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Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats.

Abstract：

:Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Pang Y,Tien LT,Zhu H,Shen J,Wright CF,Jones TK,Mamoon SA,Bhatt AJ,Cai Z,Fan LW

doi

10.3390/ijms16048635

subject

Has Abstract

pub_date

2015-04-17 00:00:00

pages

8635-54

issue

4

issn

1422-0067

pii

ijms16048635

journal_volume

16

pub_type

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