Parkinson’s Disease. Parkinson's disease belongs to a group of conditions called movement disorders. Commons symptoms of Parkinson’s disease include:

Parkinson’s Disease

Parkinson's disease belongs to a group of conditions called movement disorders.

Commons symptoms of Parkinson’s disease include:

Tremors, starting in the hands.

Slowed motion (bradykinesia).

Rigid muscles.

Impaired (stooped) posture and balance.

Loss of automatic movements.

Speech changes.

Dementia.

What is Parkinson’s Disease?

Statistical Analysis

“Emerging Trends.” Menopausal Health. American Nurses Association. 2001. Web. 27 Oct. 2010.

Statistical Analysis

Van Den Eeden, Stephen K., and Tanner, Caroline M. “Incidence of Parkinson’s Disease: Variation by Age, Gender, and Race/Ethnicity.” American Journal of Epidemiology. Volume157, Issue11, Pp. 1015-1022. (2003). Web. 27 Oct. 2010.

Dopamine: Happy Juice

Dopamine = catecholamine neurotransmitter

Dopamine is also a neurohormone released by the hypothalamus.

Dopamine is available as an intravenous medication acting on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure.

Production of Dopamine

Connections between low norepinephrine levels and dopamine levels

Connections between low norepinephrine levels and dopamine levels1. Dopamine is a precursor to both Catecholamines,

Norepinephrine and Epinephrine.

2. Dopamine + Dopamine Beta Hydroxylase & Vitamin C -> Norepinephrine

3. Norepinephrine + Phenylethanolamine N-Methyltransferase & S-Adenosyl Methionine with Cortisol -> Epinephrine

DBH

PNMT

Vit. C

Dopamine

Norepinephrine Cortisol SAMe

Epinephrine

Connections between low norepinephrine levels and dopamine levels

Dopamine + Dopamine Beta Hydroxylase (DBH) & Vitamin C -> Norepinephrine

DBHDopamine

Vitamin C

Norepinephrine

Vitamin C is a required cofactor to assist DBH.

DBH is one of a few membrane bound enzymes. Norepinephrine and epinephrine are synthesized in a vesicle.

Connections between low norepinephrine levels and dopamine levels

Norepinephrine + Phenylethanolamine N Methyltransferase (PNMT) & S-Adenosyl Methionine (SAMe) with Cortisol -> Epinephrine

PNMT

SAMe

Cortisol

Norepinephrine Epinephrine

Phenylethanolamine N Methyltransferase converts Norepinephrine (NE) to Epinephrine (Epi) SAMe is a required cofactor in the reaction and

Cortisol positively assists PNMT in this conversion

Dopamine-Motor Control

-Lack of Dopamine => Loss of motor activity

Norepinephrine/Epinephrine-Excitatory Neurotransmitters / Hormones

-Increase heart rate-Increase fight or flight response-Increase awareness and alertness

Connections between low norepinephrine levels and dopamine levels

Why do we care about low levels of norepinephrine?

Norepinephrine (NE)

Released in the body as a Hormone and Neurotransmitter

Hormone functions:

Released by the adrenal medulla along with epinephrine

Released by the brain during a time of stress (i.e. “fight-or-flight”

Levels increase during exercise to cause increase in many different bodily functions

Transported along the same pathway as dopamine

Vasoconstriction

Neurotransmitter functions:

Released by the Autonomic Nervous System (ANS)

Released by most sympathetic postganglionic axons

Adrenergic receptors (α and β) bind to NE that target organs respond to

Can have excitatory or inhibitory effects

Relation to Parkinson’s Disease

Disease effects nerve endings, which produce NE as a neurotransmitter

One study found degeneration of nerve endings in brain that released NE which caused a decrease in BP when patient goes to stand up (NINDS, 2010)

It also found that out of the 29 patients tested, ALL showed a decreased number of NE releasing nerve endings in the heart (NINDS, 2010)

Loss of NE causes a loss of sympathetic nerve terminals in the heart

These NE neurons modulate the dopamine release substantia nigra neurons (Michael J Fox Foundation)

Without NE, the dopaminergic cells produce dopamine but can’t release it causing the symptoms of Parkinson’s (Michael J Fox Foundation)

Lewy Body

History and Research

Alpha-Synuclein

Lewy Body Formation

Effect of PD on motor activity

Motor circuitBasal ganglia

Primary motor cortex

Deterioration of dopamine producing neurons

Decreased amount of dopamine

Increased activity of basal ganglia

Image: Obeso et al

Effect of PD on motor activity

Images: WM Commons, Mikael Häggström

Effect of PD on motor activity

Overactivity of basal ganglia leads to the motor symptoms of the disease

Persistent tremor at rest

Forward-bent walking posture

Shuffling gait

Stiff facial expression

Dyskinesia

Treatment Methods for Parkinson’s Disease

Alter Dopamine LevelsDopamine levels can be increased by using L-Dopa (levodopa in drug terms)(Medications).

The levodopa is combined with carbidopa or benzerazide to allow transport to the brain (Medications).

The L-Dopa will then be converted to dopamine

Treatment Methods

Problems with L-Dopa TreatmentL-Dopa can still be converted to Dopamine outside the brain.

