 20 months of age, vascular alterations are less pronounced. No microbleedings were seen by MRI, however, the ventricle size was enlarged. Triple-transgenic AD mice, on the other hand, fed a high cholesterol diet do not survive past 14 months of age. Our data indicates that cholesterol does not markedly potentiate AD-related pathology, nor does it cause significant impairments in cognition. However, it appears that high cholesterol diet markedly increases stress-related plasma corticosterone levels as well as some vessel pathologies. Together, our findings represent the first demonstration of prolonged high cholesterol diet and the examination of its effects at various stages of cerebrovascular- and AD-related disease.
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| 3. |
- Mattsson, Niklas, 1979, et al.
(författare)
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The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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| 4. |
- Willis, Michael, et al.
(författare)
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Chromogranin B and Secretogranin II in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in Alzheimer patients
- 2008
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 13:2, s. 123-135
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Tidskriftsartikel (refereegranskat)abstract
- Chromogranin B and secretogranin II are major soluble constituents of large dense core vesicles of presynaptic structures and have been found in neuritic plaques of Alzheimer patients. We examined the distribution and expression of these peptides in both transgenic mice over expressing human amyloid-beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem brain. In transgenic mice, the number of amyloid-beta plaques and chromogranin immunopositive plaques increased from 6 to 12 months. About 60% of amyloid-beta plaques were associated with chromogranin B and about 40% with secretogranin II. Chromogranin immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fibrillary acidic protein- immunoreactivity was expressed in chromogranin immunoreactive structures at any timepoint. Density of chromogranin peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resembled findings in Alzheimer patients. Chromogranin peptides were associated with amyloid-beta plaques, but were not reduced in specific brain areas as previously reported by our group. Therefore specific changes of chromogranin peptides observed in Alzheimer patients can be related to amyloid-beta pathology only.
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