We are starting another topic today, and I will be discussing Parkinson's disease in this post. I am sure you must have heard about Parkinson's disease, so I will be explaining it extensively in this post. For a very simple overall definition and overview of Parkinson's disease, it is regarded as a progressive degeneration of the dopaminergic neurons within the substantia nigra leading to altered motor movement. In more simple words, Parkinson's disease is a progressive neurological disorder that affects movement.
Parkinson's disease in patients are accompanied by signs and symptoms such as tremors which is the shaking of hands, and for Parkinson's, there is a specific one known as pill rolling tremors, patients also experience Rigidity where there is a stiffness in the limbs of the patients (Lead-pipe rigidity common in the lower limbs, and cogwheel rigidity common in the upper limbs), they also experience Akinesia which is the loss of motor movement, and pastoral instability. patients with Parkinson's disease usually have an expressionless face as a result of Akinesia..
In the central nervous system, the (Putamen, the Globus Pallidus Extenus, Globus Pallidus Internus) collectively known as the lentiform nucleus, and Caudate Nucleus are the basal ganglia that would be discussed, also we would be discussing the subthalamus, and the substantia nigra as we continue. Let's explain the actual activity of motor movement in the cortex. When there is a thought to perform a movement or cognitive activity it originates from the prefrontal cortex where it could stimulate the premotor cortex, and other parts of the grey matter in the cortex which includes the primary somatosensory cortex, and the primary motor cortex. ,. The motor cortex cell body sends the message to the Putamen in a pathway known as the corticostriatal pathway, released through the glutamate transmitter releasing glutamine into the neuron which is an excitatory neurotransmitter initiating Excitatory Postsynaptic Potential (EPSP) which action potentials which go to the Globus Globus Pallidus Internus which releases Gamma Aminobutyric Acid (GABA), an inhibitory neurotransmitter, causing Inhibitory Postsynaptic Potential (IPSP). The pallidothalamic neuron connects the Globus Pallidus Internus to the thalamus. . There is little action potential from the Globus Pallidus Internus to the thalamus which then sends a stimulatory message to the primary motor cortex then to the muscles, in a pathway known as the Direct pathway.,.
Also, a neuron from the cortex releases glutamine through glutamate receptors to the Putamen which binds to GABAergic neuron causing action potentials that then goes to the Globus Pallidus Extenus. In the Globus Pallidus Extenus, GABA is released. The neuron in the Globus Pallidus Extenus extend to the Subthalamus and since GABA inhibits the neuron, it produces less action potential down the axon subthalamus releasing less GABA, causing fewer IPSPs and more EPSPs. From the subthalamus, the axons move to the Globus Pallidus internus, releasing glutamate which stimulates the GABAergic neuron which stimulates the action potential along the axons of the neuron in the Thalamus, releasing a lot of GABA, causing IPSP inhibiting neurons in the thalamus releasing less action potentials going to the cerebral cortex which will cause an inhibitory process of movement. This process is known as an indirect pathway.,,. Both direct and indirect pathways (stimulatory and inhibitory pathways) are needed because for one part of the body to contract in movement, the opposite side has to relax, and both pathways are responsible for this.
In the Subtantia nigra is the dopaminergic neuron which synapses with the D1 and D2 receptor neurons in the putamen. Dopamine in the direct pathway stimulating the D1 neuron causing lots of action potential releasing more GABA, causing more inhibitory input in the Globus Pallidus Intenus, which will lead to the release of less GABA to the Thalamus causing more effect which is sent to the primary cortex causing more intense frequent action potential causing more effect with contraction. When it goes to the D2 neuron in the putamen which is the neuron for the indirect pathway, dopamine with inhibit the neuron causing less action potential toward the Globus Pallidus Extenus, leading to less GABA, this would continue down in the indirect pathway I wrote above putting intense on whatever action potential is exhibited, and causing a stimulation to the cortex. ,,.
With Parkinson disease, if there is damage to the dopaminergic neuron in the substantia nigra Pars compacta, there will be a decrease in the dopamine released to the GABAergic neuron. With less dopamine released to the D1 neuron, there will be less stimulatory output, causing the action potentials from the putamen to the Globus Pallidus Internus to reduce. With less action potential, there will be less GABA released in the Globus Pallidus Internus, which will lead to less inhibitory postsynaptic potential in the neuron causing an increase in potential towards the thalamus releasing GABA to the GABA inhibitory neurons in the Thalamus which lead to a decreased action potential toward the cerebral primary motor cortex which will send signals via its neurons to synapse within the neuron of the ventral gray horn, causing the cell body through the alpha motor to innervate the skeletal muscle for attraction, and in the case of a decreased action potential as a result of a decreased dopamine, there will be less impulse. If this also happens to the indirect pathway, it would release less dopamine causing less inhibitory input, causing higher action potentials from the putamen releasing more GABA, and causing fewer action potentials through the Axons of the Globus Pallidus Extenus which would lead to more GABA production in the subthalamus, increasing the action potentials being sent to the Globus Pallidus Intenus which would stimulate more action potential releasing more GABA in the Thalamus, which would cause a decrease in the action potentials towards to cortex. Causing a decrease in the input going to the muscle, leading to Akinesia or Bradykinesia, and mask face. With Parkison's disease, dopamine reduces, and the cholinergic neuron causes an increase in acetylcholine, and the instability of both causes Tremors and rigidity. ,,.
Conclusion
In this post, I have been able to explain the pathophysiology of Parkison's disease. In my next post, I will be looking at the Theoretical causes of Parkison's disease, and the drugs to treat Parkison's disease. Thanks for reading, see you in my next post.
Image Citation
Image 1 || Wikimedia commons || Blausen 0704 ParkinsonsDisease