Loss of NB-3 Aggravates Cerebral Ischemia by Impairing Neuron Survival and Neurite Growth

Huang, Xin; Sun, Jia; Zhao, Tong; Wu, Kui-Wu; Watanabe, Kazutada; Xiao, Zhi‐Cheng; Zhu, Lijing; Fan, Ming

doi:10.1161/strokeaha.110.609560

Cited by 17 publications

(22 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the mRNA microarray data showed similar results to those from rodent ischemic stroke models (middle cerebral artery occlusion, MCAo), indicating our in vitro model of ischemic injury is reflective of the gene expression changes taking place in an in vivo ischemic injury model [15]. Our observations on the inverse regulation of genes crucial to neuronal function upon ischemic injury are hence consistent with previous reports [15], [18].…”

Section: Discussionsupporting

confidence: 90%

“…An inverse expression of these genes ( Axin2 , Prkcb , Cntn1 , Ncam1 , Negr1 , Nrxn1 , Sh2b3 ) was observed upon ischemic insult (Table 3). Similarly, NB-3 , a cell adhesion molecule expressed in neurons for axonal extension and neuronal survival, has been reported to be inversely regulated during ischemic injury, resulting in impaired neuronal survival and neurite outgrowth [18]. Moreover, the mRNA microarray data showed similar results to those from rodent ischemic stroke models (middle cerebral artery occlusion, MCAo), indicating our in vitro model of ischemic injury is reflective of the gene expression changes taking place in an in vivo ischemic injury model [15].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, the expression of genes essential to axonal extension and neuronal survival, such as the cell adhesion molecule NB-3 , is inversely regulated during ischemic injury, resulting in impaired neuronal survival and neurite outgrowth [18]. Moreover, modulation of certain miRNAs has been shown to confer neuroprotection in cerebral ischemic models [19]–[21].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression Profiling of RNA Transcripts during Neuronal Maturation and Ischemic Injury

et al. 2014

View full text Add to dashboard Cite

Neuronal development is a pro-survival process that involves neurite growth, synaptogenesis, synaptic and neuronal pruning. During development, these processes can be controlled by temporal gene expression that is orchestrated by both long non-coding RNAs and microRNAs. To examine the interplay between these different components of the transcriptome during neuronal differentiation, we carried out mRNA, long non-coding RNA and microRNA expression profiling on maturing primary neurons. Subsequent gene ontology analysis revealed regulation of axonogenesis and dendritogenesis processes by these differentially expressed mRNAs and non-coding RNAs. Temporally regulated mRNAs and their associated long non-coding RNAs were significantly over-represented in proliferation and differentiation associated signalling, cell adhesion and neurotrophin signalling pathways. Verification of expression of the Axin2, Prkcb, Cntn1, Ncam1, Negr1, Nrxn1 and Sh2b3 mRNAs and their respective long non-coding RNAs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile to the maturation process, thus suggesting their role(s) in maintaining neuronal structure and function. Furthermore, we propose that expression of the cell adhesion molecules, Ncam1 and Negr1 might be tightly regulated by both long non-coding RNAs and microRNAs.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression Profiling of RNA Transcripts during Neuronal Maturation and Ischemic Injury

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The notion that Cntn6 plays a role in neuronal survival was previously demonstrated by the increased amount of apoptosis in granule cells of the cerebellum and in primary cultures derived from Cntn6 ¡/¡ mouse cortex. 18,20 A selective role of Cntn6 in interneuron function was derived from the observation that the number of PVC interneurons was significantly decreased in Cntn6 ¡/¡ mice, while the number of NPYC interneurons remained unchanged. Cntn6 may serve as a ligand for receptors on PVC interneurons and thereby contribute to migration, guidance or survival or other functions of these interneurons in the visual cortex.…”

Section: Discussionmentioning

confidence: 99%

“…17 Cntn6 was previously found to regulate neurite outgrowth in vitro, 19 and this property was reflected by the delayed formation of the corticospinal tract in Cntn6 ¡/¡ mice. 20,21 These known neurobiological processes exerted by Cntn6 can be attributed to the cell adhesion properties of Cntn6.…”

