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S013-1

Hyperbilirubinemia and Neuroinflammation in Schizophrenia: Evaluation of
Animal Studies

Kristian Liaury

Hasanuddin University, Makassar, Indonesia, Indonesia

Background/Objective: Schizophrenia is a chronic and devastating illness,affects approximately
1% of the world population with etiology that remains unclear. Accumulating evidence indicates that
neuroinflammation plays a significant role in the pathophysiology of schizophrenia. Previous studies
reported cytotoxic effects of unconjugated bilirubin (UCB) in the developing central nervous system
(CNS) that cause a neuroinflammation process, which might be indicated in the course of
schizophrenia. Neuroinflammation is characterized by the activation of microglial cells,However, it
is not fully understood how the microglia cells respond on the cytotoxic effects of UCB in the CNS.

Method: In our study, we elucidated the morphological features of microglial cells in the
hippocampal dentate gyrus of animal model of hyperbilirubinemia (Gunn rat).Using
immunohistochemical technique, we examined the distribution and morphology of ionized calcium
binding adaptor molecule1-labeled cells in the adult dentate gyrus of Gunn rats.Then, we examined
the effects of minocycline on behavioral tests microglial activation in Gunn rat. Minocycline is the
second generation of tetracycline with potent anti-inflammatory properties.After administration of
minocycline for 14 consecutive days,samples underwent behavior test and later we will examine the
microglial cells in the hippocampal dentate gyrus.

Result: As results, Iba1-labeled cell bodies and processes were distributed throughout the dentate
gyrus.Many of the Iba1-labeled cells in the hilus and the subgranular zone showed an active state,
while most of those in the molecular layer were classified into the resting type.Furthermore, we
found that administration of minocycline for 14 days significantly improved the behavior
performances in Gunn rats. Immunohistochemistry analysis revealed that microglial cells in the
minocycline-treated Gunn rat group showed less expression of CD11b compared to vehicle-treated
Gunn and Wistar control groups.

Conclusion: These results suggest that the microglial cells in Gunn rats play an important role in the
neuroinflamation and minocycline may be a potential therapeutic drug for schizophrenia by
attenuating the microglial activation.