D-serine mitigates cell loss associated with temporal lobe epilepsy.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 10 2020
02 10 2020
Historique:
received:
26
12
2019
accepted:
09
09
2020
entrez:
3
10
2020
pubmed:
4
10
2020
medline:
21
10
2020
Statut:
epublish
Résumé
Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults, with an unknown etiology. A hallmark of TLE is the characteristic loss of layer 3 neurons in the medial entorhinal area (MEA) that underlies seizure development. One approach to intervention is preventing loss of these neurons through better understanding of underlying pathophysiological mechanisms. Here, we show that both neurons and glia together give rise to the pathology that is mitigated by the amino acid D-serine whose levels are potentially diminished under epileptic conditions. Focal administration of D-serine to the MEA attenuates neuronal loss in this region thereby preventing epileptogenesis in an animal model of TLE. Additionally, treatment with D-serine reduces astrocyte counts in the MEA, alters their reactive status, and attenuates proliferation and/or infiltration of microglia to the region thereby curtailing the deleterious consequences of neuroinflammation. Given the paucity of compounds that reduce hyperexcitability and neuron loss, have anti-inflammatory properties, and are well tolerated by the brain, D-serine, an endogenous amino acid, offers new hope as a therapeutic agent for refractory TLE.
Identifiants
pubmed: 33009404
doi: 10.1038/s41467-020-18757-2
pii: 10.1038/s41467-020-18757-2
pmc: PMC7532172
doi:
Substances chimiques
Serine
452VLY9402
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4966Subventions
Organisme : NINDS NIH HHS
ID : R01 NS097802
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA044442
Pays : United States
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