PMID- 36226387
OWN - NLM
STAT- MEDLINE
DCOM- 20221205
LR  - 20221227
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 56
IP  - 11
DP  - 2022 Dec
TI  - Impaired spatial navigation and age-dependent hippocampal synaptic dysfunction 
      are associated with chronic inflammatory response in db/db mice.
PG  - 6003-6021
LID - 10.1111/ejn.15835 [doi]
AB  - Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer's 
      disease (AD), which has been proposed to be driven by an abnormal 
      neuroinflammatory response affecting cognitive function. However, the impact of 
      T2DM on hippocampal function and synaptic integrity during aging has not been 
      investigated. Here, we investigated the effects of aging in T2DM on AD-like 
      pathology using the leptin receptor-deficient db/db mouse model of T2DM. Our 
      results indicate that adult T2DM mice exhibited impaired spatial acquisition in 
      the Morris water maze (MWM). Morphological analysis showed an age-dependent 
      neuronal loss in the dentate gyrus. We found that astrocyte density was 
      significantly decreased in all regions of the hippocampus in T2DM mice. 
      Our analysis showed that microglial activation was increased in the CA3 and the 
      dentate gyrus of the hippocampus in an age-dependent manner in T2DM mice. 
      However, the expression of presynaptic marker protein (synaptophysin) and the 
      postsynaptic marker protein [postsynaptic density protein 95 (PSD95)] was 
      unchanged in the hippocampus of adult T2DM mice. Interestingly, synaptophysin and 
      PSD95 expression significantly decreased in the hippocampus of aged T2DM mice, 
      suggesting an impaired hippocampal synaptic integrity. Cytokine profiling 
      analysis displayed a robust pro-inflammatory cytokine profile in the hippocampus 
      of aged T2DM mice compared with the younger cohort, outlining the role of aging 
      in exacerbating the neuroinflammatory profile in the diabetic state. Our results 
      suggest that T2DM impairs cognitive function by promoting neuronal loss in the 
      dentate gyrus and triggering an age-dependent deterioration in hippocampal 
      synaptic integrity, associated with an aberrant neuroinflammatory response.
CI  - (c) 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Al-Onaizi, Mohammed
AU  - Al-Onaizi M
AUID- ORCID: 0000-0003-3934-4233
AD  - Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, 
      Kuwait.
FAU - Al-Sarraf, Ahmad
AU  - Al-Sarraf A
AUID- ORCID: 0000-0001-9289-3763
AD  - Undergraduate Medical Degree Program, Faculty of Medicine, Kuwait University, 
      Kuwait City, Kuwait.
FAU - Braysh, Kawthar
AU  - Braysh K
AD  - Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, 
      Kuwait.
FAU - Kazem, Fatema
AU  - Kazem F
AD  - Undergraduate Medical Degree Program, Faculty of Medicine, Kuwait University, 
      Kuwait City, Kuwait.
FAU - Al-Hussaini, Heba
AU  - Al-Hussaini H
AD  - Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, 
      Kuwait.
FAU - Rao, Muddanna
AU  - Rao M
AD  - Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, 
      Kuwait.
FAU - Kilarkaje, Narayana
AU  - Kilarkaje N
AD  - Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, 
      Kuwait.
FAU - ElAli, Ayman
AU  - ElAli A
AD  - Neuroscience Axis, Research Center of CHU de Quebec, Universite Laval, Quebec 
      City, Quebec, Canada.
AD  - Department of Psychiatry and Neuroscience, Faculty of Medicine, Universite Laval, 
      Quebec City, Quebec, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221028
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Synaptophysin)
RN  - 0 (Cytokines)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Synaptophysin/metabolism
MH  - *Spatial Navigation
MH  - *Diabetes Mellitus, Type 2
MH  - Hippocampus/metabolism
MH  - *Alzheimer Disease/metabolism
MH  - Inflammation/metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - cytokines
OT  - diabetes mellitus
OT  - hippocampus
OT  - memory
OT  - neuroinflammation
EDAT- 2022/10/14 06:00
MHDA- 2022/12/06 06:00
CRDT- 2022/10/13 03:24
PHST- 2022/08/18 00:00 [revised]
PHST- 2021/04/07 00:00 [received]
PHST- 2022/09/23 00:00 [accepted]
PHST- 2022/10/14 06:00 [pubmed]
PHST- 2022/12/06 06:00 [medline]
PHST- 2022/10/13 03:24 [entrez]
AID - 10.1111/ejn.15835 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2022 Dec;56(11):6003-6021. doi: 10.1111/ejn.15835. Epub 2022 Oct 
      28.