Neuroligin Expressed in Nonneuronal Cells Triggers Presynaptic Development in Contacting Axons

Scheiffele, Peter; Fan, Jinhong; Choih, Jenny; Fetter, Richard D.; Serafini, Tito

doi:10.1016/s0092-8674(00)80877-6

Cited by 1,105 publications

(1,143 citation statements)

References 42 publications

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“…The postsynaptic Nlgns form heterophilic connections with Nrxns and are thus important for synapse formation and cognitive functions (Dean and Dresbach 2006). These proteins even induce the differentiation of presynaptic and postsynaptic specialization respectively in adjoining nonneuronal cells (Scheiffele et al 2000;Graf et al 2004). Moreover, their interaction is involved in neuronal plasticity mechanism and neuronal disorders such as autism (Südhof 2008).…”

Section: Discussionmentioning

confidence: 99%

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

Kumar

Thakur

2015

AGE

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Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed. In the present study, we have examined the age-related changes in the expression of these proteins in cerebral cortex and hippocampus of 10-, 30-, 50-, and 80-week-old male mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis indicated that messenger RNA (mRNA) level of Nrxn1 and Nlgn3 significantly increased from 10 to 30 weeks and then decreased at 50 weeks in both the regions. However, in 80-week-old mice, Nrxn1 and Nlgn3 were further downregulated in cerebral cortex while Nrxn1 was downregulated and Nlgn3 was upregulated in hippocampus. These findings were corroborated by immunoblotting and immunofluorescence results. When the expression of Nrxn1 and Nlgn3 was correlated with presynaptic density marker synaptophysin, it was found that synaptophysin protein expression in cerebral cortex was high at 10 weeks and decreased gradually up to 80 weeks, whereas in hippocampus, it decreased until 50 weeks and then increased remarkably at 80 weeks. Furthermore, Pearson's correlation analysis showed that synaptophysin had a strong relation with Nrxn1 and Nlgn3 in cerebral cortex and with Nlgn3 in hippocampus. Thus, these findings showed that Nrxn1 and Nlgn3 are differentially expressed in cerebral cortex and hippocampus which might be responsible for alterations in synaptic plasticity during aging.

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Section: Discussionmentioning

confidence: 99%

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

Kumar

Thakur

2015

AGE

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“…In support of the former possibility, however, it has been shown that postsynaptic proteins can induce presynaptic assembly and drive the formation of new presynaptic contacts (Biederer et al, 2002;Scheiffele et al, 2000). Furthermore, the postsynaptic scaffolding protein PSD95, along with its interaction partners, can modulate the release probability of presynaptic transmitter vesicles in a retrograde manner (Futai et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

Giovanoli

Weber‐Stadlbauer

Schedlowski

et al. 2016

Brain, Behavior, and Immunity

126

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Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre-and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced an adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1 levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation. AbstractPrenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre--and postsynaptic deficits.Using a well--established mouse model of maternal exposure to the viral mimetic polyriboinosinic--polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)--exposed and control mothers. We found that prenatal immune activation induced adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early--life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial a...

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“…Although different works suggested their involvement in synapses formation (Scheiffele et al, 2000;Dean et al, 2003;Graf et al, 2004;Prange et al, 2004;Chubykin et al, 2005;Levinson et al, 2005), other studies and the analysis of knockout mice proposed that Neuroligins, along with the alphaforms of Neurexins, are involved in synaptic function and maturation (Missler et al, 2003;Sara et al, 2005;Varoqueaux et al, 2006;Chubykin et al, 2007). Triple knockout mice lacking Nlgn1-3 die shortly after birth and present normal synapse numbers with an apparently normal ultrastructure (Varoqueaux et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the neuroligin gene family expression and evolution in zebrafish

Rissone¹,

Sangiorgio²,

Monopoli³

et al. 2010

Developmental Dynamics

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Neuroligins constitute a family of transmembrane proteins localized at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. They are involved in synaptic function and maturation and recent studies have linked mutations in specific human Neuroligins to mental retardation and autism. We isolated the human Neuroligin homologs in Danio rerio. Next, we studied their gene structures and we reconstructed the evolution of the Neuroligin genes across vertebrate phyla. Using reverse-transcriptase polymerase chain reaction, we analyzed the expression and alternative splicing pattern of each gene during zebrafish embryonic development and in different adult organs. By in situ hybridization, we analyzed the temporal and spatial expression pattern during embryonic development and larval stages and we found that zebrafish Neuroligins are expressed throughout the nervous system. Globally, our results indicate that, during evolution, specific subfunctionalization events occurred within paralogous members of this gene family in zebrafish. Developmental Dynamics 239:688-702,

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Neuroligin Expressed in Nonneuronal Cells Triggers Presynaptic Development in Contacting Axons

Cited by 1,105 publications

References 42 publications

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

Characterization of the neuroligin gene family expression and evolution in zebrafish

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