The Potential Effect of Caffeine and Nicotine Co-administration on the Induction of Alzheimer s disease

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1 The Potential Effect of Caffeine and Nicotine Co-administration on the Induction of Alzheimer s disease

2 Azza A Ali *, Hebatalla I Ahmed * Hanan A Abd El-Samea ** Ebtehal El-Demerdash *** * Pharmacology & Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. ** Pharmacist, Cairo, Egypt. *** Pharmacology & Toxicology Department, Faculty of Pharmacy,Ain Shams University, Cairo, Egypt.

3 Alzheimer s disease Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized clinically by cognitive decline and memory loss It was first described by German psychiatrist and Neuropathologist Alois Alzheimer in 1906

4 Pathological hallmarks of AD

5 Lianne Friesen and Nicholas Woolridge β-amyloid plaques

6 Neurofibrillary tangles

7 Types of AD Early-onset familial AD caused by mutation of genes Late-onset sporadic Alzheimer's disease (LOAD)

8 Aluminum Aluminum is a well established neurotoxin and is suspected to be linked with various neurodegenerative diseases including Alzheimer s disease

9 Exposure to Aluminum Component of dialysis solution Antacids Contamination of drinking water Aluminum Antiperspirants cooking utensils

10 Neurotoxicity of Aluminium Aluminum binds to phosphate groups of DNA RNA DNA topology Affects Expression of genes Induces expression of pro-inflammatory and pro-apoptotic genes Elevated expression of APP Altered expression of oxidative marker genes

11 (Masahiro Kawahara and Midori Kato-Negishi)

12 Caffeine and nicotine are the most commonly co-used psychostimulants

13 Caffeine The most widely consumed psychoactive drug present primarily in coffee and tea.

14 Caffeine is a non- selective A1 and A2 receptor antagonist The blockade of A2A receptors has been found to afford neuroprotection against different brain insults

15 Caffeine acts also by increasing Cortical activity Cerebral energy metabolism Extracellular Ach concentration

16 Antioxidant prevents the neurons from oxidative damage Reduces the risk of chronic degenerative diseases

17 Nicotine A major component of cigarette smoke Has been shown to improve cognitive function in AD patients

18 Nicotine induces its effects by acting on nachr in the hippocampus The brains of AD patients exhibit marked decreases in nachr binding in neocortical and hippocampal regions. Nicotine improves cognitive function in AD patients

19 Nicotine acts also by Increasing the expression of BDNF mrna in the hippocampus Attenuating the impairment of LTP and spatial memory associated with chronic stress Antioxidant effects

20 AIM OF THE WORK Study the behavioral,biochemical, and histopathological changes induced by caffeine or nicotine during induction of AD in rats.

21 Evaluate the influence of caffeine and nicotine co-administration against aluminum-induced AD in rats.

22 MATERIALS AND METHODS

23 Animals Forty male Sprague Dawley rats, weighing g were used.

24 Design of the work Five groups of rats were used and received daily for five weeks 1 Control (Saline) 2 ALCL3.6H2O (70 mg/kg, IP) 3 ALCL3+ Caffeine (5mg/kg, IP) 4 ALCL3 + Nicotine (1mg/kg, SC) 5 ALCL3 + Caffeine + Nicotine

25 1. Behavioral experiments Forced swimming test Morris water maze test Conditioned avoidance test

26 Parameters Immobility score Swimming score Climbing score

27 Parameters Learning ability Memory trial

28 Parameters Numbers of trials performed by rats to avoid the electric shock at 1 st & 2 nd days of the experiment

29 2. Biochemical parameters AchE activity Oxidative stress parameters MDA SOD TAC

30 3. Histopathological examination of the brain

31 RESULTS

32 Forced swimming test Immobility score count/5min Climbing score count/5min 6 a Control Control AlCl3 b AlCl3+Caffeine AlCl3 b AlCl3+Nicotine a,b AlCl3+Caffeine b AlCl3+Caffeine+Nicotine b AlCl3+Nicotine a,b,d AlCl3+Caffeine+Nicotine Swimming score count/5min Control a AlCl3 a,b AlCl3+Caffeine AlCl3+Nicotine AlCl3+Caffeine+Nicotine Significant p<0.05 : a: from control b: from AlCl3 c: from AlCl3 +Caffeine d: from AlCl3 +Nicotine b a,b,d

