]When I was working it was a joke that I was always making obscure links .Is this of interest to P.D community or is it just another obscure link.?

Virus may affect memory decades later, study finds


Reuters Health

Monday, October 23, 2006


WASHINGTON (Reuters) - Forget where you left your glasses? Did those keys go missing again? Now you do not have to blame your spouse -- a virus may be to blame.

A family of viruses that cause a range of ills from the common cold to polio may be able to infect the brain and cause steady damage, a team at the Mayo Clinic in Minnesota reported on Monday.

"Our study suggests that virus-induced memory loss could accumulate over the lifetime of an individual and eventually lead to clinical cognitive memory deficits," said Charles Howe, who reported the findings in the journal Neurobiology of Disease.

The viruses are called picornaviruses and infect more than 1 billion people worldwide each year. They include the virus that causes polio, as well as colds and diarrhea. People contract two or three such infections a year on average.

"We think picornavirus family members cross into the brain and cause a variety of brain injuries. For example, the polio virus can cause paralysis," Howe said.

"It can injure the spinal cord and different parts of the brain responsible for motor function. In the murine (mouse) virus we studied, it did the same thing and also injured parts of the brain responsible for memory."

The Mayo Clinic infected mice with a virus called Theiler's murine encephalomyelitis virus, which is similar to human poliovirus.

Infected mice later had difficulty learning to navigate a maze. Some were barely affected, while others were completely unable to manage, and when the mice were killed and their brains examined, a correlating amount of damage was seen in the hippocampus region, related to learning and memory.

One virus particularly likely to cause brain damage is enterovirus 71, which is common in Asia, the researchers said. It can cross over into the brain and cause encephalitis, a brain inflammation that can lead to coma and death.

"Our findings suggest that picornavirus infections throughout the lifetime of an individual may chip away at the cognitive reserve, increasing the likelihood of detectable cognitive impairment as the individual ages," the researchers wrote in their report.

"We hypothesize that mild memory and cognitive impairments of unknown etiology may, in fact, be due to accumulative loss of hippocampus function caused by repeated infection with common and widespread neurovirulent picornaviruses."

Other viruses are known to kill brain cells, including the herpes virus and human immunodeficiency virus or HIV

We should all start meditating consistantly and grow our brains:

Meditation Associated With Increased Grey Matter In The Brain

Meditation is known to alter resting brain patterns, suggesting long lasting brain changes, but a new study by researchers from Yale, Harvard, Massachusetts General Hospital, and the Massachusetts Institute of Technology shows meditation also is associated with increased cortical thickness.


The structural changes were found in areas of the brain that are important for sensory, cognitive and emotional processing, the researchers report in the November issue of NeuroReport.

Although the study included only 20 participants, all with extensive training in Buddhist Insight meditation, the results are significant, said Jeremy Gray, assistant professor of psychology at Yale and co-author of the study led by Sara Lazar, assistant in psychology at Massachusetts General Hospital.

"What is most fascinating to me is the suggestion that meditation practice can change anyone's grey matter," Gray said. "The study participants were people with jobs and families. They just meditated on average 40 minutes each day, you don't have to be a monk."

Magnetic resonance imaging showed that regular practice of meditation is associated with increased thickness in a subset of cortical regions related to sensory, auditory, visual and internal perception, such as heart rate or breathing. The researchers also found that regular meditation practice may slow age-related thinning of the frontal cortex.

"Most of the regions identified in this study were found in the right hemisphere," the researchers said. "The right hemisphere is essential for sustaining attention, which is a central practice of Insight meditation."

They said other forms of yoga and meditation likely have a similar impact on cortical structure, although each tradition would be expected to have a slightly different pattern of cortical thickening based on the specific mental exercises involved.
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Co-authors include Catherine Kerr, Rachel Wasserman Jeffery Dusek, Herbert Benson and Metta McGarvey, Harvard; Douglas Greve, Brian Quinn, Bruce Fischl, Michael Treadway and Scott Rauch, Massachusetts General Hospital, and Christopher Moore, Massachusetts Institute of Technology.

