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Deciphering Age-Related Decline in Neurogenesis. Focusing on Intermediate Progenitors and Their Reaction to Immune Signalling

Fritze, Jonas LU (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Neurogenesis continues throughout life in two key regions, the subventricular zone (SVZ) and dentate gyrus (DG), but declines with age alongside increased chronic inflammation and microglial activation. These neurogenic niches differ in their susceptibility to systemic changes, with the SVZ located near cerebrospinal fluid and the DG influenced by local neural activity. We found that immune changes, including altered expression of microglia-specific Cx3cr1, leukocyte-specific Cxcr5, systemic cytokine IL-6, and local Cxcl12, specifically impact SVZ intermediate progenitors during aging, leading to distinct effects on neurogenesis in the SVZ compared to the DG. In addition, we identified a subset of SVZ neuroblasts that acquire an immune... (More)
Neurogenesis continues throughout life in two key regions, the subventricular zone (SVZ) and dentate gyrus (DG), but declines with age alongside increased chronic inflammation and microglial activation. These neurogenic niches differ in their susceptibility to systemic changes, with the SVZ located near cerebrospinal fluid and the DG influenced by local neural activity. We found that immune changes, including altered expression of microglia-specific Cx3cr1, leukocyte-specific Cxcr5, systemic cytokine IL-6, and local Cxcl12, specifically impact SVZ intermediate progenitors during aging, leading to distinct effects on neurogenesis in the SVZ compared to the DG. In addition, we identified a subset of SVZ neuroblasts that acquire an immune related transcriptional profile during aging, indicating a potential role in how immune changes influence neurogenesis. Our findings highlight inflammation as a central driver of age-related neurogenic decline and emphasize the need for niche- and age-specific
therapeutic strategies that target immune cells or signalling pathways. (Less)
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author
supervisor
opponent
  • Professor Khodosevich, Konstantin, University of Copenhagen
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Neurogenesis, Aging, Subventricular Zone (SVZ), Dentate Gyrus (DG), Inflammation, Intermediate Progenitors (IPs), Microglia, CX3CR1, CXCR5, Neuroblasts
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024:129
pages
74 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
defense date
2024-11-26 13:00:00
ISSN
1652-8220
ISBN
978-91-8021-627-2
language
English
LU publication?
yes
id
4db0892e-fee3-47df-a18e-75e01b69d919
date added to LUP
2024-11-05 15:04:41
date last changed
2024-11-07 10:14:04
@phdthesis{4db0892e-fee3-47df-a18e-75e01b69d919,
  abstract     = {{Neurogenesis continues throughout life in two key regions, the subventricular zone (SVZ) and dentate gyrus (DG), but declines with age alongside increased chronic inflammation and microglial activation. These neurogenic niches differ in their susceptibility to systemic changes, with the SVZ located near cerebrospinal fluid and the DG influenced by local neural activity. We found that immune changes, including altered expression of microglia-specific Cx3cr1, leukocyte-specific Cxcr5, systemic cytokine IL-6, and local Cxcl12, specifically impact SVZ intermediate progenitors during aging, leading to distinct effects on neurogenesis in the SVZ compared to the DG. In addition, we identified a subset of SVZ neuroblasts that acquire an immune related transcriptional profile during aging, indicating a potential role in how immune changes influence neurogenesis. Our findings highlight inflammation as a central driver of age-related neurogenic decline and emphasize the need for niche- and age-specific<br/>therapeutic strategies that target immune cells or signalling pathways.}},
  author       = {{Fritze, Jonas}},
  isbn         = {{978-91-8021-627-2}},
  issn         = {{1652-8220}},
  keywords     = {{Neurogenesis; Aging; Subventricular Zone (SVZ); Dentate Gyrus (DG); Inflammation; Intermediate Progenitors (IPs); Microglia; CX3CR1; CXCR5; Neuroblasts}},
  language     = {{eng}},
  number       = {{2024:129}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Deciphering Age-Related Decline in Neurogenesis. Focusing on Intermediate Progenitors and Their Reaction to Immune Signalling}},
  url          = {{https://lup.lub.lu.se/search/files/199093491/375177_nr2_G5_Jonas_nosign.pdf}},
  year         = {{2024}},
}