If you have ever witnessed someone with Parkinson’s disease suffering from tremors, it is a heartbreaking experience. To see someone trapped in a body they cannot control, unable to do anything but ride out the tides of tremors with no relief in sight, is absolutely gut-wrenching. It is difficult to imagine one day having a body that you cannot control, but for many, this becomes a reality as they age. Parkinson’s disease is the second most common neurodegenerative disease, with Alzheimer’s being the most common. It is characterized by a loss of motor control due to degeneration of dopaminergic neurons in the substantia nigra. This results in impaired motor functions that include: rigidity, tremors, bradykinesia (slowness of movement), as well as gait and postural changes. In addition to motor deficits, non-motor symptoms are also present in Parkinson’s, though research in this area is minimal.The presence of non-motor symptoms may come as a surprise due to the emphasis on motor deficits in PD. Less is known about the pathology of non-motor symptoms, but they can precede motor symptoms of PD by many years. Non-motor symptoms include: sensory abnormalities, autonomic dysfunction, cognitive decline, sleep disturbance, and depression. The frequency of non-motor symptoms increases with the severity of Parkinson’s, and they affect all PD patients.
In Parkinson’s disease, neuronal death occurs in various regions of the brain, not just the substantia nigra (the location of dopamine). The affected brain regions are pictured in the image above. Dopamine is the neurotransmitter involved in motor control and reward-motivated behavior. Degeneration of the non-dopaminergic areas of the brain is believed to be implicated in the onset of non-motor symptoms.
Here is a brief summary of the roles of the brain regions that degenerate in PD:
Substantia nigra: comprised of two parts, pars compacta and pars reticulata. The pars reticulata conveys signals to other brain structures. The pars compacta, the region that degenerates in PD, supplies dopamine to the striatum.
Non-dopaminergic Brain areas
Primary motor cortex: contains upper motor neurons that mediate planning and initiation of complex voluntary movements, receives input from substantia nigra
Locus coeruleus: largest group of of neurons involved in synthesis of norepinephrine, modulates circuits involved in attention, memory, emotion, stress, arousal, as well as posture and balance
Raphe nuclei: releases serotonin in the brain, helps regulate motor, somatosensory, and limbic systems
-low serotonin levels found in depression, damage to this area could be linked to depression observed in PD
Thalamus: involved in sensory perception and motor function regulation, receives sensory signals and projects them to the cortex, controls sleep and wake states
-degradation of this area impacts cognition, awareness, and perception
Amygdala: plays a role in processing memory and emotion
Hippocampus: involved in consolidation of information from short-term to long-term memory as well as spatial navigation
The presence of Lewy bodies is another defining characteristic of PD. Lewy bodies are abnormal protein clumps that aggregate in diseased neurons in PD. They are composed primarily of the alpha-synuclein protein, along with other proteins such as ubiquitin and tau. Lewy bodies build up inside the neuron and displace other parts of the cell, leading to cell death. Lewy bodies are found in the brain stem and deplete dopamine levels, and eventually spread to the other brain areas listed above.
Treatment of Parkinson’s disease is extremely difficult due to the complex pathology involved. Genetic mutations, excess glutamate, oxidative stress, and mitochondrial dysfunction are all contributing factors to neurodegeneration in PD.
The most common treatment of PD is the administration of L-Dopa, the precursor of dopamine, in an attempt to increase dopamine levels to help control tremors. It does help, but unfortunately, L-Dopa is not a cure-all. It cannot prevent neurodegeneration, and has averse side effects that include: nausea, hallucinations, confusion, extreme emotional states (especially anxiety), and insomnia, further exacerbating non-motor symptoms. We need more research into the pathology and onset of non-motor symptoms of Parkinson’s disease, as they often precede motor symptoms. Research into the pathology of non-motor symptoms is a viable outlet that could lead to new neuroprotective treatment strategies for Parkinson’s disease in the future.
This post was written in response to an article read and discussed in the Neurochemistry class at Concordia college.
The article can be found here: http://www.ncbi.nlm.nih.gov/pubmed/23380027
PD Brain pathology image retrieved from: http://stepsys.files.wordpress.com/2013/11/parkinsons-disease-204114724_std.jpg
Lewy body image retrieved from: http://www.cumc.columbia.edu/publications/in-vivo/Vol1_Iss19_nov20_02/img/LewyBody.jpg
