Carbenoxolone Reverses the Amyloid Beta 1–42 Oligomer–Induced Oxidative Damage and Anxiety-Related Behavior in Rats
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The characteristic feature of Alzheimer’s disease (AD) is the deposition of amyloid beta inside the brain mainly consisting of Aβ 40 and 42 aggregates. Soluble aggregates of Aβ 42 are reported to be more toxic and exert their neurotoxicity by the induction of oxidative damage and cognitive deficits such as anxiety-like behavior. These alterations emerge due to the induction of gap junction communication through increased activity and expression of connexins such as connexin43 (Cx43) leading to the release of small neurotoxic molecules. In the present study, single intracerebroventricular (icv) injection of Aβ 42 oligomers (10 μl/rat) was used to induce oxidative damage and anxiety-related behavior in rats. Carbenoxolone (Cbx), a gap junction blocker, was tested (20 mg/kg body weight, i.p., for 6 weeks) against these alterations. Cbx supplementation reversed the Aβ 42 oligomer–induced alterations in the antioxidant defense system. The levels ROS, lipid peroxidation, and protein carbonyls were normalized with Cbx co-treatment leading to the decreased DNA fragmentation and pyknosis in different regions of the rat brain. Cbx induced the anxiolytic behavior and ameliorated the cognitive decline in rats post Aβ 42 oligomer injection. The increased expression of Cx43 post Aβ 42 oligomer injection was also reduced with Cbx supplementation, which might have inhibited the release of small neurotoxic molecules. Our results showed that Cbx prevents the Aβ 42 oligomer–induced oxidative damage and anxiety-like behavior partly by blocking the gap junction communication, which suggests that the therapeutic potential of Cbx may be explored in the progression of AD.
KeywordsAmyloid beta 1–42 Alzheimer’s disease Anxiety-like behavior Oxidative damage Gap junctions Carbenoxolone
Amyloid precursor protein
Reactive oxygen species
2, 7-Dichlorofluorescein diacetate
This work is financially supported by the University Grants Commission (UGC), New Delhi, India.
Compliance with Ethical Standards
The guidelines laid by the Ethics Committee of the Animal Care of Panjab University in accordance with the Indian national law on animal care and use were strictly followed throughout the study.
Conflict of Interest
The authors declare that they have no conflict of interest.
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