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Fulltext Minocycline Attenuates Lipopolysaccharide-Induced Locomotor Deficit and Anxiety-like Behavior and Related Expression of the BDNF/CREB Protein in the Rat Medial Prefrontal Cortex (mPFC)

Abdo Qaid EY, Abdullah Z, Zakaria R, Long I

Int J Mol Sci, 2022 Nov 03;23(21).
PMID: 36362262 DOI: 10.3390/ijms232113474

Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits and anxiety-like behaviour. In this study, minocycline was compared to memantine, an NMDA receptor antagonist, for its effects on LPS-induced locomotor deficits and anxiety-like behaviour in rats. Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to an LPS (5 mg/kg, i.p.) injection. Locomotor activity and anxiety-like behaviour were assessed using the open-field test (OFT). The phosphorylated tau protein level was measured using ELISA, while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and Western blot, respectively. Minocycline treatment reduced locomotor deficits and anxiety-like behaviour associated with reduced phosphorylated tau protein levels, but it upregulated BDNF/CREB protein expressions in the mPFC in a comparable manner to memantine, with a higher dose of minocycline having better benefits. Minocycline treatment attenuated LPS-induced locomotor deficits and anxiety-like behaviour in rats and decreased phosphorylated tau protein levels, but it increased the expressions of the BDNF/CREB proteins in the mPFC.
Minocycline mitigates tau pathology via modulating the TLR-4/NF-кβ signalling pathway in the hippocampus of neuroinflammation rat model

Abdo Qaid EY, Abdullah Z, Zakaria R, Long I

Neurol Res, 2024 Mar;46(3):261-271.
PMID: 38122814 DOI: 10.1080/01616412.2023.2296754

INTRODUCTION: The neuroinflammatory response was seen to impact the formation of phosphorylated tau protein in Alzheimer's disease (AD). This study aims to investigate the molecular mechanism of minocycline in reducing phosphorylated tau protein formation in the hippocampus of lipopolysaccharide (LPS)-induced rats.
METHODS: Fifty adult male Sprague Dawley (SD) rats were randomly allocated to 1 of 5 groups: control, LPS (5 mg/kg), LPS + minocycline (25 mg/kg), LPS + minocycline (50 mg/kg) and LPS + memantine (10 mg/kg). Minocycline and memantine were administered intraperitoneally (i.p) for two weeks, and LPS was injected i.p. once on day 5. ELISA was used to determine the level of phosphorylated tau protein in SD rats' hippocampal tissue. The density and expression of Toll-like receptor-4 (TLR-4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кβ), tumour necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2 were determined using Western blot and immunohistochemistry.
RESULTS: Minocycline, like memantine, prevented LPS-induced increasein phosphorylated tau protein level suggested via reduced density and expression of TLR-4, NF-кβ, TNF-αand COX-2 proteins in rat hippocampal tissue. Interestingly, higher doses were shown to be more neuroprotective than lower doses.
CONCLUSION: This study suggests that minocycline suppresses the neuroinflammation signalling pathway and decreased phosphorylated tau protein formation induced by LPS in a dose-dependent manner. Minocycline can be used as a preventative and therapeutic drug for neuroinflammatory diseases such as AD.
Minocycline protects against lipopolysaccharide-induced glial cells activation and oxidative stress damage in the medial prefrontal cortex (mPFC) of the rat

Abdo Qaid EY, Abdullah Z, Zakaria R, Long I

Int J Neurosci, 2024 Jun;134(1):56-65.
PMID: 35638219 DOI: 10.1080/00207454.2022.2084092

PURPOSE/AIM: Neuroinflammation and oxidative stress have been encountered in neurodegenerative diseases such as Alzheimer's disease (AD). However, the neuroprotective effects of minocycline against lipopolysaccharide (LPS)-induced glial cells activation and oxidative stress damage in the medial prefrontal cortex (mPFC) of rats are still elusive. The purpose of this study is to investigate the effects of minocycline and memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on the microglia and astrocytes expression, as well as oxidative stress levels in the mPFC of LPS injected rats.
MATERIALS AND METHODS: Fifty adult Male Sprague Dawley rats were divided into five groups: control, LPS (5 mg/kg), LPS treated with minocycline (25 mg/kg), LPS treated with minocycline (50 mg/kg) and LPS treated with memantine (10 mg/kg). The immunohistochemistry and western blotting were used to analyse the expressions and densities of microglia marker (Iba-1) and astrocyte marker, (GFAP) while enzyme-linked immunosorbent assay (ELISA) was used to measure the protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels.
RESULTS: In comparison to the control group, the expression and density of Iba-1 and GFAP were significantly enhanced in the LPS group (p
The role of mTOR signalling pathway in hypoxia-induced cognitive impairment

Abdo Qaid EY, Zulkipli NN, Zakaria R, Ahmad AH, Othman Z, Muthuraju S, et al.

Int J Neurosci, 2021 May;131(5):482-488.
PMID: 32202188 DOI: 10.1080/00207454.2020.1746308

Hypoxia has been associated with cognitive impairment. Many studies have investigated the role of mTOR signalling pathway in cognitive functions but its role in hypoxia-induced cognitive impairment remains controversial. This review aimed to elucidate the role of mTOR in the mechanisms of cognitive impairment that may pave the way towards the mechanistic understanding and therapeutic intervention of hypoxia-induced cognitive impairment. mTORC1 is normally regulated during mild or acute hypoxic exposure giving rise to neuroprotection, whereas it is overactivated during severe or chronic hypoxia giving rise to neuronal cells death. Thus, it is worth exploring the possibility of maintaining normal mTORC1 activity and thereby preventing cognitive impairment during severe or chronic hypoxia.