Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. The symptoms of schizophrenia are classified into positive, negative and cognitive symptoms. New receptor targets and drugs have being evaluated for addressing the multifaceted syndrome of schizophrenia. is a chronic and disabling mental illness affecting millions of people worldwide. The symptoms of schizophrenia are classified into positive, negative and cognitive symptoms. New receptor targets and drugs have being evaluated for addressing the multifaceted syndrome of schizophrenia.

1. EFFECT OF PTEROSTILBENE ON KETAMINE
INDUCED SCHIZOPHRENIA IN MICE
M.PHARM PROJECT PRESENTATION
BY
DEVENDER.P
HT NO: 12H61S0103
Under the supervision of
Dr. PRAKASH V DIWAN, Ph.D.,FRSC (London)
Professor & Director

2. Introduction
 Schizophrenia is a chronic debilitating multifactor
disorder of mind with a constant prevalence of 1-2% in
the population.
 The rate ratio for males:females was 1.4:1
 It is characterized by Positive, Negative and cognitive
symptoms.

3. Pathophysiology
 The origin is multifactorial with genetic, environmental
and neurotransmitter pathophysiologic components.
 The most influential and plausible are the hypotheses:
 DOPAMINE HYPOTHESES
 GLUTAMATE HYPOTHESES

4. Aim and Hypothesis
 Aim of this study is to investigate the effects of
pterostilbene on the behavior of mice and oxidative stress
under the influence of Ketamine induced schizophrenia
model.
 The hypothesis is that pterostilbene protects from
schizophrenia by acting on GSK3β signaling pathway and
rescues ketamine induced behavioural changes and
oxidative stress.

5. Review of literature
 Yue Hou,Guanbo Xie et All.2014. Pterostilbene attenuates
lipopolisaccharide-induced learning and memory impairment possibly via
inhibiting microglia activation and protecting neuronal injury in mice.
 Dennis K. Miller, Clark E. Oelrichs, et al., 2013. Repeated resveratrol
treatment attenuates methamphetamine-induced hyperactivity and
[3H]dopamine overflow in rodents.
 Jaewon chang,agnes rimando et all.2012. Pterostilbene is a potent
neuromodulator in aging and Alzheimer's disease
 Md. Al Rahim, Agnes M. Rimando et all.2013. Anxiolytic Action of
Pterostilbene: Involvement of Hippocampal ERK Phosphorylation.
 Kuhushwant S.Bhullar and H.P.Vasantha Rupasinghe 2013. Polyphenols:
Multipotent Therapeutic Agents in Neurodegenerative Diseases.

6.  Denise McCormack and David McFadden et all.2013. A Review of
Pterostilbene Antioxidant Activity and Disease Modification .
Peng Zhao,Shang-Ke chen et all 2013.The molecular basis for the
inhibition of phosphodiesterase-4D by three natural resveratrol analogs.
Isolation, molecular docking, molecular dynamics simulations, binding free
energy, and bioassay.
Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, et al.
Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in
aging and Alzheimer's disease.
Ming-Huan Chan, Pao-Hsiang Chiu et al., 2012. Inhibition of glycogen
synthase-3 attenuates psychomimetic effects of ketamine.
Yue Hou, Hongli Zhang et al., 2013. Neuronal injury, but not microglia
activation, is associated with ketamine-induced experimental schizophrenic
model in mice.

7. Materials & Methods
Animals- Swiss Albino Mice
(Protocol. No:I/IAEC/LCP/003/2014/SM/30)
Inducing agent-Ketamine (50mg/kg,i.p)
Test drug – Pterostilbene(10,20mg/kg p.o) from 8th day
to 14th day.
Others: Ellman’s reagent, TCA, pyrogallol, Acetyl
thiocholine iodide,Thiobarbituric acid, CMC.

