pH

1. Study of the Possible
Neuroprotective Effect of
Liraglutide on Memory
Impairment in Letrozole-
Induced Polycystic Ovary
Syndrome Model in Rats
Introducti
on
Aim
of
the
Work
Material
and
Methods
Results
Conclusi
on

2. Introducti
on
Aim
of
the
Work
Material
and
Methods
Results
Conclusi
on Muhammad Aser Eltarzy
Teaching assistant of Pharmacology & Toxicology,
Faculty of Pharmacy, Misr University for Sciences and Technology
Presented by
Dr. Rania Mohsen Abd-elsalam
Prof. of Pharmacology & Toxicology
Faculty of Pharmacy, Cairo University
Under the supervision of
Dr. Maha Ali Eissa
Assistant Prof. of Pharmacology & Toxicology
Faculty of Pharmacy, MUST University
Dr. Muhammad Abdullatif
Assistant Prof. of Pharmacology & Toxicology,
Faculty of Pharmacy, Cairo University

3. Introducti
Aim
of
the
Work
Material
and
Methods
Results
Conclusi
on Polycystic ovary syndrome (PCOS) is
the most prevalent endocrine disorder
affecting 7% to 20% of women of
reproductive age
Polycystic ovary
syndrome
The pathological changes of PCOS and
its clinical consequences represents a
higher risk for cardiovascular and
metabolic comorbidities.
It was observed that the brain plays a
main role in both the ontogeny and
pathophysiology of PCOS.

4. Introducti
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on
• Notch proteins and ligands have been
detected in the rodent ovary and are also
continuously present in the nervous
system at particularly high levels in the
hippocampus.
Notch
pathway
• Notch signaling pathway is a highly
conserved ubiquitous signaling system
that plays an essential and well-studied
role in cell-cell communication.
• It was found that Notch regulates learning
and memory and affects the activity of
downstream transcription factors believed
to be involved in memory

5. Introducti
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of
the
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Material
and
Methods
Results
Conclusi
on An acylated analogue of glucagon-like peptide-1
(GLP-1) approved by the FDA to improve
glycaemic control in adults with type 2 diabetes
mellitus
GLP-1 receptors (GLP-1R) are expressed throughout
the central nervous system, playing a central role in the
regulation of neuronal activity and protecting the brain
tissue.
Liragluti
de
Therefore, GLP-1R agonists are promising neuroprotective
agents against brain neurodegeneratective pathologies

6. Introducti
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of
the
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and
Methods
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Conclusi
on
The present study is designed to
investigate the possible
neuroprotective effect of liraglutide on
memory impairment in letrozole-
induced model of polycystic ovary
syndrome in rats and to explore the
underlying mechanisms associated
with any protective effects.

7. Introducti
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of
the
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and
Methods
Results
Conclusi
on
animals 40 Adult female Wistar rats, weighing 180 –
200 g, were used.
Tested
drug
Liragluti
de
(200 µg/kg/day.i.p), dissolved in 0.09%
normal saline
Material

8. Introducti
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of
the
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Material
and
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Conclusi
on
Polycystic ovary
induction
Method
Induced by administration of letrozole (1
mg/kg, p.o) dissolved in 1% CMC in 0.9%
normal saline once daily for 21
successive days.

9. Introducti
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on
Liraglutide
group
GP 3
Letrozole
+Liraglutide
group
GP 4
Letrozole-Induced
PCOS group
GP 2
Control
group
GP 1

10. Introducti
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Conclusi
on 1 21 52 58
Letrozole Liraglutide Behavioral Tests Scarification

11. Introducti
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on
Western Blot RT-PCR ELISA
Hes-1
GLP-1R
PI3K
JNK
Presenilin
-1
Survivin
γ-Secretase
Aβ
Ach
E
Ac
h
NICD
NFκ
B
Insulin
Testosterone
Biochemical Parameters

12. Introducti
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0
1
2
3
4
5
6
CTRL LIR PCOS PCOS+LIR
NICD
(relative
expression) **** ****

