Reduced adult neurogenesis is associated with increased macrophages in the subependymal zone in schizophrenia

Weissleder, Christin; North, Hayley; Bitar, Mainá; Fullerton, Janice M.; Sager, Rachel; Barry, Guy; Piper, Michael; Halliday, Glenda M.; Webster, Maree J.; Weickert, Cynthia Shannon

doi:10.1038/s41380-021-01149-3

Cited by 25 publications

(29 citation statements)

References 99 publications

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“…DCX expression). Critically, we also revealed decreased expression of markers for neurogenesis within the SEZ of patients with schizophrenia and bipolar disorder 14 . These data provide novel insights into adult neurogenesis within the SEZ of patients with psychiatric disorders.…”

Section: Discussionmentioning

confidence: 69%

“…Here, we provide a novel resource to the research community, namely a transcriptomic dataset that describes the changes in gene expression occurring in the SEZ over the course of the entire human lifespan. The RNA sequencing data described here form part of a larger dataset we recently published that investigated changes occurring in the SEZ in patients with schizophrenia 14 . In this study, we provide evidence to support a decrease in the expression of markers for neurogenesis across the course of aging (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, this latter study did reveal the presence of immature neurons within the SEZ of adult humans 8 . Indeed, there is extensive evidence for the existence of ongoing neurogenesis within the postnatal human SEZ 9 – 14 . The question then arises as to the role of SEZ-derived neurogenesis in the mature brain.…”

Section: Introductionmentioning

confidence: 99%

“…Migrating neuroblasts have been found both within the rostral migratory stream 9 and throughout the frontal lobe 16 , 17 , in the first years of life. Although levels of neurogenesis and neurogenic markers drop dramatically within the human SEZ during early childhood 11 , 13 , 14 , 17 , numerous studies have reported ongoing neurogenesis within this neurogenic niche throughout adulthood and advanced age 8 , 12 , 18 , with immature neurons appearing to target the striatum rather than the olfactory bulb 18 .…”

Section: Introductionmentioning

confidence: 99%

“…One question arising from the results found in the developing and aging mouse brain is: How reflective are these changes that occur over 18 months to the cellular and molecular changes that occur over decades within the human SEZ? We have previously used post-mortem human samples to demonstrate that neurogenesis continues throughout the lifespan within the human SEZ 11 – 14 , and that neurogenesis declines during postnatal development 14 , accompanied by decreased mRNA expression of trophic factors and cognate receptors including TRKB and IGF1 13 , 32 . During aging, we see a further reduction in IGF1 as well as increased expression of truncated TRKB and of the microglial marker IBA1 12 , 13 , 32 .…”

Section: Introductionmentioning

confidence: 99%

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Identifying gene expression profiles associated with neurogenesis and inflammation in the human subependymal zone from development through aging

Bitar

Weissleder

North

et al. 2022

Sci Rep

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The generation of new neurons within the mammalian forebrain continues throughout life within two main neurogenic niches, the subgranular zone (SGZ) of the hippocampal dentate gyrus, and the subependymal zone (SEZ) lining the lateral ventricles. Though the SEZ is the largest neurogenic niche in the adult human forebrain, our understanding of the mechanisms regulating neurogenesis from development through aging within this region remains limited. This is especially pertinent given that neurogenesis declines dramatically over the postnatal lifespan. Here, we performed transcriptomic profiling on the SEZ from human post-mortem tissue from eight different life-stages ranging from neonates (average age ~ 2 months old) to aged adults (average age ~ 86 years old). We identified transcripts with concomitant profiles across these decades of life and focused on three of the most distinct profiles, namely (1) genes whose expression declined sharply after birth, (2) genes whose expression increased steadily with age, and (3) genes whose expression increased sharply in old age in the SEZ. Critically, these profiles identified neuroinflammation as becoming more prevalent with advancing age within the SEZ and occurring with time courses, one gradual (starting in mid-life) and one sharper (starting in old age).

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%