Section: Introductionmentioning

confidence: 99%

Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus

Zuko

Oguro-Ando

et al. 2016

Cell Adhesion & Migration

View full text Add to dashboard Cite

The gene encoding the neural cell adhesion molecule Contactin-6 (Cntn6 a.k.a. NB-3) has been implicated as an autism risk gene, suggesting that its mutation is deleterious to brain development. Due to its GPI-anchor at Cntn6 may exert cell adhesion/receptor functions in complex with other membrane proteins, or serve as a ligand. We aimed to uncover novel phenotypes related to Cntn6 functions during development in the cerebral cortex of adult Cntn6 ¡/¡ mice. We first determined Cntn6 protein and mRNA expression in the cortex, thalamic nuclei and the hippocampus at P14, which decreased specifically in the cortex at adult stages. Neuroanatomical analysis demonstrated a significant decrease of Cux1C projection neurons in layers II-IV and an increase of FoxP2C projection neurons in layer VI in the visual cortex of adult Cntn6 ¡/¡ mice compared to wild-type controls. Furthermore, the number of parvalbuminC (PV) interneurons was decreased in Cntn6 ¡/¡ mice, while the amount of NPYC interneurons remained unchanged. In the hippocampus the delineation and outgrowth of mossy fibers remained largely unchanged, except for the observation of a larger suprapyramidal bundle. The observed abnormalities in the cerebral cortex and hippocampus of Cntn6 ¡/¡ mice suggests that Cntn6 serves developmental functions involving cell survival, migration and fasciculation. Furthermore, these data suggest that Cntn6 engages in both trans-and cis-interactions and may be involved in larger protein interaction networks.

show abstract

Contactin‐6‐deficient male mice exhibit the abnormal function of the accessory olfactory system and impaired reproductive behavior

et al. 2023

Self Cite

View full text Add to dashboard Cite

Introduction Contactin‐6 (CNTN6), also known as NB‐3, is a neural recognition molecule and a member of the contactin subgroup of the immunoglobulin superfamily. Gene encoding CNTN6 is expressed in many regions of the neural system, including the accessory olfactory bulb (AOB) in mice. We aim to determine the effect of CNTN6 deficiency on the function of the accessory olfactory system (AOS). Methods We examined the effect of CNTN6 deficiency on the reproductive behavior of male mice through behavioral experiments such as urine sniffing and mate preference tests. Staining and electron microscopy were used to observe the gross structure and the circuitry activity of the AOS. Results Cntn6 is highly expressed in the vomeronasal organ (VNO) and the AOB, and sparsely expressed in the medial amygdala (MeA) and the medial preoptic area (MPOA), which receive direct and/or indirect projections from the AOB. Behavioral tests to examine reproductive function in mice, which is mostly controlled by the AOS, revealed that Cntn6 −/− adult male mice showed less interest and reduced mating attempts toward estrous female mice in comparison with their Cntn6 +/+ littermates. Although Cntn6 −/− adult male mice displayed no obvious changes in the gross structure of the VNO or AOB, we observed the increased activation of granule cells in the AOB and the lower activation of neurons in the MeA and the MPOA as compared with Cntn6 +/+ adult male mice. Moreover, there were an increased number of synapses between mitral cells and granule cells in the AOB of Cntn6 −/− adult male mice as compared with wild‐type controls. Conclusion These results indicate that CNTN6 deficiency affects the reproductive behavior of male mice, suggesting that CNTN6 participated in normal function of the AOS and its ablation was involved in synapse formation between mitral and granule cells in the AOB, rather than affecting the gross structure of the AOS.

show abstract

Loss of NB-3 Aggravates Cerebral Ischemia by Impairing Neuron Survival and Neurite Growth

Cited by 17 publications

References 19 publications

Expression Profiling of RNA Transcripts during Neuronal Maturation and Ischemic Injury

Expression Profiling of RNA Transcripts during Neuronal Maturation and Ischemic Injury

Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus

Contactin‐6‐deficient male mice exhibit the abnormal function of the accessory olfactory system and impaired reproductive behavior

Contact Info

Product

Resources

About