Protective Activity of Aβ on Cell Cultures (PC12 and THP-1 after Differentiation) Preincubated with Lipopolysaccharide (LPS)

Abstract

Amyloid-β (Aβ), the influence of which is considered the pathomechanism of Alzheimer’s disease, is also present in healthy people. The microbiome’s impact is also taken into account, where bacterial lipopolysaccharide (LPS) activates inflammatory processes and stimulates microglia via TLRs. Molecules of bacterial origin can co-create senile plaques with Aβ. This study evaluated the activity of physiological Aβ concentrations on neuronal and microglial cells after preincubation with LPS. Two cell lines were used in the study: PC12 cells differentiated with NGF and THP-1 cells differentiated with phorbol 12-myristate 13-acetate (PMA). Cells were incubated with LPS at concentrations of 1–100 μM for 24 h and then with Aβ25–35 at a concentration of 0.001 μM or 1.0 μM for another 24 h. The viability of the culture and free oxygen radicals and the number of DNA strand breaks in both cell lines were evaluated. Additionally, for PC12 cells, neural features were assessed. Stimulation of repair processes in the presence of Aβ was observed for both studied cell lines. There was a decrease in free radical level and DNA damage number compared to control cultures (cells treated with LPS and without Aβ). The neurotrophic activity of Aβ was observed—the effect on neurites’ growth even after the preincubation of PC12 cells with LPS. At the lowest concentration of LPS used, the increase in neurite length was about 50% greater than in the negative control. At low concentrations, Aβ has a protective effect on neuron-like PC12 cells pretreated with LPS.

PC12 and THP-1 Cell Lines as Neuronal and Microglia Model in Neurobiological Research

“…At higher concentrations, Aβ25-35 caused adverse effects. The physiological concentrations of Aβ25-35 showed neuroprotective and neurotrophic effects similar to those observed in our previous study [32]. These findings seem to be in line with the recent shift in the perception of amyloid β, from the purely pathological and hallmark of disease to a potential antimicrobial peptide necessary for the brain's proper functioning [33,34].…”

“…In our opinion, the time of differentiation should be at least 72 h [15]. Therefore, the time of 72 h was chosen in this study, examining the effect of differentiation on sensitivity to harmful factors (LPS and Aβ [25][26][27][28][29][30][31][32][33][34][35].…”

“…3.6. THP-1 Cells and Amyloid β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) Incubation of THP-1 cells with amyloid β (25-35) caused a significant decrease in mitochondrial metabolic activity (measured in the MTT assay) in all tested cases except for 0.001 μM Aβ25-35 concentration in differentiated cells (up to 16.4% or 15.2% at 5 μM Aβ25-35, respectively). However, the differences depending on cell differentiation were small and statistically insignificant (Figure 7A).…”

Can Control Infections Slow Down the Progression of Alzheimer’s Disease? Talking About the Role of Infections in Alzheimer’s Disease

“…Previously, our study displayed that major inflammatory cytokines, IL-12, and IFN-γ in brain of transgenic mice APP SWE (Tg2576) that overexpress the human Aβ precursor protein gene as an AD mouse model were associated with Aβ plaque formation and microglial and astrocyte activation (Abbas et al, 2002). In the brains of patients with AD and its animal models, infection stimulating microglia and/or microglial activation by peripheral cytokines caused robust production of free radicals with another wave of pro-inflammatory cytokines, which, in turn, led to inflammation and massive neuronal damage (Nakamura et al, 2021;Wiatrak and Balon, 2021).…”

Anti-Inflammatory Properties of Statin-Loaded Biodegradable Lecithin/Chitosan Nanoparticles: A Step Toward Nose-to-Brain Treatment of Neurodegenerative Diseases

“…To evaluate the impact of SVT-LCNs on cell viability, human monocyte-derived macrophages THP-1 were used. These cells are widely accepted as the surrogate of microglial cells to evaluate cytokine secretion in the context of neuroinflammation in AD (McFarland et al, 2017;Wiatrak and Balon, 2021). THP-1 monocytes were cultured in RPMI 1640 medium supplemented with 10% FCS at 37°C in 5% CO 2 .…”