Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression

被引:0
作者
Xiong, Zhonghua [1 ,2 ]
Deng, Jiahui [1 ]
Xie, Pandeng [1 ,3 ]
Tang, Chongyang [1 ,3 ]
Wang, Jing [1 ,2 ]
Deng, Qinqin [1 ,2 ]
Yang, Yujiao [1 ,2 ]
Zhang, Jing [1 ,2 ]
Guo, Mengyi [1 ,2 ]
Wang, Xiongfei [1 ,3 ]
Guan, Yuguang [1 ,3 ]
Luan, Guoming [1 ,3 ]
Zhou, Jian [1 ,3 ]
Li, Tianfu [1 ,2 ]
机构
[1] Capital Med Univ, Beijing Inst Brain Disorders, Sanbo Brain Hosp, Dept Brian Inst, Beijing, Peoples R China
[2] Capital Med Univ, Beijing Inst Brain Disorders, Sanbo Brain Hosp, Dept Neurol, Beijing, Peoples R China
[3] Capital Med Univ, Beijing Inst Brain Disorders, Sanbo Brain Hosp, Dept Neurosurg, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
Adenosine; Deep brain stimulation; Epilepsy; CD39; CD73; ENT1; ELECTRICAL-STIMULATION; ANTERIOR NUCLEUS; UP-REGULATION; KINASE; EPILEPTOGENESIS; THALAMUS; NUCLEOTIDASES; HIPPOCAMPAL; TRANSPORTER; CEREBELLAR;
D O I
10.1007/s12035-024-04374-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naive rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.
引用
收藏
页码:1800 / 1812
页数:13
相关论文
共 60 条
[1]   Long-term follow-up of patients with thalamic deep brain stimulation for epilepsy [J].
Andrade, D. M. ;
Zumsteg, D. ;
Hamani, C. ;
Hodaie, M. ;
Sarkissian, S. ;
Lozano, A. M. ;
Wennberg, R. A. .
NEUROLOGY, 2006, 66 (10) :1571-1573
[2]   Increased ATP release and CD73-mediated adenosine A2A receptor activation mediate convulsion-associated neuronal damage and hippocampal dysfunction [J].
Augusto, Elisabete ;
Goncalves, Francisco Q. ;
Real, Joana E. ;
Silva, Henrique B. ;
Pochmann, Daniela ;
Silva, Tiago S. ;
Matos, Marco ;
Goncalves, Nelio ;
Tome, Angelo R. ;
Chen, Jiang-Fan ;
Canas, Paula M. ;
Cunha, Rodrigo A. .
NEUROBIOLOGY OF DISEASE, 2021, 157
[3]   Adenosine A2A receptor and ecto-5'-nucleotidase/CD73 are upregulated in hippocampal astrocytes of human patients with mesial temporal lobe epilepsy (MTLE) [J].
Barros-Barbosa, Aurora R. ;
Ferreirinha, Fatima ;
Oliveira, Angela ;
Mendes, Marina ;
Graca Lobo, M. ;
Santos, Agostinho ;
Rangel, Rui ;
Pelletier, Julie ;
Sevigny, Jean ;
Miguel Cordeiro, J. ;
Correia-de-Sa, Paulo .
PURINERGIC SIGNALLING, 2016, 12 (04) :719-734
[4]   Epigenetics and epilepsy prevention: The therapeutic potential of adenosine and metabolic therapies [J].
Boison, Detlev ;
Rho, Jong M. .
NEUROPHARMACOLOGY, 2020, 167
[5]   Role of adenosine in status epilepticus: A potential new target? [J].
Boison, Detlev .
EPILEPSIA, 2013, 54 :20-22
[6]   Adenosine Kinase: Exploitation for Therapeutic Gain [J].
Boison, Detlev .
PHARMACOLOGICAL REVIEWS, 2013, 65 (03) :906-943
[7]   Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy [J].
Brodie, M. J. ;
Perucca, E. ;
Ryvlin, P. ;
Ben-Menachem, E. ;
Meencke, H. -J. .
NEUROLOGY, 2007, 68 (06) :402-408
[8]   Purinergic signalling and disorders of the central nervous system [J].
Burnstock, Geoffrey .
NATURE REVIEWS DRUG DISCOVERY, 2008, 7 (07) :575-590
[9]   Role of DNA Methylation and Adenosine in Ketogenic Diet for Pharmacoresistant Epilepsy: Focus on Epileptogenesis and Associated Comorbidities [J].
Chen, Fan ;
He, Xinghui ;
Luan, Guoming ;
Li, Tianfu .
FRONTIERS IN NEUROLOGY, 2019, 10
[10]   CHRONIC CEREBELLAR STIMULATION IN EPILEPSY [J].
COOPER, IS ;
AMIN, I ;
RIKLAN, M ;
WALTZ, JM ;
POON, TP .
ARCHIVES OF NEUROLOGY, 1976, 33 (08) :559-570