利用紅藻胺酸引發抽搐之幼鼠來探討神經和細胞激素之表現

利用紅藻胺酸引發抽搐之幼鼠來探討神經和細胞激素之表現

 親皮質素釋放激素（ CRH ）是一種由 41 個胺基酸所組成的神經，它也是 下視丘 - 腦下垂體 - 腎上腺皮質軸線的主要調節者，可導致腦下垂體合成分泌 ACTH 進而刺激腎上腺皮質分泌醣皮質固醇。已經有文獻指出 CRH 在人類幼 年癲癇或幼鼠痙的發生扮演相當重要的角色。因而有學者提出「 CRH 過量 產生導致癲癇發生」之假說，另外，於幼鼠腦室注射 CRH 比起成鼠能更快地 引發痙。近年來許多研究發現細胞激素具有調節內分泌的功能，並參與許 多中樞神經系統疾病的過程進展，基於上述這些原因，為更能深入了解 CRH 在癲癇所參與的病理機轉，我們利用紅藻胺酸（ KA ）引發幼鼠產生抽搐藉以 探討 CRH 和細胞激素在周邊或腦中的表現情形。實驗結果指出：在注射 KA 的 P30 天幼鼠其血漿中 CRH 濃度（ 46.62±30.32 ng/ml, p=0.0303 ）明顯地較控 制組為高，然而在注射 KA 的 P7 天、 P14 天幼鼠其血漿中 CRH 濃度和控制組 相比卻無統計上的差異。在注射 DM 的 P30 天幼鼠其血漿中 CRH 濃度明顯地 較注射 KA 的幼鼠其血漿中 CRH 濃度為低。另一方面，利用 RT-PCR 方法來 探討神經 CRH 、 POMC ）和細胞激素（ IL-1β 、 IL-6 、 TNF-α 、 IF（ N-γ ）在不同腦區的 mRNA 表現情形。在注射 KA 的 P30 天幼鼠的大腦皮質其 CRH 、 IL-1β 、 IL-6 的表現明顯地比控制組為高；此外，在注射 KA 的 P7 天 幼鼠的大腦皮質其 CRH 的表現也明顯地比控制組為高。這些實驗結果顯示：

CRH 和細胞激素 IL-1β 、 IL-6 在幼鼠痙上可能具有免疫調節的功能。

The Expression of Neuropeptides and Cytokines in the Neonatal Rats with Kainate-Induced Seizure

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Corticotropin-Release Hormone (CRH), a 41 amino acid neuropeptide, is a major regulator of the HPA axis, which release leads to pituitary production of adrenocorticotropic hormone (AC TH) followed by glucocorticoid secretion by the adrenal cortex. CRH has been implicated as a n important neuro-hormone participating in seizure generation particularly in early life of both human and animals. It is possible that not only CRH presents as a pro-convulsant in the develo ping brain, but in seizure activity, it may elicit release of CRH which could further enhance th e seizure intensity. To address this issue we measured the plasma CRH concentration in devel oping rats received kainic acid (KA), a convulsant agent which exerts behavioral and electrop hysiological seizure activities by activating at kainate receptor and N-methyl-D-aspartate (NM DA) receptor. We also determine whether the NMDA receptor antagonist-dextromethorphan (DM) could attenuate release of CRH on KA-induced seizure on the release of CRH. These res ults demonstrated that significantly increase circulating CRH concentration (46.62±30.32 ng/

ml, p=0.0303) was observed in P30 rat but not on P7 and P14 rat. Injection of DM could effect

ively attenuate the KA-induced seizure intensity as well as the CRH level (p=0.0026) on P30 r

at. Furthermore, mRNA expression of neuropeptide (CRH and POMC) and cytokines (IL-6, I

L-1β, TNF-α, and IFN-γ) from different brain region are analyzed by RT-PCR. In P30 rat cort

ex, CRH, IL-6 and IL-lβ mRNA expression were significantly increased in KA-induced seizur

e as compared to control. In addition, CRH mRNA is also significantly increased in P7 rat cort

ex in KA-induced seizure as compared to control. These data support the CRH and cytokines

(IL-lβ and IL-6) may have immunoregulatory role in seizure activity.