Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages

摘要

The hippocampus is a structurally and functionally complex brain area that plays important and diverse roles in higher brain functions, such as learning and memory, and mounting evidence indicates that different hippocampal subregions play distinctive roles. The hippocampus is also one of the first regions in the brain to suffer damage in Alzheimer's disease ( ). Synaptic dysfunction in the hippocampus, rather than neuronal loss , is paralleled by behavioural and functional deficits in . The membrane‐associated guanylate kinase ( ) family of proteins, including 102, ‐95, ‐93 and 97, have long been recognized as essential components of the postsynaptic density ( ) at excitatory synapses. Hippocampal spines are the predominant synaptic transmission sites of excitatory glutamatergic synapses. During postnatal brain development, individual members show distinct expression patterns. Although 102 has been confirmed as the dominant scaffold protein in neonatal synapses, its expression profiles in adult and ageing rodent hippocampi are discrepant. Furthermore, in brains, significantly reduced 102 protein levels have been found, suggesting that 102 may be related to progression; however, the precise mechanism underlying this result remains unclear. Herein, we observed distinct 102 expression profiles in the hippocampal 1, 3 and subregions of rats and swe/ 1dE9 ( / 1) mice at various ages using immunofluorescence. In Wistar rats, 102 was not only highly expressed in the hippocampal subregions of neonatal rats but also maintained relatively high expression levels in adult hippocampi and displayed no obvious decreases in the 1 and subregions of aged rats. Surprisingly, we observed abnormally high 102 expression levels in the 1 stratum moleculare and 3 stratum polymorphum subregions of 2‐month‐old / 1 mice, but low 102 levels in the and 3 subregions of 7‐month‐old / 1 mice, reflecting the subregion‐specific reactivity and vulnerability of mouse models in different disease stages. Our findings provide fundamental data to support the functional differences of 102 in different hippocampal subregions during postnatal periods and may serve as the basis for additional functional studies on 102 in normal physiological conditions and different stages of .