Page 72 - ebook

[A. Biochemistry/Molecular Biology] A-36

Forskolin suppresses Hypoxia-Induced Cognitive

Dysfunction in Zebrafish

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Quynh T N Nguyen¹ , Jiwon Park¹ , Dong Yeol Kim¹, Sang Min Kim¹, Duong T T Tran¹, An Ngan Bui¹,
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Hyun Jae Sung¹, Inn Oc Han¹*

¹Program in Biomedical Science and Engineering, Inha University, Incheon 22212, Korea

Repeated hypoxia (RH) exposure is reported to accelerate brain inflammation, affect the initiation and progression

of cognitive dysfunction. Forskolin, an adenylate cyclase activator, is well-known to be an inductor of the
cAMP/PKA/CREB signaling. It has been shown that forskolin protects against various neuronal complications and

induces long term memory; however, the underlying mechanism remains unclear. In this study, we showed that
intraperitoneal administration of 200 ng/g forskolin for 5 days on zebrafish notably recovered hypoxia-induced

social interaction impairment and learning memory deficit. Forskolin suppressed RH-induced neuroinflammation
indicated by the decrease of NFkB signaling and GFAP expression. RH triggered downregulated expression of CREB-

dependent synaptic plasticity related genes, including C-fos and BDNF, and this was restored by forskolin. As our
previous study proposed that RH-associated downregulation of O-GlcNAcylation flux could be an important causal

factor for cognitive defect, we further investigated whether O-GlcNacylation level is changed by forskolin.
Intriguingly, we observed that forskolin elevated O-GlcNAc level both in vitro and in vivo. Under forskolin treatment,

O-GlcNacylation flux on RH-exposed zebrafish was reserved in line with the recovery of other inflammation and
learning/memory markers. Thus, we are seeking to study further about the potential regulation of O-GlcNAcylation

on the neuroprotective effect of forskolin.