Parkinson's Disease: Pathophysiology and Experimental models

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, leading to motor symptoms such as tremors, rigidity, and bradykinesia. The pathophysiology involves oxidative stress, mitochondrial dysfunction, neuroinflammation, and abnormal protein aggregation, particularly of α-synuclein. Experimental models of PD include in vivo animal models, such as those induced by neurotoxins like MPTP and 6-OHDA, which mimic dopaminergic neuron degeneration. Genetic models using transgenic animals target mutations linked to PD, such as in the SNCA and LRRK2 genes. These models, along with in vitro systems, help elucidate disease mechanisms and provide platforms for testing potential therapeutic interventions.

1. PARKINSON’S DISEASE (PD) By: VAIDEHI VADHVANA Ph.D. Scholar

2. Parkinson's disease  ( PD ), or simply  Parkinson’s ,  is a  long-term   degenerative disorder  of the  central nervous system  that mainly affects the  motor system .  2

3. PD has burst into the public consciousness in recent years. It is a neurodegenerative (the breakdown of brain neurons) disease with the resultant effect of a movement disorder.  3

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6. Causes of PD: The cause of PD is  unknown , with both  inherited  and environmental factors being believed to play a role. Other risk factors are those who have been exposed to certain  pesticides  and who have prior  head injuries .  Coffee  drinkers,  tea  drinkers, and  tobacco smokers  are at a reduced risk. 6 6

7. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are  tremor ,  rigidity ,  slowness of movement , and  difficulty with walking . Symptoms

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11. Facts about Parkinson’s Parkinson’s Disease Is Incurable Having Parkinson’s Is Not a Death Sentence  The Disease Is Unique in Every Person Non-Motor Symptoms Can Be More Detrimental Parkinson’s Can Increase the Risk of Depression Not Everyone With Parkinson’s Experiences Tremors (30% do not have tremors)

12. Parkinson’s disease is unpredictable, so it can be difficult to make any plans—big or small—without worrying need to cancel at the last minute. Living with the painful symptoms, both physical and mental, can be draining. A person with Parkinson's will have to put much more effort and time into each task and may not be able to drive at all. 12

13. PATHOPHYSIOLOGY OF PD 13

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17. 18 The part of the brain most affected is the basal ganglia , and the prime culprit is dopamine deficiency that occurs in this brain region. Why not add back dopamine? Actually, this is the mainstay of medical treatment, but eventually the neurons themselves break down, and the medication becomes less effective.

18. IS THERE HOPE?? Yes , in the form of medications and deep brain stimulatory surgery, but also with lifestyle modifications. Lifestyle factors include iron, vitamin D  19

19. EXPERIMENTAL MODELS 20

20. Tremors: Tremorine (25 mg/kg I.P), oxo- tremorine (500 ug/kg I.P) etc. Less frequently, amine & nicotine is used. Catatonia ( abnormal movements ): Chlorpromazine (10mg/kg I.P), Reserpine (2.5 to 5 mg/kg I.P), Haloperidol (200 ug/kg I.P), Perphenazine (5 mg/kg I.P) 22

21. Effect of test drug on Oxo- tremorine induced tremors Oxo- tremorine : Powerful stimulant in CNS. Cholinergic system Results in tremors, head twitches, ataxia, lacrimation, salivation and diahorrea . Anti-Parkinson drugs: Inhibit the above symptoms. 23

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24. Effect of test drug on brain lesion induced tremors Brain lesion  Substantia nigra  Parkinsonism develops. Brain lesion  Stereotaxic method  6 hydroxy dopamine. Anti-Parkinson drug  Suppress brain lesion effects. 26

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30. Ayurveda Drugs Atmagupta / Kapikacchu , Sahchar Sahacharadi Vati , Nakula taila 32

31. THANK YOU