NeuroReport 16: 1893-1897 (November 28, 2005)

One of the hallmarks of PD is the clumps in neurons called Lewy bodies. These are glycation products formed when sugars and proteins interact. They belong to a family of similar (maybe even identical) clumps with other names, usually that of the guy who first described them.

Lewy was the guy that described them in PD, thus the name. The ONLY thing that definitively says that you had PD is if there are Lewy bodies in your SN once you are dead. That's the "gold standard." So lewy bodies are important.

Anne Frobert, who occasionally posts here, turned me on to the work of a researcher named Braak. He discovered that Lewy bodies are, indeed, found in the SN but he also discovered that they showed up there last. First, they showed up in the wall of the stomach. Then they followed a path up the vagal nerve to the brainstem and through the brain centers one by one and finally to the SN.

Think of the lewy bodies as footprints on the beach. The first one represents the stomach and the others form a string through both time and space toward the SN. But the first footprint is the one before you.

PD doesn't start in the SN. It doesn't even begin in the brain. It starts in the stomach wall and creeps up the nerve pathways and eventually ends up in the SN.

It could be a virus, a bacterium, or a toxin. Or a combination.

We know that a virus can live in the nerve fibers and follow them to cause shingles, for example. We know that several viruses cause clumps similar to Lewy bodies, too.

Yes, I think this story is very interesting.

That's interesting, Rick!

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
Journal Journal of Neural Transmission
Publisher Springer Wien
ISSN 0300-9564 (Print) 1435-1463 (Online)
Subject Biomedical and Life Sciences and Medicine
Issue Volume 110, Number 5 / May, 2003
DOI 10.1007/s00702-002-0808-2
Pages 517-536
Online Date Thursday, February 19, 2004

Authors
H. Braak, U. Rüb, W. P. Gai, K. Del Tredici
Abstract

Summary. The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex.


With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve.


This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve.

By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.


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Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of idiopathic parkinsonism

http://www.blackwell-synergy.com/doi...im.2005.01.011

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: Neurosci Lett. 2006 Jun 19;401(1-2):146-9. Epub 2006 Apr 4.

Intragastric proteasome inhibition induces alpha-synuclein-immunopositive aggregations in neurons in the dorsal motor nucleus of the vagus in rats.

Miwa H, Kubo T, Suzuki A, Kondo T.

Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-8510, Japan. h-miwa@wakayama-med.ac.jp

The neuropathological hallmark of idiopathic Parkinson's disease (PD) is dopaminergic neuron degeneration in the substantia nigra. However, it has been suggested that the neurodegenerative process initially may occur in the dorsal motor nucleus of the vagus (DMV). This implies that unidentified environmental toxins or neurotropic pathogens that is capable of passing the mucosal barrier of the gastrointestinal tract might affect the enteric nerve endings of the vagal neurons, possibly resulting in retrograde degeneration of the DMV.

The present study aimed to evaluate the effects of proteasome inhibition of the intragastric nerve terminals of the DMV in rats. Following multiple injections of PSI, a selective proteasome inhibitor, or vehicle into the ventral wall of the stomach, the medulla oblongata was studied immunohistologically. In the DMV neurons of rats treated with PSI but not vehicle, alpha-synuclein-immunopositive intracytoplasmic inclusions and activated microglia were observed, predominantly in the left DMV. However, there was no significant loss of neurons.

These results suggest that intragastric proteasome inhibition has a retrograde effect on DMV neurons but is insufficient to induce cell death, suggesting no causal linkage between inclusion body formation with proteasome inhibition and neuron death in the DMV. This might also implicate that Lewy body formation in the DMV in PD is possibly related to peroral invasion of environmental toxins that inhibit ubiquitin-proteasome system function.

full article:

http://www.sciencedirect.com/science...d0e93e428aca90

Neuropathology & Applied Neurobiology
Volume 32 Page 284 - June 2006
doi:10.1111/j.1365-2990.2006.00727.x
Volume 32 Issue 3


