Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

OBJECTIVETo investigate the molecular mechanism of nectin-like molecule 1 (NECL1) inhibiting the migration and invasion of U251 glioma cells.

METHODSWe infected U251 glioma cells with adeno-nectin-like molecule 1 (Ad-NECL1) or empty adenovirus (Ad). Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells. DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines. The differential expression of osteopontin (OPN), a gene related to migration and invasion, was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry.

RESULTSThe restoration of NECL1 inhibited migration of U251 cells significantly (P<0.05). Altogether 195 genes were found differentially expressed by microarray, in which 175 were up-regulated and 20 down-regulated, including 9 extracellular matrix proteins involved in the migration of cells. Both mRNA and protein expressions of OPN, the most markedly reduced extracellular matrix protein, were found decreased in U251 cells after restoration of NECL1. Immunohistochemical assay also detected an increase of OPN in glioma tissues, related with the progressing of malignant grade.

CONCLUSIONA link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.

Brain Neoplasms ; metabolism ; pathology ; Cell Adhesion Molecules ; physiology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; physiology ; Glioma ; metabolism ; pathology ; Humans ; Nectins ; Neoplasm Invasiveness ; physiopathology ; Neoplasm Metastasis ; physiopathology ; Osteopontin ; genetics

OBJECTIVETo study the relationship of nonsyndromic cleft lip and/or palate (NSCL/P) and poliovirus receptor-related 1 exon3 (PVRL1exon3) polymorphisms in Han People of Jiangzhe area.

METHODSPVRL1exon3 was examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique in the 50 patients with NSCL/P and 85 healthy parents.

RESULTSNo W185X mutation was found in the PVRL1exon 3.

CONCLUSIONIt indicates that there is no relationship between NSCL/P and PVRL1exon3 in Han People in Jiangzhe area.

Asian Continental Ancestry Group ; genetics ; Cell Adhesion Molecules ; genetics ; Child, Preschool ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Exons ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Male ; Nectins ; Pedigree ; Polymorphism, Genetic ; Receptors, Virus ; genetics