33 Morris water maze learning ability Significant p<0.05 : a: from control b: from AlCl3 c: from AlCl3 +Caffeine d: from AlCl3 +Nicotine

34 Morris water maze memory trial Time spent in the target quadrant (sec) Control b,c b,c a,d a AlCl3 AlCl3+Caffeine AlCl3+Nicotine AlCl3+Caffeine+Nicotine Significant p<0.05 : a: from control b: from AlCl3 c: from AlCl3 +Caffeine d: from AlCl3 +Nicotine

35 No. of trials to avoid the electric shock Conditioned avoidance test Number of trials to avoid the electric shock Control AlCl3 First day a a,d AlCl3+Caffeine b,c AlCl3+Nicotine b,c AlCl3+Caffeine+Nicotine No. of trials to avoid the electric shock 10 a Control second day AlCl3 a,b,d AlCl3+Caffeine a,b,c AlCl3+Nicotine b,c AlCl3+Caffeine+Nicotine Significant p<0.05 : a: from control b: from AlCl3, c: from AlCl3 +Caffeine d: from AlCl3 +Nicotine

36 Biochemical parameters Acetylcholinestrase ng/g tissue Control AchE activity a a,b,c a,b,d a,b,c,d AlCl3 AlCl3+Caffeine AlCl3+Nicotine AlCl3+Caffeine+Nicotine Significant p<0.05 : a: from control b: from AlCl3 c: from AlCl3 +Caffeine d: from AlCl3 +Nicotine

37 Oxidative stress parameters MDA nmol/g tissue a a,b a,b a,b,c,d SOD U/g tissue a a,b a,b b,c,d 0 0 Control AlCl3 AlCl3+Caffeine AlCl3+Nicotine 60 AlCl3+Caffeine+Nicotine Control a,b,c,d AlCl3 AlCl3+Caffeine AlCl3+Nicotine AlCl3+Caffeine+Nicotine TAC µmol/ g tissue Control a a,b,d a,b,c AlCl3 AlCl3+Caffeine AlCl3+Nicotine AlCl3+Caffeine+Nicotine Significant p<0.05 : a: from control b: from AlCl3 c: from AlCl3 +Caffeine d: from AlCl3 +Nicotine

38 Histopathological alterations Degeneration &pyknosis in hippocampus neurons Eosinophillic plaque formation in striatum Histopathological examination Control ALCL3 ALCL3+Caffeine ALCL3+Nicotine ALCL3+Caffeine +Nicotine _ _ Gliosis _ ++ _ + _ Congestion _ + _ + _ +++ sever ++ moderate + mild - Nil

39 Brain of rat in control group showing normal histological structure of the hippocampus. Brain of rat in ALCL3 group showing neuronal degeneration and pyknosis in hippocampus. Brain of rat in Caffeine and Nicotine co-administration group showing normal histological structure of hippocampus

40 Conclusions

41 Aluminum chloride at dose 70mg/kg for five weeks Impairment of learning and memory Neuronal degeneration in hippocampus AchE & MDA SOD &TAC

42 Effect of Caffeine Protect against neuronal degeneration in hippocampus AchE &MDA SOD&TAC The improvement in memory and learning not appeared in all behavioral tests

43 Effect of Nicotine Improvement in learning and memory AchE &MDA SOD &TAC Histopathological examination still showed mild gliosis in striatum

44 Effect of caffeine and nicotine co-administration More pronounced protecting effect from learning and memory impairment Prevention of neuronal degeneration in the hippocampus AchE &MDA SOD &TAC

45 Co-administration of caffeine and nicotine can reduce the risk of neuronal degeneration in the hippocampus and attenuate the impairment of learning and memory associated with AD

46

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