Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice.
Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer's disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury.
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. tweedieda@grc.nia.nih.gov
David
D
Tweedie
Lital
L
Rachmany
Vardit
V
Rubovitch
Elin
E
Lehrmann
Yongqing
Y
Zhang
Kevin G
KG
Becker
Evelyn
E
Perez
Jonathan
J
Miller
Barry J
BJ
Hoffer
Nigel H
NH
Greig
Chaim G
CG
Pick
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D019295:Computational Biology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D000077270:Exenatide; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D021641:Recognition, Psychology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
D018076:DNA, Complementary; D018696:Neuroprotective Agents; D010455:Peptides; D014688:Venoms; D012313:RNA; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide