N-Formyl-Methionyl-Leucyl-Phenylalanine Plays a Neuroprotective and Anticonvulsant Role in Status Epilepticus Model.

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-09-24 DOI:10.1007/s10571-023-01410-z
Igor Santana de Melo, Robinson Sabino-Silva, Maisa Araújo Costa, Emília Rezende Vaz, Cassius Iury Anselmo-E-Silva, Thainá de Paula Soares Mendonça, Kellysson Bruno Oliveira, Fernanda Maria Araújo de Souza, Yngrid Mickaelli Oliveira Dos Santos, Amanda Larissa Dias Pacheco, Jucilene Freitas-Santos, Douglas Carvalho Caixeta, Luiz Ricardo Goulart, Olagide Wagner de Castro
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Abstract

Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis. N-formyl peptide receptor (FPR) has been associated with inflammatory process. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/μL, 1 μL) followed by fMLP (1 mg/mL, 1 μL) or vehicle (VEH, saline 0.9%, 1 μL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine's Scale. After 24 h of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. However, our results showed that the intrahippocampal infusion of fMLP reduced the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together, our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy. Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).

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N-甲酰-甲酰-亮氨酸-苯丙氨酸在癫痫模型中起神经保护和抗惊厥作用。
癫痫持续状态(SE)被描述为持续和自我维持的癫痫发作,它会引发海马神经退行性变、炎症和胶质增生。N-甲酰基肽受体(FPR)与炎症过程有关。N-甲酰基-甲酰基-亮氨酸-苯丙氨酸(fMLP)肽通过激活G蛋白偶联的FPR发挥抗炎作用。在这里,我们评估了fMLP肽对边缘癫痫发作、记忆巩固和海马神经退行性变过程的影响。雄性Wistar大鼠(褐家鼠)在海马微量注射毛果芸香碱(H-PILO,1.2 mg/mL,1μL),然后注射fMLP(1 mg/mL,2μL)或赋形剂(VEH,0.9%生理盐水,1μL)。在SE的90分钟内,根据拉辛量表对癫痫发作进行分析。SE 24小时后,通过抑制性回避测试评估记忆损伤,并评估海马区的神经退行性变过程。fMLP给药后,湿狗奶昔(WDS)的潜伏期和次数没有变化。然而,我们的研究结果表明,海马内输注fMLP可以降低癫痫发作的严重程度以及边缘癫痫发作的次数。此外,fMLP输注保护了SE后的记忆功能障碍。最后,海马内给予fMLP减轻了两个海马的神经退行性变过程。总之,我们的数据对fMLP肽的功能作用提出了新的见解,对其作为治疗癫痫等脑疾病的治疗剂的潜在用途具有重要意义。fMLP在癫痫持续状态中的神经保护和抗惊厥作用示意图。最初,在海马体中植入套管,并向海马体中给予毛果芸香碱/生理盐水,然后给予fMLP/生理盐水(a-C)。fMLP降低了癫痫发作的严重程度和海马神经元的死亡,并防止了记忆缺陷(D)。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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