The detection of β-amyloid plaques in an Alzheimer's disease rat model with DDNP-SPIO

Isoflurane anesthesia has been shown to be responsible for cognitive impairment in Alzheimer’s disease (AD) and development of AD in the older age groups. However, the pathogenesis of AD-related cognitive impairments induced by isoflurane anesthesia remains elusive. Thus, this study was designed to investigate the mechanism by which isoflurane anesthesia caused AD-related cognitive impairments. Aged Wistar rats were randomly divided into 6 groups (n = 12), 1 control group (CONT) and 5 isoflurane treated (ISO) groups (ISO 0, ISO 0.5D, ISO 1D, ISO 3D and ISO 7D). The CONT group inhaled 30% O2 for 2 h without any anesthesia. ISO groups were placed under anesthesia with 3% isoflurane and then exposed to 1.5% isoflurane delivered in 30% O2 for 2 h. Rats in each ISO group were then analyzed immediately (ISO 0) or at various time points (0.5, 1, 3 or 7 day) after this exposure. Cognitive function was assessed using the Morris water maze test. Protein levels of amyloid precursor protein (APP), β-site APP cleavage enzyme-1 (BACE-1) and Aβ42 peptide were analyzed in hippocampal samples by Western blot. β-Amyloid (Abeta) plaques were detected in hippocampal sections by Congo red staining. Compared with controls, all ISO groups showed increased escape latency and impaired spatial memory. Isoflurane increased APP mRNA expression and APP protein depletion, promoting Aβ42 overproduction, oligomerization and accumulation. However, isoflurane did not affect BACE-1 expression. Abeta plaques were observed only in those ISO groups sacrificed at 3 or 7 d. Our data indicate that aged rats exposed to isoflurane had increased APP mRNA expression and APP protein depletion, with Aβ42 peptide overproduction and oligomerization, resulting in formation of Abeta plaques in the hippocampus. Such effects might have contributed to cognitive impairments, including in spatial memory, observed in these rats after isoflurane anesthesia.

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“…For Congo red staining, paraffin sections (5 μm) were treated as described [25]. Briefly, sections were deparaffinized in xylene and rehydrated.…”

Section: Methodsmentioning

confidence: 99%

Isoflurane anesthesia promotes cognitive impairment by inducing expression of β-amyloid protein-related factors in the hippocampus of aged rats

Zhang

Guan

et al. 2017

PLoS ONE

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“…For Congo red staining, paraffin sections (5 μm thick) were used as described [ 27 ]. Briefly, coronal sections were deparaffinized in xylene and rehydrated.…”

Section: Methodsmentioning

confidence: 99%

DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission and reducing neuronal loss

et al. 2019

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At present, few available drugs can be used to either improve pathological features or prevent the progression of Alzheimer’s disease (AD). DL0410 ((1,1′-([1,1′-biphenyl]-4,4′-diyl) bis (3-(piperidin-1-yl) propan-1-one) dihydrochloride) is a multiple-target small molecule that has been found to reverse cognitive impairment in different animal models of AD. In this study we evaluated the cognition-improving effects of DL0410 in APP/PS1 transgenic mice and explored the underlying mechanisms. APP/PS1 transgenic mice were administered DL0410 (3, 10, 30 mg· kg −1 · d −1 , ig) for 2 months. We found that DL0410 administration significantly ameliorated cognitive deficits in both the nest-building and Morris water maze tests. In electrophysiological analysis of hippocampal slices, we showed that DL0410 administration significantly enhanced the field EPSP slope and HFS-induced LTP in CA1 area. Furthermore, we revealed that DL0410 administration significantly increased the phosphorylation of AKT and the activity of GSK-3β in the hippocampus and cortex. Moreover, DL0410 administration dose-dependently increased the expression level of phosphorylated ERK1/2 in the hippocampus and cortex. In addition, DL0410 dose-dependently decreased the neuronal loss by decreasing the production of Aβ deposition, inhibited glial overactivation, and the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6. We conclude that DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission via activating the AKT/GSK-3β and MAPK/ERK signaling pathway and reducing neuronal loss. DL0410 may be an effective agent for AD treatment in the future.

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“…The deposition of Aβ is one of the primary histopathological characteristics of AD (Tiwari et al, 2019). With the relatively large size and being located intercellularly, Aβ can be regarded as an ideal imaging biomarker (Zhang et al, 2015). The Aβ deposition is earlier than clinical manifestations FIGURE 1 | The application of iron oxide nanoparticles (IONPs) in diagnosis and treatment of Alzheimer's disease (AD).…”

Section: Detecting Iron Deposit In Amyloid Plaques By Mrimentioning

confidence: 99%

“…By MRI, the number of plaques visible per brain was about twice in AβPP/PS1 transgenic mice than that in control AD mice (Sillerud et al, 2013). DDNP-SPION nanoparticles were further tested by intrahippocampal injection of Aβ 1-40 in a rat AD model (Zhang et al, 2015). After intravenous injection of DDNP-SPIONs in AD rats and testing by coronal T2 * -weighted images, the signal intensity (SI) detected in the hippocampal area was decreased significantly, which indicated the binding of DDNP-SPIONs to the Aβ plaques (Zhang et al, 2015).…”

Section: Iron Oxide Nanoparticles In the Diagnosis Of Ad In Vivomentioning

confidence: 99%

“…DDNP-SPION nanoparticles were further tested by intrahippocampal injection of Aβ 1-40 in a rat AD model (Zhang et al, 2015). After intravenous injection of DDNP-SPIONs in AD rats and testing by coronal T2 * -weighted images, the signal intensity (SI) detected in the hippocampal area was decreased significantly, which indicated the binding of DDNP-SPIONs to the Aβ plaques (Zhang et al, 2015). Curcumin is a natural compound that can bind to amyloid plaques specifically (Cheng et al, 2015).…”

Section: Iron Oxide Nanoparticles In the Diagnosis Of Ad In Vivomentioning

confidence: 99%

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Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer’s Disease

Luo

Zhu

et al. 2020

Front. Cell. Neurosci.

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The detection of β-amyloid plaques in an Alzheimer's disease rat model with DDNP-SPIO

Cited by 35 publications

References 47 publications

Isoflurane anesthesia promotes cognitive impairment by inducing expression of β-amyloid protein-related factors in the hippocampus of aged rats

Isoflurane anesthesia promotes cognitive impairment by inducing expression of β-amyloid protein-related factors in the hippocampus of aged rats

DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission and reducing neuronal loss

Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer’s Disease

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