Developmental expression of the neuroligins and neurexins in fragile X mice

Abstract

Neuroligins and neurexins are transsynaptic proteins involved in the maturation of glutamatergic and GABAergic synapses. Research has identified synaptic proteins and function as primary contributors to the development of fragile X syndrome. Fragile X mental retardation protein (FMRP), the protein that is lacking in fragile X syndrome, binds neuroligin-1 and -3 mRNA. Using in situ hybridization, we examined temporal and spatial expression patterns of neuroligin (NLGN) and neurexin (NRXN) mRNAs in the somatosensory (S1) cortex and hippocampus in wild-type (WT) and fragile X knockout (FMR1-KO) mice during the first 5 weeks of postnatal life. Genotype-based differences in expression included increased NLGN1 mRNA in CA1 and S1 cortex, decreased NLGN2 mRNA in CA1 and dentate gyrus (DG) regions of the hippocampus, and increased NRXN3 mRNA in CA1, DG, and S1 cortex between female WT and FMR1-KO mice. In male mice, decreased expression of NRXN3 mRNA was observed in CA1 and DG regions of FMR1-KO mice. Sex differences in hippocampal expression of NLGN2, NRXN1, NRXN2, and NRXN3 mRNAs and in S1 cortex expression of NRXN3 mRNAs were observed WT mice, whereas sex differences in NLGN3, NRXN1, NRXN2, and NRXN3 mRNA expression in the hippocampus and in NLGN1, NRXN2 and NRXN3 mRNA expression in S1 cortex were detected in FMR1-KO mice. These results provide a neuroanatomical map of NLGN and NRXN expression patterns over postnatal development in WT and FMR1-KO mice. The differences in developmental trajectory of these synaptic proteins could contribute to long-term differences in CNS wiring and synaptic function.

Reelin cells and sex‐dependent synaptopathology in autism following postnatal immune activation

“…While there was a transient early increase in females, LPS‐treated males demonstrated a long‐term decrease in expression of all three genes. These findings agree with previous studies that found decreased expression of NRXN3 mRNA in male fragile X knockout (FMR1‐KO) mice while expression was increased in females (Lai et al, 2016). NLGNs have a critical role in the balance of inhibitory and excitatory transmission, and mice with NLGN1 deletion exhibited repetitive stereotyped grooming behaviours (Blundell et al, 2010).…”

Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual disability, hyperphagia, and obesity

“…One intriguing possibility is that altered NLGN2 function may result in a sex‐specific phenotype. Sex differences in hippocampal NLGN2 expression have been observed in mice [Lai et al, ] and NLGN2 expression is regulated by 17‐beta‐estradiol and progesterone in rat uterine tissue [Kang et al, ]. Thus, altered NLGN2 function may affect males and females differently.…”

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

“…The dentate gyrus (DG) is a hippocampal subregion that plays a critical role in information processing including spatial memory ( Jonas and Lisman, 2014 ; Bott et al, 2016 ) and the aging-related functional alterations in this region were previously described for rats, mice, and other mammalian models ( Lister and Barnes, 2009 ). The results obtained from FMR1 KO mouse models indicate an important function of FMRP in physiology, structure and connectivity of DG, and the related behavior ( Bostrom et al, 2016 ; Lai et al, 2016 ; Scharkowski et al, 2017 ). Previous studies on rats showed deficits in hippocampal-dependent memory in a FMR1 KO model ( Till et al, 2015 ) and behavior-induced changes of FMRP level in DG ( Irwin et al, 2005 ).…”