PMID- 25391764
OWN - NLM
STAT- MEDLINE
DCOM- 20151224
LR  - 20181113
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 56
IP  - 1
DP  - 2015 May
TI  - Histone deacetylase inhibitor, trichostatin A, improves learning and memory in 
      high-fat diet-induced cognitive deficits in mice.
PG  - 1-11
LID - 10.1007/s12031-014-0461-x [doi]
AB  - Metabolic syndrome is increasingly recognized for its effects on cognitive 
      health. Recent studies have highlighted the role of histone deacetylases (HDACs) 
      in metabolic syndrome and cognitive functions. The present study was designed to 
      investigate the possible therapeutic role of a HDAC inhibitor, trichostatin A 
      (TSA), in cognitive impairment associated with metabolic syndrome. To ascertain 
      the mechanisms involved, we fed mice with high-fat diet (HFD) for 4 weeks and 
      examined changes in behavioral and biochemical/oxidative stress markers. Mice 
      subjected to HFD exhibited characteristic features of metabolic disorder, viz., 
      hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and lower high-density 
      lipoprotein (HDL) cholesterol levels. Moreover, these mice showed severe deficits 
      in learning and memory as assessed by the Morris water maze and passive avoidance 
      tasks along with elevated oxidative stress and inflammatory markers in brain 
      homogenates. The observed changes occurred concurrently with reduced 
      brain-derived neurotrophic factor (BDNF). In contrast, the mice treated with the 
      HDAC inhibitor, TSA (0.5 and 1 mg/kg, i.p.), showed a significant and 
      dose-dependent reduction in serum glucose, triglycerides, and total cholesterol 
      along with improvement in HDL-cholesterol levels and learning and memory 
      performance. TSA treatment also results in alleviation of oxidative stress and 
      neuroinflammatory markers. Moreover, TSA significantly augmented the BDNF levels 
      in HFD-fed mice. Thus, based upon these observations, it may be suggested that 
      HDAC inhibition could be a novel therapeutic strategy to combat cognitive 
      impairment associated with metabolic syndrome.
FAU - Sharma, Sorabh
AU  - Sharma S
AD  - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 
      333031, Rajasthan, India.
FAU - Taliyan, Rajeev
AU  - Taliyan R
FAU - Ramagiri, Shruti
AU  - Ramagiri S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141114
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Triglycerides)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Brain/drug effects/metabolism/physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cholesterol/blood
MH  - Cognition Disorders/*drug therapy/etiology
MH  - Diet, High-Fat/adverse effects
MH  - Histone Deacetylase Inhibitors/pharmacology/*therapeutic use
MH  - Hydroxamic Acids/pharmacology/*therapeutic use
MH  - Male
MH  - *Maze Learning
MH  - *Memory
MH  - Metabolic Syndrome/*drug therapy/etiology
MH  - Mice
MH  - Oxidative Stress
MH  - Triglycerides/blood
EDAT- 2014/11/14 06:00
MHDA- 2015/12/25 06:00
CRDT- 2014/11/14 06:00
PHST- 2014/09/16 00:00 [received]
PHST- 2014/11/03 00:00 [accepted]
PHST- 2014/11/14 06:00 [entrez]
PHST- 2014/11/14 06:00 [pubmed]
PHST- 2015/12/25 06:00 [medline]
AID - 10.1007/s12031-014-0461-x [doi]
PST - ppublish
SO  - J Mol Neurosci. 2015 May;56(1):1-11. doi: 10.1007/s12031-014-0461-x. Epub 2014 
      Nov 14.