PMID- 19164583
OWN - NLM
STAT- MEDLINE
DCOM- 20090213
LR  - 20220408
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 4
DP  - 2009 Jan 27
TI  - GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in 
      cellular and rodent models of stroke and Parkinsonism.
PG  - 1285-90
LID - 10.1073/pnas.0806720106 [doi]
AB  - Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted 
      from the gastrointestinal tract in response to food intake. It enhances 
      pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, 
      and lowers blood glucose and food intake in patients with type 2 diabetes 
      mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), 
      is the first of this new class of antihyperglycemia drugs approved to treat T2DM. 
      GLP-1Rs are coupled to the cAMP second messenger pathway and, along with 
      pancreatic cells, are expressed within the nervous system of rodents and humans, 
      where receptor activation elicits neurotrophic actions. We detected GLP-1R mRNA 
      expression in both cultured embryonic primary cerebral cortical and ventral 
      mesencephalic (dopaminergic) neurons. These cells are vulnerable to hypoxia- and 
      6-hydroxydopamine-induced cell death, respectively. We found that GLP-1 and Ex-4 
      conferred protection in these cells, but not in cells from Glp1r knockout (-/-) 
      mice. Administration of Ex-4 reduced brain damage and improved functional outcome 
      in a transient middle cerebral artery occlusion stroke model. Ex-4 treatment also 
      protected dopaminergic neurons against degeneration, preserved dopamine levels, 
      and improved motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 
      (MPTP) mouse model of Parkinson's disease (PD). Our findings demonstrate that 
      Ex-4 can protect neurons against metabolic and oxidative insults, and they 
      provide preclinical support for the therapeutic potential for Ex-4 in the 
      treatment of stroke and PD.
FAU - Li, Yazhou
AU  - Li Y
AD  - Laboratory of Neurosciences, Intramural Research Program, National Institute on 
      Aging, Baltimore, MD 21224, USA.
FAU - Perry, TracyAnn
AU  - Perry T
FAU - Kindy, Mark S
AU  - Kindy MS
FAU - Harvey, Brandon K
AU  - Harvey BK
FAU - Tweedie, David
AU  - Tweedie D
FAU - Holloway, Harold W
AU  - Holloway HW
FAU - Powers, Kathleen
AU  - Powers K
FAU - Shen, Hui
AU  - Shen H
FAU - Egan, Josephine M
AU  - Egan JM
FAU - Sambamurti, Kumar
AU  - Sambamurti K
FAU - Brossi, Arnold
AU  - Brossi A
FAU - Lahiri, Debomoy K
AU  - Lahiri DK
FAU - Mattson, Mark P
AU  - Mattson MP
FAU - Hoffer, Barry J
AU  - Hoffer BJ
FAU - Wang, Yun
AU  - Wang Y
FAU - Greig, Nigel H
AU  - Greig NH
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20090121
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glp1r protein, mouse)
RN  - 0 (Glp1r protein, rat)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (Venoms)
RN  - 9P1872D4OL (Exenatide)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - Animals
MH  - Brain Infarction/drug therapy/pathology
MH  - Cell Death/drug effects
MH  - Cell Hypoxia/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - *Cytoprotection/drug effects
MH  - Disease Models, Animal
MH  - Dopamine/*metabolism
MH  - Embryo, Mammalian/cytology
MH  - Exenatide
MH  - Gene Expression Regulation/drug effects
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Humans
MH  - Mesencephalon/cytology
MH  - Mice
MH  - Neurons/drug effects/*pathology
MH  - Parkinson Disease/drug therapy/metabolism/*pathology
MH  - Peptides/pharmacology/therapeutic use
MH  - Rats
MH  - Receptors, Glucagon/genetics/*metabolism
MH  - Stroke/drug therapy/metabolism/*pathology
MH  - Treatment Outcome
MH  - Venoms/pharmacology/therapeutic use
PMC - PMC2633544
COIS- The authors declare no conflict of interest.
EDAT- 2009/01/24 09:00
MHDA- 2009/02/14 09:00
PMCR- 2009/07/27
CRDT- 2009/01/24 09:00
PHST- 2009/01/24 09:00 [entrez]
PHST- 2009/01/24 09:00 [pubmed]
PHST- 2009/02/14 09:00 [medline]
PHST- 2009/07/27 00:00 [pmc-release]
AID - 0806720106 [pii]
AID - 6439 [pii]
AID - 10.1073/pnas.0806720106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1285-90. doi: 
      10.1073/pnas.0806720106. Epub 2009 Jan 21.