PMID- 37801071
OWN - NLM
STAT- MEDLINE
DCOM- 20240415
LR  - 20240422
IS  - 1872-8081 (Electronic)
IS  - 0951-6433 (Linking)
VI  - 50
IP  - 2
DP  - 2024 Mar-Apr
TI  - Neuroprotective effects of vitamin D in an Alzheimer's disease rat model: 
      Improvement of mitochondrial dysfunction via calcium/calmodulin-dependent protein 
      kinase kinase 2 activation of Sirtuin1 phosphorylation.
PG  - 371-391
LID - 10.1002/biof.2013 [doi]
AB  - Mitochondrial dysfunction is an early event in Alzheimer's disease (AD) 
      pathogenesis. To assess the impact of vitamin D3 (Vit.D) on neurogenesis, we 
      investigated its role in mitigating cognitive impairment and mitochondrial 
      dysfunction through calcium/calmodulin-dependent protein kinase kinase 2 
      (CAMKK2)-mediated phosphorylation of Sirtuin1 (SIRT1) in an 
      aluminum-chloride-D-galactose (AlCl3-D-gal)-induced AD rat model. Rats were 
      distributed into four groups: control, AlCl(3) + D-gal (10 + 60 mg/kg, ip), Vit.D 
      (500 IU/kg, po), and AlCl(3) + D-gal+Vit.D. Novel object recognition (NOR), 
      Morris Water Maze, and passive avoidance (PA) tests were used to measure memory 
      abilities. The hippocampal tissue was used to assess vitamin D3 receptor (VDR) 
      and peroxisome-proliferator-activated-receptor-gamma-coactivator-1alpha (PGC-1alpha) 
      expression by quantitative real-time polymerase chain reaction (qRT-PCR), CAMKK2, 
      p-SIRT1, phosphorylated-AMP-activated protein kinase (p-AMPK), 
      dynamin-related-protein-1 (Drp1), and mitofusin-1 (Mnf1) proteins by western blot 
      and Ca(2+) levels, endothelial nitic oxide synthase (eNOS), superoxide dismutase 
      (SOD), amyloid beta (Abeta), and phospho tau (p-Tau) via enzyme-linked immunosorbent 
      assay(ELISA) in addition to histological and ultrastructural examination of rat's 
      brain tissue. Vit.D-attenuated hippocampal injury reversed the cognitive decline 
      and Abeta aggregation, and elevated p-Tau levels in the AlCl(3) + D-gal-induced AD 
      rat model. In AlCl(3) + D-gal-exposed rats, Vit.D induced VDR expression, 
      normalized Ca(2+) levels, elevated CAMKK2, p-AMPK, p-SIRT1, and PGC-1alpha 
      expression. Vit.D reduced Drp1, induced Mnf1, increased mitochondrial membrane 
      potential, preserved mitochondrial structure, restored normal mitochondrial 
      function, and retained normal eNOS level and SOD activity in AlCl(3) + D-gal 
      rats. In conclusion, our findings proved that Vit.D may ameliorate cognitive 
      deficits in AlCl3 + D-gal-induced AD by restoring normal mitochondrial function 
      and reducing inflammatory and oxidative stress via CAMKK2-AMPK/SIRT1 pathway 
      upregulation.
CI  - (c) 2023 International Union of Biochemistry and Molecular Biology.
FAU - Mohanad, Marwa
AU  - Mohanad M
AUID- ORCID: 0000-0002-3827-9647
AD  - Department of Biochemistry, College of Pharmaceutical Sciences and Drug 
      Manufacturing, Misr University for Science and Technology (MUST), Giza, Egypt.
FAU - Mohamed, Shimaa K
AU  - Mohamed SK
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Cairo, Egypt.
FAU - Aboulhoda, Basma E
AU  - Aboulhoda BE
AD  - Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, 
      Cairo, Egypt.
FAU - Ahmed, Maha A E
AU  - Ahmed MAE
AD  - Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and 
      Drug Manufacturing, Misr University for Science and Technology (MUST), Giza, 
      Egypt.
LA  - eng
PT  - Journal Article
DEP - 20231006
PL  - Netherlands
TA  - Biofactors
JT  - BioFactors (Oxford, England)
JID - 8807441
RN  - 3CYT62D3GA (Aluminum Chloride)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Amyloid beta-Peptides)
RN  - SY7Q814VUP (Calcium)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - 0 (Neuroprotective Agents)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - 1406-16-2 (Vitamin D)
RN  - 0 (Vitamins)
SB  - IM
MH  - Animals
MH  - Rats
MH  - Aluminum Chloride
MH  - *Alzheimer Disease/drug therapy/genetics
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/metabolism
MH  - *Mitochondrial Diseases/drug therapy
MH  - *Neuroprotective Agents/pharmacology/therapeutic use
MH  - Phosphorylation
MH  - *Sirtuin 1/drug effects/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - *Vitamin D/pharmacology/therapeutic use
MH  - Vitamins
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - CAMKK2/AMPK/SIRT1/PGC-1alpha signaling pathway
OT  - memory
OT  - mitochondrial dynamics
OT  - vitamin D
EDAT- 2023/10/06 12:44
MHDA- 2024/04/15 06:43
CRDT- 2023/10/06 10:43
PHST- 2023/05/12 00:00 [received]
PHST- 2023/09/17 00:00 [accepted]
PHST- 2024/04/15 06:43 [medline]
PHST- 2023/10/06 12:44 [pubmed]
PHST- 2023/10/06 10:43 [entrez]
AID - 10.1002/biof.2013 [doi]
PST - ppublish
SO  - Biofactors. 2024 Mar-Apr;50(2):371-391. doi: 10.1002/biof.2013. Epub 2023 Oct 6.