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Pancreatic Cancer-Associated Depression (PCAD) is Linked to Adult Neurogenesis Impairment

Postgraduate Thesis uoadl:3446406 7 Read counter

Unit:
Κατεύθυνση Νευροεπιστήμες
Library of the School of Science
Deposit date:
2024-12-11
Year:
2024
Author:
Troumpoukis Dimitrios
Supervisors info:
Yassemi Koutmani, Staff Research Scientist, BRFAA
Alexia Polissidis, Research Scientist, BRFAA
Ioannis Sotiropoulos, Researcher C, NCSR Demokritos
Original Title:
Pancreatic Cancer-Associated Depression (PCAD) is Linked to Adult Neurogenesis Impairment
Languages:
English
Translated title:
Pancreatic Cancer-Associated Depression (PCAD) is Linked to Adult Neurogenesis Impairment
Summary:
Pancreatic Cancer (PC) is a very aggressive type of cancer, associated with a high incidence of major depression (PCAD) manifesting before formal diagnosis. Our study investigates how PC affects the brain and particularly adult neurogenesis (AN), leading to depression. First, we generated a PC mouse model by orthotopically injecting pancreatic cancer cells into NOD-SCID mice pancreas. Behavioral tests on these mice revealed a depressive-like phenotype compared to controls. Immunohistological analysis showed impaired adult neurogenic activity and a diminished Neural Stem Cell (NSC) pool, suggesting an impact of PC on adult neurogenesis. The same phenotype was also evident in a genetic mouse model of PC (Pdx1Cre-AKrasG12D), supporting the impact of PC on AN. Exposure of wild-type NSCs to serum isolated from these mice, resulted in reduced proliferation and survival of NSCs suggesting the involvement of systemic factors on AN impairment. Multiplex analysis of these serum samples demonstrated significantly increased levels of specific pro-inflammatory factors; IL-6, MCP-1 and G-CSF in NOD-SCID mice with PC, and TNFa, IL-1b, IL-1a and G-CSF in Pdx1Cre-AKrasG12D mice. Additionally, serotonin and glutamine pathways were significantly altered in both mouse models. Our findings suggest an AN-linked mechanism for PCAD and identifies specific pro-inflammatory factors as key components in this process.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
Pancreatic Cancer, Depression, PCAD, Adult Neurogenesis, Neural Stem Cells, Serotonin, Inflammation, Neurospheres, Hippocampus.
Index:
No
Number of index pages:
0
Contains images:
No
Number of references:
55
Number of pages:
40
File:
File access is restricted until 2027-12-13.
Persistent URL:
https://pergamos.lib.uoa.gr/uoa/dl/object/3446406

PDF file


MSc thesis DT.pdf
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File access is restricted until 2027-12-13.

 

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