Adeno-associated viral vector-mediated preprosomatostatin expression suppresses induced seizures in kindled rats

作者：Natarajan Gowri; Leibowitz Jeffrey A; Zhou Junli; Zhao Yang; McElroy Jessica A; King Michael A; Ormerod Brandi K; Carney Paul R

来源：Epilepsy Research, 2017, 130: 81-92.

DOI：10.1016/j.eplepsyres.2017.01.002

• Hippocampus
• Gene therapy
• Neuropeptides
• Somatostatin
• Kindling
• Adeno-associated viral vectors

Somatostatin is expressed widely in the hippocampus and notably in hilar GABAergic neurons that are vulnerable to seizure neuropathology in chronic temporal lobe epilepsy. We previously demonstrated that sustained bilateral preprosomatostatin (preproSST) expression in the hippocampus prevents the development of generalized seizures in the amygdala kindling model of temporal lobe epilepsy. Here we tested whether sustained preproSST expression is anticonvulsant in rats already kindled to high-grade seizures. Rats were kindled until they exhibited 3 consecutive Racine Grade 5 seizures before adeno-associated virus serotype 5 (AAV5) vector driving either eGFP (AAV5-CBa-eGFP) or preproSST and eGFP (AAV5-CBa-preproSST-eGFP) expression was injected bilaterally into the hippocampal dentate gyrus and CAl region. Retested 3 weeks later, rats that received control vector (AAV5-CBa-eGFP) continued to exhibit high-grade seizures whereas 6/13 rats that received preproSST vector (AAV5-CBa-preproSSTeGFP) were seizure-free. Of these rats, 5/6 remained seizure-free after repeated stimulation sessions and when the stimulation current was increased. These results suggest that vector-mediated expression of preproSST may be a viable therapeutic strategy for temporal lobe epilepsy.

• 出版日期2017-2