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Intranasal Artesunate Ameliorates Hippocampal LFP Abnormalities and Cellular Apoptosis in APP/PS1 Mice via a Mechanism Involving GHRH/PI3K/Akt Signaling

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Alzheimer’s disease (AD) is characterized by neuronal damage and abnormal electroencephalogram (EEG) activity.

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While Artesunate (ART) exhibits neuroprotective properties, its specific effects on local field potentials (LFPs) and the underlying molecular mechanisms remain unclear. In this study, we investigated the therapeutic effects and mechanisms of ART in AD models.

In vivo electrophysiological recordings in freely moving APP/PS1 mice revealed that ART attenuated the “EEG slowing” phenotype by rebalancing the LFP power spectral distribution. Furthermore, ART modulated theta-gamma phase-amplitude coupling (PAC) and ameliorated specific physiological properties of sharp-wave ripples (SWRs). Concurrently, morphological and ultrastructural analyses demonstrated that ART attenuated neuronal apoptosis and mitigated pathological alterations in myelin sheaths, synapses, and mitochondria in the hippocampus.

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Mechanistically, transcriptome analysis identified growth hormone-releasing hormone (GHRH) as a primary target of ART intervention. In Aβ1-42-treated HT22 cells, ART improved cell viability. Pharmacological inhibition assays indicated that the anti-apoptotic effects of ART are mediated via the GHRH-PI3K-Akt signaling axis.

Activation of this pathway induced the inhibitory phosphorylation of GSK-3β and promoted the nuclear translocation of NF-κB p65 to upregulate Bcl-2 expression, which collectively inhibited the caspase cascade. Collectively, these findings demonstrate that ART ameliorates abnormal EEG activity and neuronal damage in AD models through the GHRH-PI3K-Akt signaling axis, providing a mechanistic basis for its therapeutic application in AD.

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Life Sciences
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Disease 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE34675914 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title