Journal
BRAIN SCIENCES
Volume 11, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/brainsci11121617
Keywords
clobenpropit; lipopolysaccharides; radial arm maze; cyclooxygenase-2; pro-inflammatory cytokines; anti-inflammatory cytokines; mitochondrial dysfunction
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Funding
- Deanship of Scientific Research, Qassim University, Saudi Arabia [5601-pharmacy-2019-2-2-I]
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Clobenpropit (CLO) has shown neuroprotective effects against LPS-induced cognitive deficits by improving memory behaviors, mitigating neuroinflammation, and restoring mitochondrial respiratory chain complex (MRCC) enzymes in mice.
Clobenpropit (CLO), an antagonist on histamine H-3 receptors (HH3R), has been shown to protect NMDA-induced neuronal necrosis in cortical neuronal cell culture from rats. In this work, we explored its potential on lipopolysaccharide (LPS)-induced memory deficits, neuroinflammation, and mitochondrial dysfunction in mice. CLO (1 and 3 mg/kg, p.o.) was treated continually for 30 days, and neurotoxicity was induced by four doses of LPS (250 mu g/kg, i.p.). The radial arm maze (RAM) was used to access memory behaviors. After the REM test, brain tissue was collected from each mouse to estimate pro-inflammatory cytokines (TNF alpha and IL6), anti-inflammatory cytokines (TGF-beta 1 and IL-10), cyclooxygenase-2 (COX 2), and mitochondrial respiratory chain complex (MRCC- I, II and IV) enzymes. CLO treatment reversed the LPS-induced behavioral deficits by a significant reduction in time taken to consume all five bites (TTB), working memory error (WME), and reference memory error (REM) in the REM test. Regarding neuroinflammation, it attenuated the release of COX, TNF-alpha, and IL-6, and augmented TGF-beta 1 and IL-10 levels in the brain. Reversal of LPS-induced brain MRCC (I, II, and IV) levels also resulted with CLO treatment. From these findings, CLO promises neuroprotection against LPS-induced cognitive deficits by ameliorating neuroinflammation and restoring the MRCC enzymes in mice.
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