Abstract：
:The Forkhead Box G1 (FOXG1) gene encodes a transcription factor with an essential role in mammalian telencephalon development. FOXG1-related disorders, caused by deletions, intragenic mutations or duplications, are usually associated with severe intellectual disability, autistic features, and, in 87% of subjects, epileptiform manifestations. In a subset of patients with FoxG1 mutations, seizures remain intractable, prompting the need for novel therapeutic options. To address this issue, we took advantage of a haploinsufficient animal model, the FoxG1+/- mouse. In vivo electrophysiological analyses of FoxG1+/- mice detected hippocampal hyperexcitability, which turned into overt seizures upon delivery of the proconvulsant kainic acid, as confirmed by behavioral observations. These alterations were associated with decreased expression of the chloride transporter KCC2. Next, we tested whether a triheptanoin-based anaplerotic diet could have an impact on the pathological phenotype of FoxG1+/- mice. This manipulation abated altered neural activity and normalized enhanced susceptibility to proconvulsant-induced seizures, in addition to rescuing altered expression of KCC2 and increasing the levels of the GABA transporter vGAT. In conclusion, our data show that FoxG1 haploinsufficiency causes dysfunction of hippocampal circuits and increases the susceptibility to a proconvulsant insult, and that these alterations are rescued by triheptanoin dietary treatment.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Testa G,Mainardi M,Olimpico F,Pancrazi L,Cattaneo A,Caleo M,Costa Mdoi
10.1016/j.neuropharm.2019.01.005subject
Has Abstractpub_date
2019-04-01 00:00:00pages
305-310eissn
0028-3908issn
1873-7064pii
S0028-3908(19)30005-Xjournal_volume
148pub_type
杂志文章abstract：:The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the synthesis and release of dopamine (DA) was investigated in the retina of the rabbit in vitro. The results indicated that MPTP did not affect the synthesis of DA, but increased its release. Blockade of the activity of monoamine oxidase (MAO) with...
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
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abstract：:Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary me...
journal_title：Neuropharmacology
pub_type： 杂志文章
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abstract：:The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson...
journal_title：Neuropharmacology
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更新日期：2017-05-01 00:00:00
