d-Serine Intervention In The Medial Entorhinal Area Alters TLE-Related Pathology In CA1 Hippocampus Via The Temporoammonic Pathway.
d-Serine Intervention In The Medial Entorhinal Area Alters TLE-Related Pathology In CA1 Hippocampus Via The Temporoammonic Pathway.
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DOI：
10.1016/j.neuroscience.2020.10.025
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发表时间：
2021-01-15
期刊：
影响因子：
3.3
通讯作者：
Kumar SS
中科院分区：
文献类型：
--
作者：
Beesley S;Sullenberger T;Ailani R;D'Orio C;Crockett MS;Kumar SS
Entrainment of the hippocampus by the medial entorhinal area (MEA) in Temporal Lobe Epilepsy (TLE), the most common type of drug-resistant epilepsy in adults, is believed to be mediated primarily through the perforant pathway (PP), which connects stellate cells in layer (L) II of the MEA with granule cells of the dentate gyrus (DG) to drive the hippocampal tri-synaptic circuit. Using immunohistochemistry, high-resolution confocal microscopy and the rat pilocarpine model of TLE, we show here that the lesser known temporoammonic pathway (TAP) plays a significant role in transferring MEA pathology to the CA1 region of the hippocampus independently of the PP. The pathology observed was region-specific and restricted primarily to the CA1c subfield of the hippocampus. As shown previously, daily intracranial infusion of D-serine (100 μm), an antagonist of GluN3-containing triheteromeric N-Methyl D-aspartate receptors (t-NMDARs), into the MEA prevented loss of LIII neurons and epileptogenesis. This intervention in the MEA led to the rescue of hippocampal CA1 neurons that would have otherwise perished in the epileptic animals, and down regulation of the expression of astrocytes and microglia thereby mitigating the effects of neuroinflammation. Interestingly, these changes were not observed to a similar extent in other regions of vulnerability like the hilus, DG or CA3, suggesting that the pathology manifest in CA1 is driven predominantly through the TAP. This work highlights TAP’s role in the entrainment of the hippocampus and identifies specific areas for therapeutic intervention in dealing with TLE.
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影响因子：
5.3
作者：
Djukic, Biljana;Casper, Kristen B.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
影响因子：
5.3
作者：
Fellin, Tommaso;Gomez-Gonzalo, Marta;Haydon, Philip G.
通讯作者：
Haydon, Philip G.
DOI：
10.1126/science.aaa5694
发表时间：
2016-01-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Siegelbaum SA
影响因子：
4.7
作者：
Drexel M;Preidt AP;Sperk G
通讯作者：
Sperk G
影响因子：
2.9
作者：
Fujikawa, DG
通讯作者：
Fujikawa, DG