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-   -   NEED HELP in finding report of study using byetta in Parkinson's mice (https://www.neurotalk.org/parkinson-s-disease/27716-help-finding-report-study-using-byetta-parkinsons-mice.html)

olsen 09-09-2007 09:35 PM

NEED HELP in finding report of study using byetta in Parkinson's mice
 
Was recently told about a report of a study from one of the Scandanavian countries (probalby Sweden) in which Byetta, an incretin mimetic, was used for an animal with PD symptoms
(??mice with parkinsonism induced by MPTP). The study showed very positive results. I have searched pubmed and google scholar, to no avail. I have a few other avenues ( all are very involved) , so thought I would ask if anyone on this board is able to access the report, and would be willing to assist me. If I am able to obtain the reference, I can get a copy of the report, provided it is in english. thanks in advance for any assistance. Meanwhile, I did find the following which directly deals with a glucagon like peptide and neurotrophic properties... madelyn

J Pharmacol Exp Ther. 2002 Mar;300(3):958-66.
A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells.Perry T, Lahiri DK, Chen D, Zhou J, Shaw KT, Egan JM, Greig NH.

Section of Drug, Design, and Development, Laboratory of Neuroscience, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. perryt@grc.nia.nih.gov

The insulinotropic hormone glucagon-like peptide-1 (7-36)-amide (GLP-1) has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation and is presently in clinical trials as a therapy for type 2 diabetes mellitus. We report on the effects of GLP-1 and two of its long-acting analogs, exendin-4 and exendin-4 WOT, on neuronal proliferation and differentiation, and on the metabolism of two neuronal proteins in the rat pheochromocytoma (PC12) cell line, which has been shown to express the GLP-1 receptor. We observed that GLP-1 and exendin-4 induced neurite outgrowth in a manner similar to nerve growth factor (NGF), which was reversed by coincubation with the selective GLP-1 receptor antagonist exendin (9-39). Furthermore, exendin-4 could promote NGF-initiated differentiation and may rescue degenerating cells after NGF-mediated withdrawal. These effects were induced in the absence of cellular dysfunction and toxicity as quantitatively measured by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays, respectively. Our findings suggest that such peptides may be used in reversing or halting the neurodegenerative process observed in neurodegenerative diseases, such as the peripheral neuropathy associated with type 2 diabetes mellitus and Alzheimer's and Parkinson's diseases. Due to its novel twin action, GLP-1 and exendin-4 have therapeutic potential for the treatment of diabetic peripheral neuropathy and these central nervous system disorders.

PMID: 11861804 [PubMed - indexed for MEDLINE]

olsen 09-09-2007 09:36 PM

Swedes Show Byetta Cures Parkinson's Disease in Rats
 
OH GEEZ--found it in the financial section!

Swedes Show Byetta Cures Parkinson's Disease in Rats (2 Ratings) 7-Sep-07 06:10 pm Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of parkinson's disease.

Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J, Kortesmaa J, Mercer A, Nielsen E, R?olm H, Wikstr?.

NeuroNova AB, Stockholm, Sweden.

We investigated the effects of exendin-4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP-1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region.

In vitro, exendin-4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and neuron-specific enolase.

When exendin-4 was given intraperitoneally to naive rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine-positive cells and the number of neuronal precursor cells expressing doublecortin were increased.

Exendin-4 was tested in the 6-hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5-week stabilization period, the rats were treated for 3 weeks with exendin-4. We found a reduction of amphetamine-induced rotations in animals receiving exendin-4 that persisted for several weeks after drug administration had been terminated.

Histological analysis showed that exendin-4 significantly increased the number of both tyrosine hydroxylase- and vesicular monoamine transporter 2-positive neurons in the substantia nigra.

In conclusion, our results show that exendin-4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease.


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