13. Introducti
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on
0
1
2
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4
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6
7
8
CTRL LIR PCOS PCOS+LIR
Hes-1
(relative
expression) **** ****

14. Introducti
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on
0
50
100
150
200
250
CTRL LIR PCOS PCOS+LIR
γ-Secretase
(pg/mL) **** ****

15. Introducti
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on
0
2
4
6
8
10
12
CTRL LIR PCOS PCOS+LIR
Presenilin-1
(relative
expression) **** ****

16. Introducti
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on
0
1
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CTRL LIR PCOS PCOS+LIR
Aβ
(pg/mL) **** ****

17. Introducti
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on
0
0.2
0.4
0.6
0.8
1
1.2
1.4
CTRL LIR PCOS PCOS+LIR
PI3K
(relative
expression) **** ****

18. Introducti
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on
0
1
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8
9
CTRL LIR PCOS PCOS+LIR
JNK
(relative
expression) **** ****

19. Introducti
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on
0
0.2
0.4
0.6
0.8
1
1.2
CTRL LIR PCOS PCOS+LIR
Survivin
(relative
expression) **** ****

20. Introducti
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0
50
100
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250
CTRL LIR PCOS PCOS+LIR
NFκB
(ng/mL) **** ****

21. Introducti
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on
0
0.2
0.4
0.6
0.8
1
1.2
CTRL LIR PCOS PCOS+LIR
GLP-1R
(relative
expression) **** ****

22. Introducti
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Conclusi
on
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
CTRL LIR PCOS PCOS+LIR
Insulin
(ng/mL) **** ****

23. Introducti
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on
0
0.5
1
1.5
2
2.5
CTRL LIR PCOS PCOS+LIR
AChE
(mU/ml) **** ****

24. Introducti
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0
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CTRL LIR PCOS PCOS+LIR
Acetylcholine
(ng/mL) **** ****

25. Introducti
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0
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CTRL LIR PCOS PCOS+LIR
Testosterone
(ng/mL) **** ****

26. Introducti
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on
0
5
10
15
20
25
CTRL LIR PCOS PCOS+LIR
Time
spent
in
target
quadrant
(sec) ** ***

27. Introducti
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0
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CTRL LIR PCOS PCOS+LIR
Recognition
index
(%) **** *

28. Introducti
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CTRL LIR PCOS PCOS+LIR
Alternation
(%)
** ns

29. Introducti
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on
CTRL LIR
Histopathological examination of the ovaries
from different groups samples
Both CTRL and LIR showed normal histological structure of the different
stages of follicular maturation, multiple corpus luteum formation

30. Introducti
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Conclusi
on
PCOS
PCOS+LIR
PCOS: multiple follicular cysts
formation
Cyst
PCOS+LIR: normal histological
structure with detection of multiple
corpus luteum formation
Cyst

31. Introducti
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Conclusi
on
CTRL LIR
Histopathological examination of hippocampal region
from different groups samples
Both CTRL and LIR showed normal histological structure of hippocampal
layers with apparent intact neurons

32. Introducti
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Methods
Results
Conclusi
on
PCOS
PCOS+LIR
PCOS: severe nuclear pyknosis and
degeneration in most of the neurons
PCOS+LIR: normal structure with
no histopathological alteration in
hippocampal

33. Introducti
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Conclusi
on
PCOS
• represents a higher risk for cognition impairment as:
1. It caused marked stimulation of inflammatory
and pro-apoptotic pathways.
2. It causes obvious alteration in cognitive functions
measured by some behavioral tests
3. The caused chronic inflammation introduced deterioration
of the hippocampal tissue.

34. Introducti
Aim
of
the
Work
Material
and
Methods
Results
Conclusi
on
Liraglutide
1. It switched off the activated inflammatory and pro-apoptotic
pathways.
• might considered a promising neuroprotective agent as:
2. It improved cognitive functions indicating parameters in
some behavioural tests.
• protected against PCOS attributed pathological changes

35. THANK YOU