Due to COMT (Catechol-o-methyltransferase) enzyme.

There are two forms, one is in the brain and the other is in the liver, kidneys, and blood (COMT).

COMT inhibitors are used to increase levodopa that gets to the brain.

Side effects include involuntary movements, nightmares, hallucinations, and changes in blood pressure (David)

Dopamine AgonistsMolecules that stimulate dopamine receptors (Medications).

Pramipexole dihydrochloride

Ropinirole Hydrochloride

Bromocriptine

Pergolide

Treatment Methods

Dopamine

Figure Source: www.chemexper.com

Treatment Methods

Deep Brain ShockingTiny electrodes (aka neurostimulator) placed in the basal ganglia

This area is stimulated to block involuntary movements and tremors (NINDS).

Not a cure, but suppresses symptoms

http://www.youtube.com/watch?v=KDjWdtDyz5I

Source: biomed.brown.edu

Treatment Methods

Lewy BodiesTreatment typically includes using a neuroleptic to reduce the symptoms of hallucinations and depression (Jocelyn).

Neuroleptics are tranquilizers

Tranquilizers suppress the CNS.

Counteracts Parkinsons medications

Treatment Methods

Non-Medicinal TechniquesRelieving stress helps healing process (David)

Make daily tasks more simple

Physical therapy

Occupational therapy

Adding handicap features in the house

Small clothing changes

Support Groups

Treatment Methods

Further ResearchNeed to find a way to eliminate lewy bodies without suppressing CNS.

Perhaps ways to reconstruct damaged brain cells using stem cells (Current Research).

Citations

Online Medical Library. Aug 2007. Web. 27 Oct 2010. Dopamine and Agonists Figures. ChemExperChemical Directory. www.chemexper.com. ChemExper Inc. 2010. Web. 27 Oct. 2010. Garrett Reginald and Charles Grisham. Biochemistry. Canada: Brooks/Cole, 2010. Print. Jocelyn, Robert, and Jeanne Segal. Lewy Body Dementia. www.helpguide.org. Helpguide. June 2010. Web. 27 Oct. 2010 Medications Used to Treat Parkinson’s Disease. www.ehealthmd.com. Health Information Publications. 2004. Web. 27 Oct. 2010.NINDS Deep Brain Stimulation for Parkinson’s Disease Information Page. www.ninds.nih.gov. National Institutes of Health. 14 Jun 2010. Web. 27 Oct. 2010.

Neurotransmitter Bios.” Neurorelief. Neuroscience, Inc. n.d. Web. 27 Oct. 2010.Powers, Scott; Howley, Edward. Exercise Physiology: Theory and Application to fitness and performance.

McGraw Hill, 2009. Print.Mosely, A. D. and Romaine, D. S. 2010. The Encyclopedia of Parkinson’s Disease. USA: Hermitage Publishing. Polymeropoulos, M. H. et al. 1997. Mutation in the α-synuclein gene indentified in families with Parkinson’s disease. Science 276: 2045-2047. Baba, M. et al. 1998. Aggregation of α-synuclein in Lewy Bodies of sporadic Parkinson’s disease and dementia with Lewy Bodies. Amer. J. Path. 152: 879-884.Lippa, C. F. et al. 1998. Lewy Bodies contain altered α-synuclein in brains of many familial Alzheimer’s disease patients with mutations in presenilin and amyloid precursor protein genes. Amer. J. Path. 153: 1365-1370.

Citations Continued

“Emerging Trends.” Menopausal Health. American Nurses Association. 2001. Web. 27 Oct. 2010.

Polymeropoulos Mihael H., and Lavedan Christian. “Mutation in the -Synuclein Gene Identified in Families with Parkinson's Disease.” Science. 27 June 1997: Vol. 276. no. 5321, pp. 2045 - 20471 May 2009.

DOI: 10.1126/science.276.5321.2045. 27 Oct. 2010

Medications Used to Treat Parkinson’s Disease. www.ehealthmd.com. Health Information Publications. 2004. Web. 27 Oct. 2010.

COMT. http://ghr.nlm.nih.gov. Genetics Home Reference. Sept 2007. Web. 27 Oct. 2010.

Oboeso, J.A. et al. "Functional Organization of the Basal Ganglia: Therapeutic Implications for Parkinson’s Disease." Movement Disorders. 23. S3 (2008): S548-S559.

Marieb, Elaine N, and Katja Hoenh. Human Anatomy & Physiology. San Francisco, CA: Pearson Education, 2007.

Deep Brain Stimulation Figure. biomed.brown.edu. Brown University. Web. 27 Oct 2010. COMT. http://ghr.nlm.nih.gov. Genetics Home Reference. Sept 2007. Web. 27 Oct. 2010. David Eidelberg M.D. and Michael Pourfar M.D. Parkinson’s Disease. www.merck.com. Merck Manuals.

Ebadi, M. S. 2005. Parkinson’s Disease. USA: CRC Press.

Olanow, C. W., Perl, D. P., DeMartino, G. N., and McNaught, K. P. 2004. Lewy-body formation is an aggresome-related process: a hypothesis. Lan. Neur. 3: 496-503.