Investigation of synapses in the cortical white matter in human temporal lobe epilepsy

Cortical Layer Markers Expression and Increased Synaptic Density in Interstitial Neurons of the White Matter from Drug-Resistant Epilepsy Patients

“…Therefore, the increased glutamatergic and GABAergic synaptic density of interstitial neurons in the white matter could be integrated into the epileptic neuronal networks and contribute to seizure genesis in drug-resistant epilepsy. Consistent with our findings, a recent study showed that the synaptic density in the neocortical white matter of TLE patients was significantly higher than that of controls, and the synaptic density in the white matter was significantly correlated with the postoperative prognosis of drug-resistant epilepsy patients with TLE [ 14 ]. Together, these results suggested that interstitial neurons in the white matter of the adult human brain could potentially participate in the epileptic network and contribute to seizure genesis in drug-resistant epilepsy.…”

“…Interstitial neurons were considered to be remnant of subplate neurons that survived after apoptosis in the white matter during postnatal brain development [ 29 ]. Embryonic birth-dating lineage tracing in monkeys and carnivores suggested that interstitial neurons shared the same developmental origin with subplate neurons and deep-layer cortical neurons [ 11 , 14 , 15 ]. The expression of cortical layer markers CUX2, TLE4, and FOXP1 were identified in the embryonic human subplate [ 30 ], these neurons were considered as immature migratory neurons that co-expressed with DCX [ 31 ].…”

“…Morphological analysis by Golgi staining revealed the presence of spines in the dendritic trees of interstitial neurons that could extend to the deep layer of the cortex [ 2 ]. Both symmetric and asymmetric synaptic structures are identified in the perikarya and dendrites of interstitial neurons by electron microscopy or immunohistochemistry, suggesting the presence of both glutamatergic and GABAergic synapses in interstitial neurons in the white matter [ 2 , 7 , 14 ]. Malformations of cortical development are common causes of drug-resistant epilepsy that are usually accompanied by disordered cortical stratification and indistinct gray and white matter boundaries [ 15 ].…”

Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease

“…Synaptic structures in WM have previously been observed and may be related to modulation of oligodendrocytes and astrocytes, though the significance of their downregulation in AD remains to be characterized 56,57 . A similar involvement of synaptic input has also been observed in the cortical WM in human temporal lobe epilepsy 58 , suggesting the involvement of synaptic dysregulation in WM. In sum, this highlights key differences in the molecular changes taking place between frontal- and occipital-WM in AD.…”