期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 72, 期 7, 页码 1500-1515出版社
SPRINGERNATURE
DOI: 10.1007/s12031-022-02041-7
关键词
Epilepsy; Chloride homeostasis; K+-Cl- co-transporter 2 (KCC2); Neuronal excitability
资金
- European Regional Development Fund (ERDF) [CENTRO-01-0145-FEDER-030659]
- FCT - Fundacao para a Ciencia e a Tecnologia [UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020]
- Liga Portuguesa Contra a Epilepsia (LPCE)
- FCT [2020.00420.CEECIND]
Epilepsy is a neurological disease characterized by abnormal brain activity leading to seizures and various symptoms. Apart from seizures, patients with epilepsy may also experience cognitive deficits, emotional issues, and psychiatric disorders. Current treatments include medication and surgery, but a portion of patients develop drug resistance. Therefore, further research is needed to understand the causes of epilepsy and develop innovative treatment strategies.
Epilepsy is a neurological disease characterized by abnormal or synchronous brain activity causing seizures, which may produce convulsions, minor physical signs, or a combination of symptoms. These disorders affect approximately 65 million people worldwide, from all ages and genders. Seizures apart, epileptic patients present a high risk to develop neuropsychological comorbidities such as cognitive deficits, emotional disturbance, and psychiatric disorders, which severely impair quality of life. Currently, the treatment for epilepsy includes the administration of drugs or surgery, but about 30% of the patients treated with antiepileptic drugs develop time-dependent pharmacoresistence. Therefore, further investigation about epilepsy and its causes is needed to find new pharmacological targets and innovative therapeutic strategies. Pharmacoresistance is associated to changes in neuronal plasticity and alterations of GABA(A) receptor-mediated neurotransmission. The downregulation of GABA inhibitory activity may arise from a positive shift in GABA(A) receptor reversal potential, due to an alteration in chloride homeostasis. In this paper, we review the contribution of K+-Cl--cotransporter (KCC2) to the alterations in the Cl- gradient observed in epileptic condition, and how these alterations are coupled to the increase in the excitability.
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