Ethanol-induced neurodegeneration in NRSF/REST neuronal conditional knockout mice

Cai, Lei; Bian, Minjuan; Liu, M; Sheng, Zhao; Suo, Haiyun; Wang, Z; Huang, Fang; Fei, J

doi:10.1016/j.neuroscience.2011.02.059

Cited by 30 publications

(29 citation statements)

References 41 publications

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“…This result suggests that NRSF and REST4 are differentially regulated in PTZ-induced seizure, which is consistent with reports by Spencer [19]. Moreover, REST4 was more tightly regulated than NRSF, which confirms previous findings in other epilepsy model [11,13,19]. These findings demonstrate that NRSF and REST4 are of great importance in the development of PTZ-induced seizure.…”

Section: Neuronal Conditional Deletion Of Nrsf-alleviated Epileptiforsupporting

confidence: 92%

“…The efficiency and specificity of NRSF deletion in the brains of NRSF cKO mice have been confirmed in our previous work [13]. NRSF cKO mice could survive into adulthood with normal body weight, locomotor activity (data not shown).…”

Section: Resultssupporting

confidence: 71%

“…Neuronal conditional knockout of NRSF decreased vulnerability to seizures induced by PTZ in mice To investigate whether NRSF functions in the development of PTZ-induced seizure activity, in the present study, NRSF cKO mice were adopted, in which NRSF gene was conditionally knocked out in the neurons (see 'Materials and Methods' section) [13]. The efficiency and specificity of NRSF deletion in the brains of NRSF cKO mice have been confirmed in our previous work [13].…”

Section: Resultssupporting

confidence: 53%

“…Animals NRSF/REST neuronal cKO mice (NRSF cKO) were generated in our laboratory by crossing NRSF flox/flox mice (in which two loxP elements were introduced into the mouse genome flanking exon 2 of the NRSF locus) with neuronspecific enolase (NSE)-Cre transgenic mice (hereafter referred to as 'Cre', in which Cre recombinase is expressed exclusively in neurons) [13]. NSE-Cre mice served as controls.…”

Section: Methodsmentioning

confidence: 99%

“…Increasing evidence suggested that the expressions of neuronal-specific genes in epilepsy, such as BDNF (brain-derived neurotrophic factor), GluR2, and PPT-A ( preprotachykinin-A gene), are regulated by NRSF and REST4, indicating their important roles in epileptogenesis [10,13,19]. In mice, targeted mutation of NRSF caused embryonic lethality, and thus cannot be used to study NRSF function in postnatal stages [22].…”

Section: Introductionmentioning

confidence: 99%

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Neuronal conditional knockout of <italic>NRSF</italic> decreases vulnerability to seizures induced by pentylenetetrazol in mice

Liu¹,

Sheng²,

Cai³

et al. 2012

ABBS

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Neuron restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor, has been reported to modulate neuronal excitability and acts as endogenous anticonvulsant in kainic acid-induced or kindling-evoked seizure activity. However, whether NRSF functions in pentylenetetrazol (PTZ)-induced seizure activity has never been studied. To investigate the role of endogenous NRSF in the epileptogenesis induced by PTZ, in our experiment, NRSF neuronal conditional knockout mice (NRSF cKO) were adopted, in which NRSF was specifically deleted in neurons by the Cre-loxP system. Seizure threshold for PTZ, including the dose-response convulsions and the threshold dose, was compared between NRSF cKO and control mice. The threshold dose of PTZ that induced clonic and tonic seizures was significantly higher in NRSF cKO mice compared with the control. Similarly, the median lethal dose (LD 50 ) of PTZ in NRSF cKO mice was also considerably higher than that of the control mice. These results revealed that NRSF cKO mice are of higher resistance to convulsions induced by PTZ. Our work first demonstrated the function of NRSF in PTZ-induced seizure and provided new evidence for differential pathways in diverse types of seizure.

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Section: Neuronal Conditional Deletion Of Nrsf-alleviated Epileptiforsupporting

confidence: 92%

Section: Resultssupporting

confidence: 71%

Section: Resultssupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neuronal conditional knockout of <italic>NRSF</italic> decreases vulnerability to seizures induced by pentylenetetrazol in mice

Liu¹,

Sheng²,

Cai³

et al. 2012

ABBS

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show abstract

Splicing factor NSSR1 reduces neuronal injury after mouse transient global cerebral ischemia