A. Bloch, A. Probst, H. Bissig, H. Adams and M. Tolnay
A. Bloch, A. Probst, H. Bissig, H. Adams and M. Tolnay (2006) Neuropathology and Applied Neurobiology 32, 284–295

α-Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects

Studies on cases with incidental Lewy body disease (ILBD) suggest that α-synuclein (αSN) pathology of Parkinson's disease (PD) starts in lower brainstem nuclei and in the olfactory bulb. However, medullary structures as the induction site of αSN pathology have been questioned as large parts of the nervous system, including the spinal cord and the peripheral autonomic nervous system (PANS), have not been examined in ILBD. Thus, the time course of PD lesions in the spinal cord or PANS in relation to medullary lesions remains unknown.

We collected 98 post mortem cases with no reference to PD-associated symptoms on clinical records. αSN pathology was found in the central nervous system, including the spinal cord, and in the PANS in 17 (17.3%) cases. αSN pathology was encountered in autonomic nuclei of the thoracic spinal cord, brainstem and olfactory nerves in 17/17, in sacral parasympathetic nuclei in 15/16, in the myenteric plexus of oesophagus in 14/17, in sympathetic ganglia in 14/17, and in the vagus nerve in 12/16 cases. In addition to the thoracic lateral horns, a high number of αSN lesions was also found in non-autonomic spinal cord nuclei.

Considering supraspinal structures our cases corresponded roughly to the recently described sequential order of αSN involvement in PD. Our study indicates, however, that the autonomic nuclei of the spinal cord and the PANS belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves. A larger cohort of ILBD cases will be needed to pinpoint the precise induction site of αSN pathology among these structures.
http://www.blackwell-synergy.com/doi...0.2006.00727.x

I can send you the full article if you want it.

Discussion in that article:



In this study, we sought to determine how often and where αSN pathology occurs in neurologically unimpaired elderly individuals. We were especially interested in comparing the incidence of αSN pathology in the spinal cord or PANS with that of medullary nuclei where the process of αSN aggregation is supposed to begin. αSN pathology in the shape of LN and LB was seen in 17% of individuals in our cohort, which is a higher percentage than previously reported in the substantia nigra using conventional staining methods for the detection of LB. Our main result was the high incidence of αSN pathology in the spinal cord and PANS suggesting a very early involvement of these structures next to the dorsal motor nucleus of the vagus nerve, the locus coeruleus and the olfactory nerve.

Until now the spinal cord and the PANS have not been investigated for the presence of LB or αSN immunoreactive lesions in aged neurologically unimpaired individuals. To our knowledge, the only available neuropathological studies on these structures concern subjects with clinically and morphologically well-documented cases of PD.

They all underscore the constant involvement of structures of the central and peripheral nervous system involved in autonomic regulation. In PD, LB have been amply documented in the hypothalamus [16], the intermediolateral nucleus of the thoracic spinal cord [6,11,12,17], the stellate ganglion [5], the sympathetic ganglia [17,18], the sacral parasympathetic neurones [8,9,20,21], as well as the visceral autonomic nervous system [7,22,23], and they have been considered responsible for some of the autonomic dysfunctions in PD.

Profound cardiac sympathetic denervation has been shown in PD patients by sympathetic neuroimaging [24], and post mortem immunostaining of cardiac sympathetic nerves for tyrosine hydroxylase and neurofilament antigens [25,26]. Hishikawa et al. [27] used αSN-specific antibodies to study the distribution of LB and coil-like glial inclusions in patients with Lewy body disease including PD cases. αSN positive LB were found in various grey area of the spinal cord including the posterior, lateral and anterior horns. The authors, however, did not include asymptomatic elderly control cases in their study [27].

Our finding of a near universal occurrence of αSN positive lesions in spinal cord autonomic nuclei and PANS in clinically asymptomatic ILBD cases not only underscores the findings of the studies just mentioned on subjects with PD but also points to a pathological involvement of these structures at an earlier stage probably far below disease threshold for motor symptoms of PD. It remains uncertain if our subjects with an αSN pathology in the central and peripheral autonomic nervous system have presented subjective complaints or even clinical evidence of autonomic disturbances during the latest period of their life. Although this possibility cannot be ruled out, this issue has to remain unsettled due to the mode of selection of our cases and the difficulties of retrospective anamnestic enquiry.

