2022
DOI: 10.1038/s41398-022-01908-y
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Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits

Abstract: The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired… Show more

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Cited by 7 publications
(7 citation statements)
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“…In particular, subpopulation 20 exhibited differential expression of the signature proteins NECTIN1, PLAUR and DSC3 in the APP/PS1 AD model and control groups (Figure 3d) and had a lower quantity of EVs in the model mice than in the control mice (Figure 3e), which could be attributed to the lower numbers of NECTIN1 + and PLAUR + EVs in the total urinary EVs and in multiple EV subpopulations of AD model mice (Figure 3f,g). Given that the NECTIN1/NECTIN family and PLAU/PLAUR are involved in synaptic formation and amyloid-β processing (Ertekin-Taner et al, 2005;Kim et al, 2002;Wu et al, 2022), our results suggest that the differentially expressed EV proteins and EV subpopulations may indicate pathological progression and serve as candidate biomarkers for AD.…”
Section:  Single Ev Analysis For Improved Diagnosis Of Ad Model Micementioning
confidence: 84%
“…In particular, subpopulation 20 exhibited differential expression of the signature proteins NECTIN1, PLAUR and DSC3 in the APP/PS1 AD model and control groups (Figure 3d) and had a lower quantity of EVs in the model mice than in the control mice (Figure 3e), which could be attributed to the lower numbers of NECTIN1 + and PLAUR + EVs in the total urinary EVs and in multiple EV subpopulations of AD model mice (Figure 3f,g). Given that the NECTIN1/NECTIN family and PLAU/PLAUR are involved in synaptic formation and amyloid-β processing (Ertekin-Taner et al, 2005;Kim et al, 2002;Wu et al, 2022), our results suggest that the differentially expressed EV proteins and EV subpopulations may indicate pathological progression and serve as candidate biomarkers for AD.…”
Section:  Single Ev Analysis For Improved Diagnosis Of Ad Model Micementioning
confidence: 84%
“…Nectin1 is expressed in both astrocytes and developing synapses between hippocampal neurons [33]. Wu, C et al [34] investigated the reduction of nectin-1 expression associated with neonatal stress, which potentially contributed to the impairments in cognitive performance and development of the entorhinal-hippocampal circuit that is critical to the mnemonic process. Sorcs2 encodes one family member of vacuolar protein sorting 10 domaincontaining receptors, is strongly expressed in hippocampal pyramidal neurons, which is a critical mediator for social memory formation by speci cally regulating NMDAR (N-methyl-D-aspartate receptor) dependent synaptic activities [35].…”
Section: Discussionmentioning
confidence: 99%
“…The type of maternal care permanently alters gene expression –an example of environmental programming ( Meaney and Szyf, 2005 ). Reduced levels of presynaptic nectin1 cell adhesion molecule in the medial entorhinal cortex lead to an impairment of spatial memory and decreased neuronal plasticity in CA1 ( Wu et al, 2022 ). Decreased expression of the developmental transcription factor Otx2 in the VTA increases stress susceptibility in adulthood following CSDS ( Peña et al, 2017 ).…”
Section: Modelling Pathogenesismentioning
confidence: 99%