Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-8-18
pubmed:abstractText
Dynorphins, endogenous neuropeptides found in striatonigral neurons, have been observed to exhibit dopamine-inhibitory actions and under some circumstances possess intrinsic neurotoxic activity. To test the hypothesis that dynorphin suppression mitigates effects of aging on the striatal dopaminergic system, HPLC quantitation of dopamine and related amines was performed on striatal homogenates of wild-type (WT) mice and mice lacking the prodynorphin (Pdyn) gene at varying ages. Pdyn knockout (KO) mice at 10 and 20 months show significant elevations in striatal dopamine compared to 3-month mice. Differences in tyrosine hydroxylase (TH) immunoreactivity could not account for these findings, but phosphorylation of TH at Ser40, but not Ser31, was enhanced in aged Pdyn KO mice. Systemic administration of MPTP produced significant dopamine depletion in an age-dependent manner, but Pdyn deletion conferred no protection against MPTP-induced dopamine loss, arguing against a mechanism by which Pdyn deletion enhances dopaminergic neuron survival. The above findings demonstrate an age-dependent inhibitory effect of dynorphins on striatal dopamine synthesis via modulation of TH activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2430
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
219
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
228-38
pubmed:meshHeading
pubmed-meshheading:19500577-Aging, pubmed-meshheading:19500577-Amino Acid Sequence, pubmed-meshheading:19500577-Animals, pubmed-meshheading:19500577-Corpus Striatum, pubmed-meshheading:19500577-Disease Models, Animal, pubmed-meshheading:19500577-Dopamine, pubmed-meshheading:19500577-Enkephalins, pubmed-meshheading:19500577-Female, pubmed-meshheading:19500577-Immunohistochemistry, pubmed-meshheading:19500577-Male, pubmed-meshheading:19500577-Mice, pubmed-meshheading:19500577-Mice, Knockout, pubmed-meshheading:19500577-Neural Pathways, pubmed-meshheading:19500577-Parkinsonian Disorders, pubmed-meshheading:19500577-Phosphorylation, pubmed-meshheading:19500577-Protein Precursors, pubmed-meshheading:19500577-Serine, pubmed-meshheading:19500577-Substantia Nigra, pubmed-meshheading:19500577-Tyrosine 3-Monooxygenase, pubmed-meshheading:19500577-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
Effects of prodynorphin deletion on striatal dopamine in mice during normal aging and in response to MPTP.
pubmed:affiliation
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural