Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

David Tweedie*, Lital Rachmany, Vardit Rubovitch, Elin Lehrmann, Yongqing Zhang, Kevin G. Becker, Evelyn Perez, Jonathan Miller, Barry J. Hoffer, Nigel H. Greig, Chaim G. Pick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)170-182
Number of pages13
JournalExperimental Neurology
Volume239
Issue number1
DOIs
StatePublished - Jan 2013

Funding

FundersFunder number
Sackler School of Medicine
National Institutes of Health
National Institute on Drug Abuse
National Institute on AgingZICAG000616
Tel Aviv University

    Keywords

    • Alzheimer's disease
    • Exendin-4
    • Gene expression
    • Glucagon-like peptide-1
    • Mild traumatic brain injury (mTBI)
    • Novel object recognition

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