التفاصيل البيبلوغرافية
| العنوان: |
Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism |
| المؤلفون: |
Antonella De Jaco, Dalila Mango, Federica De Angelis, Flores Favaloro, Diego Andolina, Robert Nisticò, Elena Fiori, Marco Colamartino, Tiziana Pascucci |
| المصدر: |
International Journal of Molecular Sciences; Volume 18; Issue 5; Pages: 941 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2017 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
neurotransmission, excitation and inhibition balance, cognitive delay, prefrontal cortex, neuroligins |
| جغرافية الموضوع: |
agris |
| الوصف: |
Phenylketonuria (PKU) is the most common genetic metabolic disease with a well-documented association with autism spectrum disorders. It is characterized by the deficiency of the phenylalanine hydroxylase activity, causing plasmatic hyperphenylalaninemia and variable neurological and cognitive impairments. Among the potential pathophysiological mechanisms implicated in autism spectrum disorders is the excitation/inhibition (E/I) imbalance which might result from alterations in excitatory/inhibitory synapse development, synaptic transmission and plasticity, downstream signalling pathways, and intrinsic neuronal excitability. Here, we investigated functional and molecular alterations in the prefrontal cortex (pFC) of BTBR-Pahenu2 (ENU2) mice, the animal model of PKU. Our data show higher frequency of inhibitory transmissions and significant reduced frequency of excitatory transmissions in the PKU-affected mice in comparison to wild type. Moreover, in the pFC of ENU2 mice, we reported higher levels of the post-synaptic cell-adhesion proteins neuroligin1 and 2. Altogether, our data point toward an imbalance in the E/I neurotransmission favouring inhibition in the pFC of ENU2 mice, along with alterations of the molecular components involved in the organization of cortical synapse. In addition to being the first evidence of E/I imbalance within cortical areas of a mouse model of PKU, our study provides further evidence of E/I imbalance in animal models of pathology associated with autism spectrum disorders. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms18050941 |
| DOI: |
10.3390/ijms18050941 |
| الاتاحة: |
https://doi.org/10.3390/ijms18050941 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.2977763E |
| قاعدة البيانات: |
BASE |