PMID- 25510319
OWN - NLM
STAT- MEDLINE
DCOM- 20151124
LR  - 20220309
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 36
IP  - 3
DP  - 2015 Mar
TI  - Central activation of PPAR-gamma ameliorates diabetes induced cognitive 
      dysfunction and improves BDNF expression.
PG  - 1451-61
LID - S0197-4580(14)00634-4 [pii]
LID - 10.1016/j.neurobiolaging.2014.09.028 [doi]
AB  - Diabetes and Alzheimer's disease share pathologic links toward cognitive 
      deficits. Pharmacologic agonist of the nuclear receptor, peroxisomal 
      proliferator-activating receptor gamma (PPARgamma), that is, rosiglitazone (rosi), 
      are insulin sensitizing agents that improve memory in Alzheimer's disease. 
      However, direct molecular signaling targets that improve memory by PPARgamma in the 
      hippocampus have not been investigated. We compared outcomes from oral versus 
      intracerebroventricular (ICV) administration of rosi on memory and changes in 
      synaptic plasticity in type 2 diabetic (db/db) mice. Db/db mice treated with rosi 
      (ICV) showed significant improvement in memory, long-term potentiation, and 
      post-tetanic potentiation but did not improve peripheral insulin sensitivity. 
      Gene and protein analysis revealed increased brain-derived neurotrophic factor 
      (BDNF) in db/db mice treated with rosi (ICV). Transcriptional activation of exon 
      IX as determined by luciferase assays confirmed PPARgamma regulation of BDNF promoter 
      activity. Transient transfection of constitutively active PPARgamma plasmid in 
      hippocampal neuronal cells induced increased BDNF, AMPA, and NMDA receptors 
      expression and spine formation. Findings from the present study implicate a novel 
      PPARgamma-BDNF molecular signaling mechanism as a potential therapeutic target for 
      cognitive impairment.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Kariharan, Thiruchelvam
AU  - Kariharan T
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Nanayakkara, Gayani
AU  - Nanayakkara G
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Parameshwaran, Kodeeswaran
AU  - Parameshwaran K
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Bagasrawala, Inseyah
AU  - Bagasrawala I
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Ahuja, Manuj
AU  - Ahuja M
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Abdel-Rahman, Engy
AU  - Abdel-Rahman E
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Amin, Arin T
AU  - Amin AT
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Dhanasekaran, Murali
AU  - Dhanasekaran M
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Suppiramaniam, Vishnu
AU  - Suppiramaniam V
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA.
FAU - Amin, Rajesh H
AU  - Amin RH
AD  - Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn 
      University, Auburn, AL, USA. Electronic address: rha0003@auburn.edu.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20141002
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Cognition Disorders/*etiology/genetics/psychology/*therapy
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Disease Models, Animal
MH  - Gene Expression/*drug effects
MH  - Hippocampus/metabolism
MH  - Hypoglycemic Agents/*administration & dosage/*pharmacology
MH  - Injections, Intraventricular
MH  - Insulin Resistance
MH  - Male
MH  - Memory/drug effects
MH  - Mice, Inbred C57BL
MH  - Molecular Targeted Therapy
MH  - Neuronal Plasticity/*drug effects/*genetics
MH  - PPAR gamma/*agonists/metabolism/*physiology
MH  - Rosiglitazone
MH  - Thiazolidinediones/*administration & dosage/*pharmacology
OTO - NOTNLM
OT  - Cognitive deficits
OT  - Diabetes
OT  - Insulin resistance
OT  - Peroxisomal proliferator activating receptor
OT  - Synaptic plasticity
EDAT- 2014/12/17 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/17 06:00
PHST- 2014/03/28 00:00 [received]
PHST- 2014/08/25 00:00 [revised]
PHST- 2014/09/27 00:00 [accepted]
PHST- 2014/12/17 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0197-4580(14)00634-4 [pii]
AID - 10.1016/j.neurobiolaging.2014.09.028 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2015 Mar;36(3):1451-61. doi: 
      10.1016/j.neurobiolaging.2014.09.028. Epub 2014 Oct 2.