Page 78 - Q. Neuroscience

[Q. Neuroscience-45]

TNF-α signaling and mitochondrial unfolded protein

response involved in the pathogenesis of hydrocephalus

Jie bo Zhu¹˙²˙³˙#, Min Joung Lee¹˙²˙³˙#, Hee Jin Chang¹˙⁴, Soo Jeong Kim¹˙²˙³, Yun seon Jang¹˙²˙³, Xian shu Ju¹˙³,
Jian chen Cui¹˙³, Yu Lim Lee¹˙³, Eun ji Namgung¹˙²˙³, Da hyun Go¹˙²˙³, Chang jun Seo¹˙²˙³, Woo suk Chung¹˙⁵˙⁶,
Eung seok Oh¹˙⁴, Jun Young Heo¹˙²˙³˙*

¹Department of Medical science, Chungnam National University School of Medicine, Daejeon 35015, South Korea,
²Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, South Korea,
³Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon
35015, South Korea, ⁴Department of Neurology, Chungnam National University Hospital, Daejeon 35015, South
Korea, ⁵Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine,

Daejeon 35015, South Korea, ⁶Department of Anesthesiology and Pain Medicine, Chungnam National University
Hospital, Daejeon 35015, South Korea

Background: Hydrocephalus is cerebral spinal fluid (CSF) excessive accumulation, resulting in abnormal expansion
of ventricles. Inflammation and pathological mitochondria had been observed in hydrocephalus patients. However,
inflammatory and mitochondrial underlying mechanisms are still unknown.

Objective: To identify the role of tumor necrosis factor (TNF)-α signaling, and mitochondrial unfolded protein
responses (UPRmt) in kaolin induced hydrocephalic mouse model.

Methods: Generated hydrocephalic model, by injected 25% kaolin into C57BL/6J mice cisterna magna with

stereotactic surgery. Western blotting, qRT-PCR, ELISA, and immunofluorescence to assess the expression of TNF-α
signaling and UPRmt.

Results: Kaolin induced hydrocephalic mice showed that the weight decreased, ventricular dilatation, motor behavior
defects, and the neurologic score showed ataxia. TNF-α activated nuclear factor-κB (NF-κB) signaling promotes
proinflammatory cytokine expression. TNF-α, NF-κB, and pNF-κB showed co-expression with glia cells. Accompanied
by UPRmt protein and mRNA expression increased.

Conclusions: TNF-α signaling and UPRmt mediated kaolin induced hydrocephalic mouse model. Our findings

provide new sights for the treatment of hydrocephalus.