Effects of subchronic dietary exposure to the engineered nanomaterials SiO2 and CeO2 in C57BL/6J and 5xFAD Alzheimer model mice

Abstract

Background There is an increasing concern about the neurotoxicity of engineered nanomaterials (NMs). To investigate the effects of subchronic oral exposures to SiO2 and CeO2 NMs on Alzheimer’s disease (AD)-like pathology, 5xFAD transgenic mice and their C57BL/6J littermates were fed ad libitum for 3 or 14 weeks with control food pellets, or pellets dosed with these respective NMs at 0.1% or 1% (w/w). Behaviour effects were evaluated by X-maze, string suspension, balance beam and open field tests. Brains were analysed for plaque load, beta-amyloid peptide levels, markers of oxidative stress and neuroinflammation. Results No marked behavioural impairments were observed in the mice exposed to SiO2 or CeO2 and neither treatment resulted in accelerated plaque formation, increased oxidative stress or inflammation. In contrast, the 5xFAD mice exposed to 1% CeO2 for 14 weeks showed significantly lower hippocampal Aβ plaque load and improved locomotor activity compared to the corresponding controls. Conclusions The findings from the present study suggest that long-term oral exposure to SiO2 or CeO2 NMs has no neurotoxic and AD-promoting effects. The reduced plaque burden observed in the mice following dietary CeO2 exposure warrants further investigation to establish the underlying mechanism, given the easy applicability of this administration method.

The olfactory working memory capacity paradigm: A more sensitive and robust method of assessing cognitive function in male 5XFAD mice

“…Typically, deficits in recognition in 5XFAD mice are observed at 6 months of age or older (Frydman-Marom et al, 2011;Wang et al, 2013). In addition, 3-month-old 5XFAD mice were assessed with the cross-maze, based on a similar principle and protocol as the Y-maze; there were not significant differences in the total number of arm entries or the rate of spontaneous alternation between 5XFAD and WT mice (Jawhar et al, 2012;Sofranko et al, 2022). Oakley et al utilized a Y-maze and found that 5XFAD mice showed normal spontaneous alternation at 2 months of age but impaired spontaneous alternation at 4-5 months of age (Oakley et al, 2006).…”

Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials

“…Furthermore, their exercise activity demonstrated improvement. [ 144 ] Moreover, CeO 2 NPs also seem to affect the brain‐derived neurotrophic factor (BDNF) pathway involved in neuronal death and neuroprotection, raising the possibility of them as therapeutic tools for AD. [ 145 ] BDNF plays a key role in the maintenance of learning and memory by regulating synaptic plasticity, neuronal maintenance, cell survival, neurotransmitters, and neurogenesis, which can improve neuroinflammation and rescue cognitive deficits in APP/PS1 mice.…”