It was long assumed that the manifestation of autonomic failure in PD is confined to later stages of the disease. However, more recent clinical evidence supports the opposite view that manifestations of autonomic failure, including gastrointestinal, urogenital, cardiovascular, sudomotor and thermoregulatory symptoms may compromise patient's daily life activities in all stages of the disease [28,29], and are poorly correlated with parameters felt to reflect disease severity [30].

Autonomic failures have even been reported as the initial disease manifestation in some PD cases suggesting very early involvement of central and peripheral autonomic structures in PD [31]. For instance, gastrointestinal dysfunctions, especially colonic dysmotility, which are common in PD, may constitute the initial clinical feature [32].

Recent epidemiological evidence revealed that colonic dysmotility may even occur long before typical PD symptomatology. Thus, an association between the frequency of bowel movement and the risk of developing PD has been demonstrated [33].

Stomach and intestinal functions are controlled largely by the autonomic and enteric nervous system. The bulk of parasympathetic innervation of the gastrointestinal tract is derived from the dorsal motor nucleus of the vagus nerve which supplies the stomach, small intestine and proximal colon.

Parasympathetic supply to the middle and distal colon is via sacral nerves and ultimately comes from the parasympathetic autonomic nuclei of the sacral cord. Early pathological changes in the dorsal motor nucleus of the vagus nerve have been well documented [2], and we now demonstrate for the first time that sacral parasympathetic autonomic supply is involved in a very early prodromal phase of the disease.

The observed changes in both autonomic centres are likely to be responsible for parasympathetic denervation of the gut and are therefore likely to account for early gastrointestinal disturbances in PD. However, we also found early αSN abnormalities within the gut itself which may also contribute to early autonomic dysfunction in PD.

A systematic study on a cohort of cases with ILBD ranging from 54 to 86 years at death was recently performed using αSN immunohistochemistry [2].

The main result of this study was that the very earliest αSN pathology of PD displays a marked preference for specific classes of brainstem neurones including the noncatecholaminergic projection cells of the dorsal motor nucleus of the glossopharyngeal and vagal nerves, the intermediate reticular zone, the pigmented cells of the locus coeruleus and for the olfactory bulb and tract.

Based on observations of post mortem tissues from diagnosed sporadic PD cases as well as from patients without clinical signs of PD, a successive propagation of αSN pathology from the medulla oblongata to telencephalic structures in end-stage PD has been proposed [3]. In the present study we found a distribution pattern of αSN positive lesions which is well compatible with an initiation of αSN pathology in the lower brainstem and a subsequent spreading pattern to more upward located regions of the central nervous system.

However, stageing was difficult in some of our cases as αSN pathology did not follow the predicted caudo-rostral spreading pathway suggested by Braak et al. [3]. Thus, in six ILBD cases less vulnerable structures were affected in the absence of LB and LN in regions considered more vulnerable to αSN pathology.

Nevertheless, the findings by Del Tredici et al. [2], Braak et al. [3], as well as our own results, are challenging the traditional view that SNpc is the region mainly and most early affected in PD, but are compatible with the well-known fact that nigral damage is always accompanied by extensive extranigral pathology, including that in lower brainstem regions.

Our results do not allow to pinpoint the precise induction site of αSN pathology among the lower parts of the central nervous system including the spinal cord and the medulla as there were no cases among the studied cohort with isolated spinal or medullary pathology. However, the average densities of αSN positive lesions were generally higher in the lower brainstem, particularly in the region of the dorsal motor nucleus of the vagus nerve, than in the spinal cord nuclei.

This suggests that the disease process may start in lower brainstem and subsequently pursue both an ascending course to more rostrally situated brainstem nuclei and a descending course towards the spinal cord. To solve this issue will probably need a much larger cohort of elderly as well as younger ILBD subjects to be included in future studies.