8. Experimental design
GROUP TREATMENT
Group I: Vehicle control(CMC 0.5%, p.o)
Group II: Negative Control(ketamine 50mg/kg, i.p only)
Group III: Low dose group [ketamine(50mg/kg, i.p ) +
pterostilbene(10mg/kg, p.o)]
Group IV High dose group [ketamine(50mg/kg, i.p ) +
pterostilbene(10mg/kg, p.o)]

9. Behaviour Parameters Assessed
• Locomotor activity by Actophotometer
• Spatial working memory by Y-maze task
• Forced swimming test
• exploratory behaviour by open field habituation task

10. Biochemical Parameters Assessed
• Estimation of Brain Acetylcholinesterase
• Estimation of Brain Thiobarbituric acid reactive species
(TBARS)
• Estimation of Brain Nitrite
• Estimation of Reduced Glutathione (GSH)
• Estimation of catalase
• Estimation of superoxide dismutase

11. STATISTICAL ANALYSIS
 All data are presented as Mean ±S.E.M of 6 animals. The
significance of difference among the groups were assessed
using one way analysis of variance(ANOVA) followed by
Tukey’s test using Graph pad PRISM software and p< 0.05
was considered significant.
 Superscript symbols represent the statistical significance:
 ***p<0.001,**p<0.01, *p<0.05 indicates comparison of negative
control group with control group.
 ###p<0.001, ##p<0.01, #p<0.005 indicates comparison of low
dose group with negative control.
 $$$p<0.001, $$p<0.01 $p<0.05 indicates comparison of high
dose group with negative control.

12. Effect of pterostilbene on Locomotor activity,
Y-maze task

13. Effect of pterostilbene on Open field habituation,
Forced swimming test

14. Effect of pterostilbene on AchE,Nitrite,TBARS

15. Effect of pterostilbene on GSH,CAT,SOD

16. CONCLUSION
• Schizophrenia is a chronic and disabling mental
illness affecting millions of people worldwide. The
symptoms of schizophrenia are classified into
positive, negative and cognitive symptoms. New
receptor targets and drugs have being evaluated for
addressing the multifaceted syndrome of
schizophrenia.
• The results suggest that the drug pterostilbene could
be a new third-generation therapeutic agent for
treating schizophrenia.

17. Referencess
• Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, et al. Low-dose
pterostilbene, but not resveratrol, is a potent neuromodulator in aging and
Alzheimer's disease. Neurobiol Aging 2012;33(9):2062–71.
• Chatterjee M, Ganguly S, Srivastava M, Palit G. Effect of ‘chronic’ versus ‘acute’
ketamine administration and its ‘withdrawal’ effect on behavioural alterations in
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levels in the rat brain as a function of time after drug administration.Revista
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• Harshalkumar Mahajan and Shrikant Pawar. In vivo antimanic activity of lithium
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20. THANK YOU

21. Effect of pterostilbene on Biochemical
estimations
Group GSH
(U/mg protein
Catalase
(U/mgprotein)
SOD
(U/min/mgprot
ein)
TBARS
(nmol/mg
protein)
AchE
(µmol/min/mg
Tissue Nitrite
(µg/mg protein)
Group
I(Vehicle)
0.19±0.02 0.16 ±0.02 22.82±2.06 3.41±0.31 1.64±0.27 3.85±0.26
GroupII(KET
50 mg/kg)
0.02±0.00*** 0.07±0.00* 1.59±0.19*** 5.22±0.55* 6.82±0.17 *** 5.47±0.25**
GroupIII(PTR1
0mg/kg+KET)
0.11±0.01# 0.15±0.01# 12.87±0.94### 5.12±0.42# 3.69±0.19### 4.02±0.24##
GroupIV(PTR2
0mg/kg+KET)
0.17±0.02$$$ 0.16±0.02$ 20.35±2.02$$$ 3.25±0.36$ 2.25±0.26$$$ 3.63±0.25$$$

22. Effect of pterostilbene on Behavioural
parameters
Group Locomotor
activity
Y-Maze task
Line crossings Pokings
FST
Group I(Vehicle) 115.40±6.13 35.22±3.20 106.70±4.41 13.86±1.88 33.33±3.18
Group II (KET 50
mg/kg)
348.30±35.57*** 15.53±3.24** 187.30±17.17*** 49.00±3.49*** 71.67±3.20 ***
GroupIII(PTR
10mg/kg+ KET)
185.70±29.59### 31.68±2.47# 121.30±5.93### 24.15±2.09### 54.00±2.40##
GroupIV(PTR
20mg/kg+ KET)
125.50±9.94$$$ 44.15±4.51$$$ 97.83±3.62$$$ 10.43 ±0.57$$$ 29.67±3.91$$$