Sema7A, a brain immune regulator, regulates seizure activity in PTZ‐kindled epileptic rats

Deng, Jing; Xu, Tao; Yang, Juan; Zhang, Ke-Ming; Li, Qi; Yu, Xin-Yuan; Li, Rong; Fu, Jie; Jiang, Qian; Ma, Jue; Chen, Yangmei

doi:10.1111/cns.13181

Cited by 9 publications

(4 citation statements)

References 62 publications

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“…Our experiments showed changes in the number of bers crossing over the midline of the corpus callosum. [37,38]. The results of Golgi-Cox staining were evaluated by Sholl analysis by counting the number of intersections between concentric circles and dendrites to determine dendritic complexity and skeletonize dendritic spines to observe the number of changes [39,40].…”

Section: Discussionmentioning

confidence: 99%

Enriched environment promotes neuroplasticity by regulating the ALK5/Smad2/3/Gadd45β signaling pathway in rats with cerebral ischemia/reperfusion injury

Liu

Xie

et al. 2023

Preprint

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Background/Aims Enriched environment (EE) has been shown to modulate neuroplasticity in neurodegenerative diseases, but its role and mechanisms in ischemic stroke remain unclear. Our previous findings revealed that EE can promote cerebral activin receptor-like kinase 5 (ALK5) expression after cerebral ischemia/reperfusion (I/R). It was found that ALK5 might play a role in neuroplasticity through the modulation of Smad2/3/Growth Arrest DNA Damage 45 β (Gadd45β). Therefore, the present study aimed to explore the role of EE on neuroplasticity after cerebral ischemia/reperfusion and its mechanisms. Methods The middle cerebral artery occlusion/reperfusion (MCAO/R) method was employed to establish a rat model of cerebral ischemia/reperfusion injury. The role of ALK5 was determined by intracerebral stereotactic injection of adeno-associated virus (AAV) to inhibit the expression of ALK5. The respective effects of EE treatment with or without ALK5 knockdown on ALK5/Smad2/3/Gadd45β expression, infarct volume, newborn neurons, dendritic complexity and regenerated nerve fibers in rats were observed. Results Cerebral I/R injury induced an increase in ALK5 expression, Smad2/3 phosphorylation ratio, and Gadd45β expression for up to 14 days. EE treatment further enhanced the expression of these molecules, which was reversed by ALK5 knockdown. The protective effect of EE treatment on brain infarct volume, neurological function, newborn neurons, dendritic complexity, and nerve fiber regeneration following I/R injury were counteracted by the AAV-ALK5-induced knockdown of ALK5. Conclusion EE treatment can enhance neuroplasticity following cerebral ischemia/reperfusion injury, which was mediated by the regulation of ALK5/Smad2/3/Gadd45β signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Enriched environment promotes neuroplasticity by regulating the ALK5/Smad2/3/Gadd45β signaling pathway in rats with cerebral ischemia/reperfusion injury

Liu

Xie

et al. 2023

Preprint

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“…Kindling‐induced seizures are associated with activation of pro‐inflammatory pathways 40 and growth of mossy fibers, 41 which are known to contribute to epileptogenesis. However, the causal role of the DR 5‐HTergic neurons in kindling model of TLE is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of hyperactivity of the dorsal raphe 5‐HTergic neurons ameliorates hippocampal seizure

Cheng

Lai

et al. 2021

CNS Neurosci Ther

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Aims Epilepsy, frequently comorbid with depression, easily develops drug resistance. Here, we investigated how dorsal raphe (DR) and its 5‐HTergic neurons are implicated in epilepsy. Methods In mouse hippocampal kindling model, using immunochemistry, calcium fiber photometry, and optogenetics, we investigated the causal role of DR 5‐HTergic neurons in seizure of temporal lobe epilepsy (TLE). Further, deep brain stimulation (DBS) of the DR with different frequencies was applied to test its effect on hippocampal seizure and depressive‐like behavior. Results Number of c‐fos+ neurons in the DR and calcium activities of DR 5‐HTergic neurons were both increased during kindling‐induced hippocampal seizures. Optogenetic inhibition, but not activation, of DR 5‐HTergic neurons conspicuously retarded seizure acquisition specially during the late period. For clinical translation, 1‐Hz‐specific, but not 20‐Hz or 100‐Hz, DBS of the DR retarded the acquisition of hippocampal seizure. This therapeutic effect may be mediated by the inhibition of DR 5‐HTergic neurons, as optogenetic activation of DR 5‐HTergic neurons reversed the anti‐seizure effects of 1‐Hz DR DBS. However, DBS treatment had no effect on depressive‐like behavior. Conclusion Inhibition of hyperactivity of DR 5‐HTergic neuron may present promising anti‐seizure effect and the DR may be a potential DBS target for the therapy of TLE.

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“…A recent study identified SEMA7A as a critical cue that restricts serotonergic innervation in the spinal cord [ 23 ]. In PTZ-kindled epileptic rats, Sema7A was upregulated in the epileptic brain and played a potential role in the regulation of seizure activity [ 24 ]. SEMA5A ( semaphorin 5A ), another gene of the semaphorin family, was identified to be an ASD-associated gene, and there was evidence of decreased expression of this gene in patients with autism [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular and phenotypic characteristics of 15q24 microdeletion in pediatric patients with developmental disorders

et al. 2021

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Chromosome 15q24 microdeletion is a rare genetic disorder characterized by development delay, facial dysmorphism, congenital malformations, and occasional autism spectrum disorder (ASD). In this study, we identified five cases of 15q24 microdeletion using multiplex ligation-dependent probe amplification (MLPA) technology in a cohort of patients with developmental delay and/or intellectual disability. Two of these five cases had deletions that overlapped with the previously defined 1.1 Mb region observed in most reported cases. Two cases had smaller deletions (< 0.57 Mb) in the 15q24.1 low copy repeat (LCR) B-C region. They presented significant neurobehavioral features, suggesting that this smaller interval is critical for core phenotypes of 15q24 microdeletion syndrome. One case had minimal homozygous deletion of less than 0.11 Mb in the 15q24.1 LCR B-C region, which contained CYP1A1 (cytochrome P450 family 1 subfamily A member 1) and EDC3 (enhancer of mRNA decapping 3) genes, resulting in poor immunity, severe laryngeal stridor, and lower limbs swelling. This study provides additional evidence of 15q24 microdeletion syndrome with genetic and clinical findings. The results will be of significance to pediatricians in their daily practice.

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Sema7A, a brain immune regulator, regulates seizure activity in PTZ‐kindled epileptic rats

Cited by 9 publications

References 62 publications

Enriched environment promotes neuroplasticity by regulating the ALK5/Smad2/3/Gadd45β signaling pathway in rats with cerebral ischemia/reperfusion injury

Enriched environment promotes neuroplasticity by regulating the ALK5/Smad2/3/Gadd45β signaling pathway in rats with cerebral ischemia/reperfusion injury

Inhibition of hyperactivity of the dorsal raphe 5‐HTergic neurons ameliorates hippocampal seizure

Molecular and phenotypic characteristics of 15q24 microdeletion in pediatric patients with developmental disorders

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