PMID- 33004912
OWN - NLM
STAT- MEDLINE
DCOM- 20210101
LR  - 20240429
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Oct 1
TI  - Deficits in hippocampal neurogenesis in obesity-dependent and -independent type-2 
      diabetes mellitus mouse models.
PG  - 16368
LID - 10.1038/s41598-020-73401-9 [doi]
LID - 16368
AB  - Hippocampal neurogenesis plays an important role in learning and memory function 
      throughout life. Declines in this process have been observed in both aging and 
      Alzheimer's disease (AD). Type 2 Diabetes mellitus (T2DM) is a disorder 
      characterized by insulin resistance and impaired glucose metabolism. T2DM often 
      results in cognitive decline in adults, and significantly increases the risk of 
      AD development. The pathways underlying T2DM-induced cognitive deficits are not 
      known. Some studies suggest that alterations in hippocampal neurogenesis may 
      contribute to cognitive deterioration, however, the fate of neurogenesis in these 
      studies is highly controversial. To address this problem, we utilized two models 
      of T2DM: (1) obesity-independent MKR transgenic mice expressing a mutated form of 
      the human insulin-like growth factor 1 receptor (IGF-1R) in skeletal muscle, and 
      (2) Obesity-dependent db/db mice harboring a mutation in the leptin receptor. Our 
      results show that both models of T2DM display compromised hippocampal 
      neurogenesis. We show that the number of new neurons in the hippocampus of these 
      mice is reduced. Clone formation capacity of neural progenitor cells isolated 
      from the db/db mice is deficient. Expression of insulin receptor and epidermal 
      growth factor receptor was reduced in hippocampal neurospheres isolated from 
      db/db mice. Results from this study warrant further investigation into the 
      mechanisms underlying decreased neurogenesis in T2DM and its link to the 
      cognitive decline observed in this disorder.
FAU - Bonds, Jacqueline A
AU  - Bonds JA
AD  - Department of Anatomy and Cell Biology, University of Illinois at Chicago, 578 
      CME (M/C 512), 808 South Wood Street, Chicago, IL, 60612, USA.
FAU - Shetti, Aashutosh
AU  - Shetti A
AD  - Department of Anatomy and Cell Biology, University of Illinois at Chicago, 578 
      CME (M/C 512), 808 South Wood Street, Chicago, IL, 60612, USA.
FAU - Stephen, Terilyn K L
AU  - Stephen TKL
AD  - Department of Anatomy and Cell Biology, University of Illinois at Chicago, 578 
      CME (M/C 512), 808 South Wood Street, Chicago, IL, 60612, USA.
FAU - Bonini, Marcelo G
AU  - Bonini MG
AD  - Division of Hematology/Oncology, Department of Medicine, Feinberg School of 
      Medicine and The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of 
      Medicine of Northwestern University, Chicago, IL, 60612, USA.
FAU - Minshall, Richard D
AU  - Minshall RD
AUID- ORCID: 0000-0003-3164-475X
AD  - Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, 
      60612, USA.
AD  - Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, 
      60612, USA.
FAU - Lazarov, Orly
AU  - Lazarov O
AUID- ORCID: 0000-0002-5887-948X
AD  - Department of Anatomy and Cell Biology, University of Illinois at Chicago, 578 
      CME (M/C 512), 808 South Wood Street, Chicago, IL, 60612, USA. olazarov@uic.edu.
LA  - eng
GR  - AG033570/AG/NIA NIH HHS/United States
GR  - AG057468/AG/NIA NIH HHS/United States
GR  - AG060238/AG/NIA NIH HHS/United States
GR  - R01 ES028149/ES/NIEHS NIH HHS/United States
GR  - T32AG057468/AG/NIA NIH HHS/United States
GR  - AG061628/AG/NIA NIH HHS/United States
GR  - ES028149/NH/NIH HHS/United States
GR  - R01 AG062251/AG/NIA NIH HHS/United States
GR  - AG033570-S2/AG/NIA NIH HHS/United States
GR  - AG062251/AG/NIA NIH HHS/United States
GR  - R01 AG060238/AG/NIA NIH HHS/United States
GR  - RF1 AG033570/AG/NIA NIH HHS/United States
GR  - R21 AG061628/AG/NIA NIH HHS/United States
GR  - R56 ES028149/ES/NIEHS NIH HHS/United States
GR  - AG033570-S1/AG/NIA NIH HHS/United States
GR  - T32 AG057468/AG/NIA NIH HHS/United States
GR  - R01 AI131267/AI/NIAID NIH HHS/United States
GR  - R01 AG033570/AG/NIA NIH HHS/United States
GR  - AI131267/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201001
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Igf1r protein, mouse)
RN  - 0 (Receptors, Leptin)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/physiology
MH  - Cognitive Dysfunction/genetics/physiopathology
MH  - Diabetes Mellitus, Type 2/genetics/*physiopathology
MH  - Hippocampus/*physiopathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Neural Stem Cells/physiology
MH  - Neurogenesis/*physiology
MH  - Neurons/*physiology
MH  - Obesity/genetics/*physiopathology
MH  - Receptor, IGF Type 1/genetics
MH  - Receptors, Leptin/genetics
PMC - PMC7530538
COIS- The authors declare no competing interests.
EDAT- 2020/10/03 06:00
MHDA- 2021/01/02 06:00
PMCR- 2020/10/01
CRDT- 2020/10/02 05:39
PHST- 2020/05/26 00:00 [received]
PHST- 2020/09/16 00:00 [accepted]
PHST- 2020/10/02 05:39 [entrez]
PHST- 2020/10/03 06:00 [pubmed]
PHST- 2021/01/02 06:00 [medline]
PHST- 2020/10/01 00:00 [pmc-release]
AID - 10.1038/s41598-020-73401-9 [pii]
AID - 73401 [pii]
AID - 10.1038/s41598-020-73401-9 [doi]
PST - epublish
SO  - Sci Rep. 2020 Oct 1;10(1):16368. doi: 10.1038/s41598-020-73401-9.