[paula_w]

Stan the resource man from ppp sent this thru email. Found it interesting because it's always a combination of factors that are involved. We know our meds are overdosing us in some areas. I have some downright strange dyskinetic movements now that keep me in the house at night mostly. Are there ways to control our serotonin more efficiently? I can send the whole article if you pm me for it.


OK i was notified by the very patient and overworked copyright patrol here - that i posted too much from the article. But this patrol went so far as to find a printable source for the same article. This was a very nice surprise and thank you jo. I don't think they are going to make a habit of it....but want to express my appreciation and i won't tell anyone else besides the forum..lol.
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Impact of grafted serotonin and dopamine neurons on development of L-DOPA-induced dyskinesias in parkinsonian rats is determined by the extent of dopamine neuron degeneration.

Carlsson T, Carta M, Muñoz A, Mattsson B, Winkler C, Kirik D, Björklund A.
Department Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, BMC D11, Lund, Sweden.

Previous studies have shown that serotonin neurons play an important role in the induction and maintenance of L-DOPA-induced dyskinesia in animals with lesion of the nigrostriatal dopamine system. Patients with Parkinson's disease that receive transplants of foetal ventral mesencephalic tissue, the graft cell preparation is likely to contain, in addition to dopamine neurons, serotonin neurons that will vary in number depending on the landmarks used for dissection. Here, we have studied the impact of grafted serotonin neurons--alone or mixed with dopamine neurons--on the development of L-DOPA-induced dyskinesia in rats with a partial 6-hydroxydopamine lesion of the host nigrostriatal projection. In these rats, which showed only low-level dyskinesia at the time of transplantation, serotonin grafts induced a worsening in the severity of dyskinesia that developed during continued L-DOPA treatment, while the dopamine-rich graft had the opposite, dampening effect. The detrimental effect seen in animals with serotonin neuron grafts was dramatically increased when the residual dopamine innervation in the striatum was removed by a second 6-hydroxydopamine lesion. Interestingly, rats with grafts that contained a mixture of dopamine and serotonin neurons (in approximately 2:1) showed a marked reduction in L-DOPA-induced dyskinesia over time, and the appearance of severe dyskinesia induced by the removal of the residual dopamine innervation, seen in the animals with transplants of serotonin neurons alone, was blocked. FosB expression in the striatal projection neurons, which is associated with dyskinesias, was also normalized by the dopamine-rich grafts, but not by the serotonin neuron grafts. These data indicate that as long as a sufficient portion, some 10-20%, of the dopamine innervation still remains, the increased host serotonin innervation generated by the grafted serotonin neurons will have limited effect on the development or severity of L-DOPA-induced dyskinesias. At more advanced stages of the disease, when the dopamine innervation of the putamen is reduced below this critical threshold, grafted serotonin neurons are likely to aggravate l-DOPA-induced dyskinesia in those cases where the dopamine re-innervation derived from the grafted neurons is insufficient in magnitude or do not cover the critical dyskinesia-inducing sub-regions of the grafted putamen. We conclude that it is not the absolute number of serotonin neurons in the grafts, but the relative densities of dopamine and serotonin innervations in the grafted striatum that is the critical factor in determining the long-term effect of foetal tissue graft, beneficial or detrimental, on dyskinesia in grafted Parkinson's disease patients.

http://www.ncbi.nlm.nih.gov/pubmed/19039008
PMID: 19039008 [PubMed - in process]


Does anyone know anything about this study that could be applied in any way? It's not about med I guess, but generating chemical production in our own bodies. Is this study talking about what we call "end of dose" dyskinesia? Dyskinesia from falling level of dopamine, which allows serotonin to cause the dyskinesia?

Can serotonin be regulated in any way?

paula

[ZucchiniFlower]

I think this is the article:

http://brain.oxfordjournals.org/cgi/...ull/awn305#top

Brain Advance Access originally published online on November 27, 2008
Brain 2009 132(2):319-335; doi:10.1093/brain/awn305

Impact of grafted serotonin and dopamine neurons on development of L-DOPA-induced dyskinesias in parkinsonian rats is determined by the extent of dopamine neuron degeneration

Thomas Carlsson1,2,*, Manolo Carta1,2,, Ana Muñoz1,, Bengt Mattsson1, Christian Winkler3, Deniz Kirik2 and Anders Björklund1

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It seems that one would want a graft like this one:

"Interestingly, rats with grafts that contained a mixture of dopamine and serotonin neurons (in 2:1) showed a marked reduction in L-DOPA-induced dyskinesia over time, and the appearance of severe dyskinesia induced by the removal of the residual dopamine innervation, seen in the animals with transplants of serotonin neurons alone, was blocked."

Serotonin-rich grafts caused dyskinesias.

"Interestingly, the dampening effect on dyskinesia in the rats with DA wide grafts, i.e. grafts with mixed DA and serotonin neurons, was opposite to the worsening seen in rats with grafts containing serotonin neurons only (i.e. the 5-HT graft group)"......"This indicates that the effect of the graft-derived serotonin innervation is detrimental only in the absence of a significant functional dopaminergic input."

From the discussion:

"Clinical implications

The results show that the development of L-DOPA-induced dyskinesia in the rat Parkinson's disease model depends on a close interaction between the dopaminergic and serotonergic afferents. In non-grafted 6-OHDA lesioned rats systemic L-DOPA administration induces AIMs only when the loss of DA neurons in the SN is greater than 80% and the loss of DA innervation in the lateral part of the striatum exceeds 90% (Winkler et al., 2002). This suggests that when dyskinesias is induced in the rat model by low L-DOPA doses (6–12 mg/kg; which corresponds to the doses used clinically), as little as 10% of the normal DA innervation density in the critical, lateral dyskinesia-triggering part of the caudate–putamen may be sufficient to buffer the swings in DA released from the serotonin terminals. Since the DA innervation in the intact striatum is some 15- to 20-times higher in density than the serotonin ones (as judged by the tissue levels of DA and serotonin; see Carta et al., 2007) this suggests that a DA:serotonin terminal ratio of about 1:1, or higher, would be sufficient to keep the dyskinesias in check. Indeed, when this situation is met DA synthesized and released from the serotonin terminals might be beneficial and contribute positively to the therapeutic efficacy of L-DOPA treatment. It is interesting to compare these values, obtained in rats, with the situation in Parkinson's disease patients. Similar to the rat striatum the DA:serotonin ratio in the putamen of control human cases is about 20:1 (Kish et al., 2008). In advanced cases of Parkinson's disease the putaminal DA levels are typically reduced by more than 90% (by 98% in the Kish et al., 2008 study), while the loss of putaminal serotonin innervation (as assessed by levels of serotonin, SERT and tryptophan hydroxylase) is less, and also more variable (30–65%). As a result, the DA:serotonin ratio is reduced to an average of about 1:1 (Kish et al., 2008), i.e. within the range where dyskinesias would be expected to be held in check by the residual DA innervation. Kish et al. did not observe any difference in putaminal DA:serotonin ratio in patients with or without recorded dyskinesias, which may be explained by the fact that the tissue samples used for analysis included the whole putamen. If the induction of L-DOPA-induced dyskinesias is critically dependent on DA released in a particular, dyskinesia-prone sub-region of the putamen (as is the case in rodents; see Cenci et al., 1998) then the overall putaminal tissue levels may mask important regional differences in the DA and serotonin innervation densities that may determine the patient's sensitivity to develop dyskinetic side-effects."


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It may be a particular area of the putamen that controls the dyskinesias. So studies of the putamen as a whole may be misleading.

It's like a detective story, isn't it?