TY - JOUR
T1 - Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice
AU - Tweedie, David
AU - Rachmany, Lital
AU - Rubovitch, Vardit
AU - Lehrmann, Elin
AU - Zhang, Yongqing
AU - Becker, Kevin G.
AU - Perez, Evelyn
AU - Miller, Jonathan
AU - Hoffer, Barry J.
AU - Greig, Nigel H.
AU - Pick, Chaim G.
N1 - Funding Information:
This research was supported in part by the Sackler School of Medicine, Tel-Aviv University , and the Intramural Research Programs of both the National Institute on Aging and National Institute on Drug Abuse , National Institutes of Health .
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Exendin-4
KW - Gene expression
KW - Glucagon-like peptide-1
KW - Mild traumatic brain injury (mTBI)
KW - Novel object recognition
UR - http://www.scopus.com/inward/record.url?scp=84868458245&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2012.10.001
DO - 10.1016/j.expneurol.2012.10.001
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AN - SCOPUS:84868458245
SN - 0014-4886
VL - 239
SP - 170
EP - 182
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -