22 research outputs found
Evaluation of alpha-synuclein immunohistochemical methods for the detection of Lewy-type synucleinopathy in gastrointestinal biopsies
Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease
Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.Clinicaltrials.gov NCT01155492
Classical Parkinson disease versus Parkinson complex ? Reflections against staging and in favour of heterogeneity
Skin biopsies in myelin-related neuropathies: bringing molecular pathology to the bedside
Skin biopsy is a minimally invasive procedure and has
been used in the evaluation of non-myelinated, but not
myelinated nerve fibres, in sensory neuropathies. We
therefore evaluated myelinated nerves in skin biopsies
from normal controls and patients with Charcot\u2013
Marie\u2013Tooth (CMT) disease caused by mutations in
myelin proteins. Light microscopy, electron microscopy
and immunohistochemistry routinely identified myelinated
dermal nerves in glabrous skin that appeared similar
to myelinated fibres in sural and sciatic nerve. Myelin
abnormalities were observed in all patients with CMT.
Moreover, skin biopsies detected potential pathogenic
abnormalities in the axolemmal molecular architecture
previously undetected in human neuropathies. Finally,
myelin gene expression at both mRNA and protein levels
was evaluated by real-time PCR and immunoelectron
microscopy. Peripheral myelin protein 22 (PMP22) was
increased in CMT1A (PMP22 duplication) and decreased
in patients with hereditary neuropathy with liability to
pressure palsies (PMP22 deletion). Taken together, our
data suggest that skin biopsy may in certain circumstances
replace the more invasive sural nerve biopsy in
the morphological and molecular evaluation of inherited
and other demyelinating neuropathies
Parkinson's Disease: Distribution of Lewy Bodies in the Peripheral Autonomic Nervous System
Long-Term Control of Recurrent Anaplastic Ependymoma With Extracranial Metastasis: Importance of Multiple Surgery and Stereotactic Radiosurgery Procedures-Case Report-
Pontine Glioblastoma Multiforme Initially Presenting With Leptomeningeal Gliomatosis. Case Report.
Organization and chemical neuroanatomy of the African elephant (Loxodonta africana) hippocampus
Elephants are thought to possess excellent long-term spatial–temporal and social memory, both memory types being at least in part hippocampus dependent. Although the hippocampus has been extensively studied in common laboratory mammalian species and humans, much less is known about comparative hippocampal neuroanatomy, and specifically that of the elephant. Moreover, the data available regarding hippocampal size of the elephant are inconsistent. The aim of the current study was to re-examine hippocampal size and provide a detailed neuroanatomical description of the hippocampus in the African elephant. In order to examine the hippocampal size the perfusion-fixed brains of three wild-caught adult male African elephants, aged 20–30 years, underwent MRI scanning. For the neuroanatomical description brain sections containing the hippocampus were stained for Nissl, myelin, calbindin, calretinin, parvalbumin and doublecortin. This study demonstrates that the elephant hippocampus is not unduly enlarged, nor specifically unusual in its internal morphology. The elephant hippocampus has a volume of 10.84 ± 0.33 cm³ and is slightly larger than the human hippocampus (10.23 cm3). Histological analysis revealed the typical trilaminated architecture of the dentate gyrus (DG) and the cornu ammonis (CA), although the molecular layer of the dentate gyrus appears to have supernumerary sublaminae compared to other mammals. The three main architectonic fields of the cornu ammonis (CA1, CA2, and CA3) could be clearly distinguished. Doublecortin immunostaining revealed the presence of adult neurogenesis in the elephant hippocampus. Thus, the elephant exhibits, for the most part, what might be considered a typically mammalian hippocampus in terms of both size and architectur