Abstract
AimsSemaphorin7A (Sema7A) plays an important role in the immunoregulation of the brain. In our study, we aimed to investigate the expression patterns of Sema7A in epilepsy and further explore the roles of Sema7A in the regulation of seizure activity and the inflammatory response in PTZ‐kindled epileptic rats.MethodsFirst, we measured the Sema7A expression levels in patients with temporal lobe epilepsy (TLE) and in rats of a PTZ‐kindled epilepsy rat model. Second, to explore the role of Sema7A in the regulation of seizure activity, we conducted epilepsy‐related behavioral experiments after knockdown and overexpression of Sema7A in the rat hippocampal dentate gyrus (DG). Possible Sema7A‐related brain immune regulators (eg, ERK phosphorylation, IL‐6, and TNF‐α) were also investigated. Additionally, the growth of mossy fibers was visualized by anterograde tracing using injections of biotinylated dextran amine (BDA) into the DG region.ResultsSema7A expression was markedly upregulated in the brain tissues of TLE patients and rats of the epileptic model after PTZ kindling. After knockdown of Sema7A, seizure activity was suppressed based on the latency to the first epileptic seizure, number of seizures, and duration of seizures. Conversely, overexpression of Sema7A promoted seizures. Overexpression of Sema7A increased the expression levels of the inflammatory cytokines, IL‐6 and TNF‐α, ERK phosphorylation, and growth of mossy fibers in PTZ‐kindled epileptic rats.ConclusionSema7A is upregulated in the epileptic brain and plays a potential role in the regulation of seizure activity in PTZ‐kindled epileptic rats, which may be related to neuroinflammation. Sema7A promotes the inflammatory cytokines TNF‐α and IL‐6 as well as the growth of mossy fibers through the ERK pathway, suggesting that Sema7A may promote seizures by increasing neuroinflammation and activating pathological neural circuits. Sema7A plays a critical role in epilepsy and could be a potential therapeutic target for this neurological disorder.
Highlights
Epilepsy, currently one of the most common chronic neurological disorders, is characterized by persistent brain susceptibility to gen‐ erating epileptic seizures
We examined the changes in the inflammatory cytokines IL‐6 and tumor necrosis factor (TNF)‐α after U0126
Sema7A localizes to the cytomembrane and cytoplasm of neuronal subsets in the hippocampus and tempo‐ ral neocortex
Summary
Currently one of the most common chronic neurological disorders, is characterized by persistent brain susceptibility to gen‐ erating epileptic seizures. Numerous studies have suggested that the immune system and inflammatory processes in the central nervous system (CNS) may be important mechanisms involved in the pathophysiol‐ ogy of epilepsy and seizures.[6,7,8] Downstream inflammatory cytokines such as interleukin IL‐1β, IL‐6, tumor necrosis factor (TNF)‐α, and prostaglandin E2 (PGE2), as well as some inflammatory mediators in‐ cluding nuclear factor kappa B (NF‐κB) and cyclooxygenase (COX)‐2, are activated in the progression of seizures.[9] In the PTZ‐kindled epi‐ leptic rat model, increased expression levels of IL‐6 and TNF‐α were found.[10,11,12] Epileptic seizures induce the release of IL‐6 and TNF‐α cytokines from glial cells, likely increasing neuronal cell loss, enhanc‐ ing extraneuronal glutamate concentrations, and decreasing K+ and glutamate uptake by glia Such inflammatory responses cause hyper‐ excitability of neurons and recurrent seizures, eventually leading to the development of refractory epilepsy.[13,14,15,16] the mito‐ gen‐activated protein kinase (MAPK) signaling pathway is known to play an important role in epilepsy. The mechanism under‐ lying Sema7A‐related inflammation in epilepsy was explored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
