Human adult neurogenesis across the ages: An immunohistochemical study

Abstract

Aims Neurogenesis in the postnatal human brain occurs in two neurogenic niches; the subventricular zone (SVZ) in the wall of the lateral ventricles and the subgranular zone of the hippocampus (SGZ). The extent to which this physiological process continues into adulthood is an area of ongoing research. This study aimed to characterise markers of cell proliferation and assess the efficacy of antibodies used to identify neurogenesis in both neurogenic niches of the human brain. Methods Cell proliferation and neurogenesis were simultaneously examined in the SVZ and SGZ of 23 individuals aged 0.2–59 years using immunohistochemistry and immunofluorescence in combination with unbiased stereology. Results There was a marked decline in proliferating cells in both neurogenic niches in early infancy with levels reaching those seen in the adjacent parenchyma by four and one year of age, in the SVZ and SGZ, respectively. Furthermore, the phenotype of these proliferating cells in both niches changed with age. In infants, proliferating cells co-expressed neural progenitor (epidermal growth factor receptor), immature neuronal (doublecortin and beta III tubulin) and oligodendrocytic (Olig2) markers. However, after three years of age, microglia were the only proliferating cells found in either niche or in the adjacent parenchyma. Conclusions This study demonstrates a marked decline in neurogenesis in both neurogenic niches in early childhood, and that the sparse proliferating cells in the adult brain are largely microglia.

Response to: Comment on ‘Human adult neurogenesis across the ages: An immunohistochemical study’

“…Overall, the sparse neuroblasts in the neurogenic niches of the adult human brain reported in numerous studies , including our recent report is in stark contrast to that seen in infants. In our opinion, this is indicative of a vestigial process in the neurologically normal brain after infancy.…”

“…Fig. 1G ) although these were not specifically described in our original article. However, in the absence of colocalization data, it is not possible to determine the lineage of their cells.…”

Alzheimer Disease

“…There is a decline with aging, 48 and the degree of ongoing neurogenesis in the adult human brain is still debated. (A recent estimate indicates that the rates of adult neurogenesis in the subventricular and subgranular zones approach that of the surrounding parenchyma and reflect microglia rather than neurons 49 ).…”

Decline in Proliferation and Immature Neuron Markers in the Human Subependymal Zone during Aging: Relationship to EGF- and FGF-Related Transcripts

“…While some groups find little evidence for a rostral migratory stream or significant cellular proliferation in the human SEZ after the early postnatal period (Arellano and Rakic, 2011; Sanai et al, 2011; Dennis et al, 2016), others demonstrate the existence of a rostral migratory stream in humans as well as the presence of proliferating cells and immature neurons in the adult SEZ (Curtis et al, 2007; Kam et al, 2009; Tepavcevic et al, 2011; Wang et al, 2011; Maheu et al, 2015). Furthermore, SEZ precursor cells derived from elderly humans have the capacity to generate neurons and glia in vitro (Kukekov et al, 1999; Leonard et al, 2009; van Strien et al, 2014), supporting the continued existence of neural precursor cells even during aging.…”