PMID- 25547373
OWN - NLM
STAT- MEDLINE
DCOM- 20151204
LR  - 20181113
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 388
IP  - 3
DP  - 2015 Mar
TI  - Synergistic effects of GSK-3beta and HDAC inhibitors in intracerebroventricular 
      streptozotocin-induced cognitive deficits in rats.
PG  - 337-49
LID - 10.1007/s00210-014-1081-2 [doi]
AB  - Recent studies suggest the importance of combined treatment of glycogen synthase 
      kinase-3beta (GSK-3beta) and histone deacetylase (HDAC) inhibition in various in vitro 
      and in vivo models of neurological diseases. Lithium chloride (LiCl) and 
      valproate (VPA), two well-known mood stabilizers, have been reported to act 
      through GSK-3beta and HDAC inhibition, respectively. The present study was designed 
      to investigate the potential of low-dose combination of LiCl and VPA in 
      intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive deficits in 
      rats. STZ was injected twice (3 mg/kg ICV) on alternate days (day 1 and day 3) in 
      rats. The ICV-STZ-treated rats received LiCl (60 mg/kg, i.p.), VPA (200 mg/kg, 
      i.p.), and combination of both LiCl (60 mg/kg, i.p.) and VPA (200 mg/kg, i.p.) 
      drugs for a period of 3 weeks. The ICV-STZ administration results in significant 
      memory impairment, elevated oxidative-nitrosative stress, and reduced 
      brain-derived neurotrophic factor (BDNF) levels. Using a battery of behavioral 
      and biochemical tests, we observed that co-treatment of both drugs showed 
      synergistic effect in improving the spatial learning and memory impairment as 
      well as significantly attenuated the oxidative stress markers in STZ-treated rats 
      as compared to either drug alone. Moreover, the combination of both drugs 
      reversed the hyperinsulinemic brain condition and improved the BDNF levels in 
      STZ-treated rats. Based upon these results, it could be suggested that a low-dose 
      combination of LiCl and VPA produces synergistic and more consistent 
      neuroprotective effects in ICV-STZ-induced cognitive deficits in rats.
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
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141231
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 5W494URQ81 (Streptozocin)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - G4962QA067 (Lithium Chloride)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Avoidance Learning/drug effects
MH  - Brain/drug effects/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cognition Disorders/chemically induced/*drug therapy/metabolism/pathology
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Glutathione/metabolism
MH  - Glycogen Synthase Kinase 3/*antagonists & inhibitors/metabolism
MH  - Histone Deacetylase Inhibitors/*therapeutic use
MH  - Insulin/metabolism
MH  - Lithium Chloride/*therapeutic use
MH  - Malondialdehyde/metabolism
MH  - Memory/drug effects
MH  - Memory Disorders/chemically induced/*drug therapy/metabolism/pathology
MH  - Neuroprotective Agents/*therapeutic use
MH  - Nitrates/metabolism
MH  - Nitrites/metabolism
MH  - Rats, Wistar
MH  - Spatial Learning/drug effects
MH  - Streptozocin
MH  - Valproic Acid/*therapeutic use
EDAT- 2014/12/31 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/31 06:00
PHST- 2014/08/07 00:00 [received]
PHST- 2014/12/12 00:00 [accepted]
PHST- 2014/12/31 06:00 [entrez]
PHST- 2014/12/31 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1007/s00210-014-1081-2 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2015 Mar;388(3):337-49. doi: 
      10.1007/s00210-014-1081-2. Epub 2014 Dec 31.