Yuki Kajita, Yuki Fukuda, Riho Kawamatsu, Takanori Oyanagi, Hajime Mushiake
{"title":"戊四氮唑点燃诱导海马体视蛋白中间神经元中 GAD65 表达的动态变化","authors":"Yuki Kajita, Yuki Fukuda, Riho Kawamatsu, Takanori Oyanagi, Hajime Mushiake","doi":"10.1016/j.pbb.2024.173755","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>One of the mechanisms of epileptgenesis is impairment of inhibitory neural circuits. Several studies have compared neural changes among subtypes of gamma-aminobutyric acid-related (GABAergic) neurons after acquired epileptic seizure. However, it is unclear that GABAergic neural modifications that occur during acquisition process of epileptic seizure.</p></div><div><h3>Methods</h3><p>Male rats were injected with pentylenetetrazole (PTZ kindling: <em>n</em> = 30) or saline (control: <em>n</em> = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points.</p></div><div><h3>Results</h3><p>Bimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM<sup>+</sup>) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABA<sub>A</sub>R α1, GABA<sub>B</sub>R1, and VGAT cells showed no change following short- or long-term PTZ kindling.</p></div><div><h3>Conclusion</h3><p>PTZ kindling induces bimodal changes in the epileptic seizure stage. Seizure stage is transiently suppressed after short-term PTZ injection with GAD65 upregulation in SOM<sup>+</sup> cells. The seizure stage is progressed again after long-term PTZ injection with GAD65 reduction to baseline level.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091305724000492/pdfft?md5=6c78cab6dc46f83ad326c44c9c0333d3&pid=1-s2.0-S0091305724000492-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Pentylenetetrazole kindling induces dynamic changes in GAD65 expression in hippocampal somatostatin interneurons\",\"authors\":\"Yuki Kajita, Yuki Fukuda, Riho Kawamatsu, Takanori Oyanagi, Hajime Mushiake\",\"doi\":\"10.1016/j.pbb.2024.173755\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>One of the mechanisms of epileptgenesis is impairment of inhibitory neural circuits. Several studies have compared neural changes among subtypes of gamma-aminobutyric acid-related (GABAergic) neurons after acquired epileptic seizure. However, it is unclear that GABAergic neural modifications that occur during acquisition process of epileptic seizure.</p></div><div><h3>Methods</h3><p>Male rats were injected with pentylenetetrazole (PTZ kindling: <em>n</em> = 30) or saline (control: <em>n</em> = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points.</p></div><div><h3>Results</h3><p>Bimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM<sup>+</sup>) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABA<sub>A</sub>R α1, GABA<sub>B</sub>R1, and VGAT cells showed no change following short- or long-term PTZ kindling.</p></div><div><h3>Conclusion</h3><p>PTZ kindling induces bimodal changes in the epileptic seizure stage. 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Pentylenetetrazole kindling induces dynamic changes in GAD65 expression in hippocampal somatostatin interneurons
Introduction
One of the mechanisms of epileptgenesis is impairment of inhibitory neural circuits. Several studies have compared neural changes among subtypes of gamma-aminobutyric acid-related (GABAergic) neurons after acquired epileptic seizure. However, it is unclear that GABAergic neural modifications that occur during acquisition process of epileptic seizure.
Methods
Male rats were injected with pentylenetetrazole (PTZ kindling: n = 30) or saline (control: n = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points.
Results
Bimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM+) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABAAR α1, GABABR1, and VGAT cells showed no change following short- or long-term PTZ kindling.
Conclusion
PTZ kindling induces bimodal changes in the epileptic seizure stage. Seizure stage is transiently suppressed after short-term PTZ injection with GAD65 upregulation in SOM+ cells. The seizure stage is progressed again after long-term PTZ injection with GAD65 reduction to baseline level.
期刊介绍：
Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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