Analysis of proliferating neuronal progenitors and immature neurons in the human hippocampus surgically removed from control and epileptic patients

Tatsunori Seki,Hajime Miyata,Michiyo Maehara,Tomokatsu Hori,Takashi Namba

doi:10.1038/s41598-019-54684-z

Abstract

Adult neurogenesis in the mammalian hippocampus is a well-known phenomenon. However, it remains controversial as to what extent adult neurogenesis actually occurs in the adult human hippocampus, and how brain diseases, such as epilepsy, affect human adult neurogenesis. To address these questions, we analyzed immature neuronal marker-expressing (PSA-NCAM+) cells and proliferating neuronal progenitor (Ki67+/HuB+/DCX+) cells in the surgically removed hippocampus of epileptic patients. In control patients, a substantial number of PSA-NCAM+ cells were distributed densely below the granule cell layer. In epileptic patients with granule cell dispersion, the number of PSA-NCAM+ cells was reduced, and aberrant PSA-NCAM+ cells were found. However, the numbers of Ki67+/HuB+/DCX+ cells were very low in both control and epileptic patients. The large number of PSA-NCAM+ cells and few DCX+/HuB+/Ki-67+ cells observed in the controls suggest that immature-type neurons are not recently generated neurons, and that the level of hippocampal neuronal production in adult humans is low. These results also suggest that PSA-NCAM is a useful marker for analyzing the pathology of epilepsy, but different interpretations of the immunohistochemical results between humans and rodents are required.

Highlights

Adult neurogenesis in the mammalian hippocampus is a well-known phenomenon
Our present study demonstrates that a substantial number of PSA-NCAM-positive (PSA-NCAM+) cells exist in the human subgranular zone (SGZ) and hilus, and severe epilepsy causes structural changes in PSA-NCAM+ cells, but the number of DCX+/HuB+/Ki67+ proliferating intermediate progenitor cells is very low, suggesting that the majority of immature neuronal marker-positive neurons are not recently generated neurons, but show pathological alterations similar to those seen in newly generated neurons of rodents
Nissl staining showed that granule cells were tightly packed in the granule cell layer (GCL), and large neurons were distributed in the area enclosed by the C-shaped GCL, which consists of the hilus, CA4, and a part of the CA3 pyramidal cell layer (Fig. 1A1–C1, and Supplemental Fig. 1)

Summary

Introduction

It remains controversial as to what extent adult neurogenesis occurs in the adult human hippocampus, and how brain diseases, such as epilepsy, affect human adult neurogenesis To address these questions, we analyzed immature neuronal marker-expressing (PSA-NCAM+) cells and proliferating neuronal progenitor (Ki67+/HuB+/DCX+) cells in the surgically removed hippocampus of epileptic patients. The large number of PSA-NCAM+ cells and few DCX+/HuB+/Ki-67+ cells observed in the controls suggest that immature-type neurons are not recently generated neurons, and that the level of hippocampal neuronal production in adult humans is low. These results suggest that PSA-NCAM is a useful marker for analyzing the pathology of epilepsy, but different interpretations of the immunohistochemical results between humans and rodents are required. It has been reported that seizures enhance the level of neurogenesis in some cases, in young patients[40], but not in other cases[16,41,42]

Methods

Results

Conclusion