The possible role of CREB‐BDNF signaling pathway in neuroprotective effects of minocycline against alcohol‐induced neurodegeneration: molecular and behavioral evidences

Motaghinejad, Majid; Mashayekh, Roya; Motevalian, Manijeh; Safari, Sepideh

doi:10.1111/fcp.12584

Cited by 24 publications

(21 citation statements)

References 88 publications

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“…A previous study found that LPS-induced depression-like behaviour in mice by decreasing CREB and BDNF expressions in the prefrontal cortex (PFC) and hippocampus [ 4 ]. Minocycline treatment can protect methylphenidate- [ 34 ] and alcohol- [ 24 ] induced neurodegeneration in the rat brain by upregulating CREB and BDNF expressions. In a rat model of chronic, unpredictable, stress-induced depression, memantine treatment was shown to have an antidepressant-like effect by preventing hippocampus mitochondrial dysfunction and memory impairment via the upregulation of the CREB/BDNF signalling pathway [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the developing research has been focusing on its neuroprotective properties in in vivo and in vitro animal models, as well as in clinical studies [ 21 , 22 ]. Recent studies have shown that minocycline can improve synaptic transmission and integrity, as well as neurologic function via reductions in phosphorylated tau protein levels and the upregulation of BDNF/CREB signalling pathways in several animal models [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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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)

Qaid

Abdullah

Zakaria

et al. 2022

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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)

Qaid

Abdullah

Zakaria

et al. 2022

IJMS

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“…Additionally, adult rats treated with clozapine, a treatment for schizophrenia and bipolar disorder, showed upregulation of both iPLA2 and BDNF messages and protein (Kim et al, 2012). Furthermore, in adult animal models, repetitive or semichronic alcohol exposures (sometimes at unspecified BACs) have been linked to brain BDNF reductions (Davis, 2008; Motaghinejad et al, 2021; Palmisano & Pandey, 2017; Xu et al, 2015). Consequently, a reasonable hypothesis to be tested in our semi‐chronic binge model emerges: moderate BACs trigger depletion of both brain BDNF and linked iPLA2 levels that are thwarted by DHA supplementation, such that BDNF might thus be a key DHA‐responsive modulator of molecular events facilitating iPLA2 normalization.…”

Section: Discussionmentioning

confidence: 99%

Moderate blood alcohol and brain neurovulnerability: Selective depletion of calcium‐independent phospholipase A2, omega‐3 docosahexaenoic acid, and its synaptamide derivative as a potential harbinger of deficits in anti‐inflammatory reserve

Schreiber

Tajuddin

Kouzoukas

et al. 2021

Alcoholism Clin & Exp Res

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Background: Repetitive, highly elevated blood alcohol (ethanol) concentrations (BACs) of 350 to 450 mg/dl over several days cause brain neurodegeneration and coincident neuroinflammation in adult rats localized in the hippocampus (HC), temporal cortex (especially the entorhinal cortex; ECX), and olfactory bulb (OB). The profuse neuroinflammation involves microgliosis, increased proinflammatory cytokines, and elevations of Ca +2 -dependent phospholipase A2 (cPLA2) and secretory PLA2 (sPLA2), which both mobilize proinflammatory ω-6 arachidonic acid (ARA). In contrast, Ca +2independent PLA2 (iPLA2) and anti-inflammatory ω-3 docosahexaenoic acid (DHA), a polyunsaturated fatty acid regulated primarily by iPLA2, are diminished. Furthermore, supplemented DHA exerts neuroprotection. Given uncertainties about the possible effects of lower circulating BACs that are common occurring during short-term binges, we examined how moderate BACs affected the above inflammatory events, and the impact of supplemented DHA. Methods and results:Young adult male rats sustaining upper-moderate BACs (~150 mg/dl) from once-daily alcohol intubations were sacrificed with appropriate controls after 1 week. The HC, ECX and OB were quantitatively examined using immunoblotting, neurodegeneration staining, and lipidomics assays. Whereas neurodegeneration, increases in cPLA2 IVA, sPLA2 IIA, and ARA, and microglial activation were not detected, the HC and ECX regions demonstrated significantly reduced iPLA2 levels. Levels of DHA and synaptamide, its anti-inflammatory N-docosahexaenoylethanolamide derivative, also were lower in HC, and DHA supplementation prevented the iPLA2 decrements in HC. Additionally, adult mice maintaining upper-moderate BACs from limited alcohol binges had reduced midbrain iPLA2 levels. Conclusions:The apparently selective depletion by moderate BACs of the metabolically linked anti-inflammatory triad of hippocampal iPLA2, DHA, and synaptamide, and of iPLA2 in the ECX, potentially indicates an unappreciated deficit in brain antiinflammatory reserve that may be a harbinger of regional neurovulnerability.

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“…Recently, the developing research is focusing on its neuroprotective properties in in vivo and in vitro animal models as well as in clinical studies. Recent studies showed that minocycline improved synaptic transmission and integrity as well as neurologic function via reduction of phosphorylated tau protein level and upregulation of BDNF/CREB signalling pathways in several animal models (Motaghinejad et al, 2021;Salehi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Minocycline attenuates lipopolysaccharide-induced locomotor deficit and anxiety-like behavior via upregulation of the BDNF/CREB protein expression in the rat medial prefrontal cortex (mPFC)

Qaid

Abdullah

Zakaria

et al. 2022

Preprint

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Introduction: Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficit and anxiety-like behavior. In this study, minocycline was compared to memantine, the NMDA receptor antagonist, for its effects on LPS-induced locomotor deficit and anxiety-like behavior in rats. Methodology: 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 LPS (5 mg/kg, i.p.) injection. The locomotor activity and anxiety-like behavior 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 protein (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and western blot, respectively. Results: In the mPFC, minocycline treatment reduced the locomotor deficit and anxiety-like behavior, reduced phosphorylated tau protein level, and upregulated BDNF/CREB protein expression comparable to memantine, with the higher dose of minocycline having better benefits. Conclusion: Minocycline treatment attenuated LPS-induced locomotor deficit and anxiety-like behavior in rats, possibly via a decrease in phosphorylated tau protein levels and an increase in the expression of the BDNF/CREB proteins.

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The possible role of CREB‐BDNF signaling pathway in neuroprotective effects of minocycline against alcohol‐induced neurodegeneration: molecular and behavioral evidences

Cited by 24 publications

References 88 publications

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)

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)

Moderate blood alcohol and brain neurovulnerability: Selective depletion of calcium‐independent phospholipase A2, omega‐3 docosahexaenoic acid, and its synaptamide derivative as a potential harbinger of deficits in anti‐inflammatory reserve

Minocycline attenuates lipopolysaccharide-induced locomotor deficit and anxiety-like behavior via upregulation of the BDNF/CREB protein expression in the rat medial prefrontal cortex (mPFC)

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