Yao

Cui

et al. 2015

Glia

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This study focuses on the function of NSSR1, a splicing factor, in neuronal injury in the ischemic mouse brain using the transient global cerebral ischemic mouse model and the cultured cells treated with oxygen-glucose deprivation (OGD). The results showed that the cerebral ischemia triggers the expression of NSSR1 in hippocampal astrocytes, predominantly the dephosphorylated NSSR1 proteins, and the Exon3 inclusive NCAM-L1 variant and the Exon4 inclusive CREB variant. While in the hippocampus of astrocyte-specific NSSR1 conditional knockdown (cKD) mice, where cerebral ischemia no longer triggers NSSR1 expression in astrocytes, the expression of Exon3 inclusive NCAM-L1 variant and Exon4 inclusive CREB variant were no longer triggered as well. In addition, the injury of hippocampal neurons was more severe in astrocyte-specific NSSR1 cKD mice compared with in wild-type mice after brain ischemia. Of note, the culture media harvested from the astrocytes with overexpression of NSSR1 or the Exon3 inclusive NCAM-L1 variant, or Exon4 inclusive CREB variant were all able to reduce the neuronal injury induced by OGD. The results provide the evidence demonstrating that: (1) Splicing factor NSSR1 is a new factor involved in reducing ischemic injury. (2) Ischemia induces NSSR1 expression in astrocytes, not in neurons. (3) NSSR1-mediated pathway in astrocytes is required for reducing ischemic neuronal injury. (4) NCAM-L1 and CREB are probably mediators in NSSR1-mediated pathway. In conclusion, our results suggest for the first time that NSSR1 may provide a novel mechanism for reducing neuronal injury after ischemia, probably through regulation on alternative splicing of NCAM-L1 and CREB in astrocytes.

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NRSF deficiency leads to abnormal postnatal development of dentate gyrus and impairment of progenitors in subgranular zone of hippocampus

et al. 2021

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Neuron‐restrictive silencing factor (NRSF) is a zinc‐finger transcription factor that regulates expression of a diverse set of genes. However, NRSF function in brain development still remains elusive. In the present study, we generated NRSF‐conditional knockout (NRSF‐cKO) mice by hGFAP‐Cre/loxp system to study the effect of NRSF deficiency on brain development. Results showed that NRSF conditional knockout caused a smaller hippocampus and a thinner granule cell layer (GCL) in mice. Moreover, the reduction and disarrangement of GFAP+ cells in subgranular zone (SGZ) of NRSF‐cKO mice was accompanied with the decreased number of premature neurons, neural stem cells (NSCs) and neural progenitor cells (NPCs), as well as compromising the majority of mitotically active cells. The analysis of postnatal development of hippocampus indicated the existence of an abnormality at postnatal day (P) 8, rather than at P1, in NRSF‐cKO mice, although the densities of Ki67+ cells with mitotic ability in dentate gyrus were relatively unaffected at P1 and P8. Meanwhile, NRSF deficiency led to abnormal organization of SGZ at P8 during postnatal development. RNA‐Seq analysis revealed 79 deregulated genes in hippocampus of NRSF‐cKO mice at P8, which were involved in p53 signal transduction, neuron migration and negative regulation of cell proliferation, etc. The deregulation of p53 pathway in NRSF‐cKO mice at P1 and P8 was evidenced, of which p21/Cdkn1a was accumulated in a portion of NSCs and NPCs in hippocampus during postnatal development. Together, these results, for the first time, revealed that NRSF could significantly influence the postnatal development of hippocampus, especially the formation of SGZ.

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Ethanol-induced neurodegeneration in NRSF/REST neuronal conditional knockout mice

Cited by 30 publications

References 41 publications

Neuronal conditional knockout of <italic>NRSF</italic> decreases vulnerability to seizures induced by pentylenetetrazol in mice

Neuronal conditional knockout of <italic>NRSF</italic> decreases vulnerability to seizures induced by pentylenetetrazol in mice

Splicing factor NSSR1 reduces neuronal injury after mouse transient global cerebral ischemia

NRSF deficiency leads to abnormal postnatal development of dentate gyrus and impairment of progenitors in subgranular zone of hippocampus

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Ethanol-induced neurodegeneration in NRSF/REST neuronal conditional knockout mice

Cited by 30 publications

References 41 publications

Neuronal conditional knockout of &lt;italic&gt;NRSF&lt;/italic&gt; decreases vulnerability to seizures induced by pentylenetetrazol in mice

Neuronal conditional knockout of &lt;italic&gt;NRSF&lt;/italic&gt; decreases vulnerability to seizures induced by pentylenetetrazol in mice

Splicing factor NSSR1 reduces neuronal injury after mouse transient global cerebral ischemia

NRSF deficiency leads to abnormal postnatal development of dentate gyrus and impairment of progenitors in subgranular zone of hippocampus

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Resources

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Neuronal conditional knockout of <italic>NRSF</italic> decreases vulnerability to seizures induced by pentylenetetrazol in mice

Neuronal conditional knockout of <italic>NRSF</italic> decreases vulnerability to seizures induced by pentylenetetrazol in mice