Parkinson’s disease (PD) is described as a neurodegenerative disease characterized by akinesia (loss or impairment of voluntary movement), rigidity, tremors and difficulty walking. The clinical symptoms are thought to be mainly caused by the dopaminergic (DA) neurodegeneration, with other neurotransmitters such as serotonin or acetylcholine being partially responsible as well. Neurodegeneration is the deterioration of the nervous system, especially of the neurons in the brain. Some possible causes of PD include viral infection, head trauma, pesticides, and genetic mutation. However, roughly 90% of PD cases are isolated and their causes still remain unknown. One cause that is recognized as being significant is the loss of nigrostriatal dopamine.
In the midbrain there are three main dopamine (a common neurotransmitter) pathways. One is the nigrostriatal pathway that goes from an area in the midbrain called the substantia nigra (SN) to the striatum (STR). The second one is called the mesolimblic pathway which goes from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and other limbic areas. The third one is called the tuberoinfundibular pathway (TIDA) which goes from the arcuate nucleus (AN) to the pituitary gland. Recent studies have shown that physical and/or psychological stress facilitate dopaminergic neurodegeneration, mainly damaged by neurotoxins (toxins that target the nervous system), in the nigrostriatal pathway. A recent study found that chronic restraint stress (RS), without any exposure to neurotoxins, caused significant loss of DA neurons in the SN as early as 2 weeks. This indicates that chronic stress plays a key role in DA damage in the brain. However, it’s not clear what the effects of chronic stress are on the other two pathways, the VTA and TIDA.
This was precisely the goal of the study done by researchers Sugama and Kakinuma in 2016 when they set out to examine the alterations of dopaminergic neurons in the mesolimbic and tuberoinfundibular DA pathways in rats caused by chronic stress for 2-week up to 16-week periods. First they compared the number of TH-immunoreactive (TH-ir) neurons in the VTA between the control rats (no stress) and chronic RS rats. Tyrosine hydroxylase (TH) is the particular enzyme they used to detect dopaminergic loss. They found that there was a significant loss of TH-ir neurons in the VTA in rats that were subject to chronic RS. Numbers decreased by 9.8% by 2 weeks, 19.2% by 4 weeks, 39.5% at 8 weeks and 40.6% by 16 weeks. They then did the same for TH-ir neurons in the TIDA and found the same results: a significant loss of TH-ir neurons in the TIDA for the chronic RS rats when compared with the control rats. Numbers decreased by 10.9% by 2 weeks, 38.2% by 4 weeks, 56.3% by 8 weeks and 57.1% by 16 weeks. In other words, results demonstrated that chronic RS significantly decreased the number of TH-ir cells in both the VTA and TIDA.
However, these results tell another story as well. Depression occurs in 40-60% of patients suffering from PD. The VTA is involved in emotional functions including motivation, reward and desire. Number of neurons in the VTA are decreased in severely depressed individuals. Blocking DA-releasing neurons in the VTA results in depression-like symptoms (eg. loss of motivation). By stimulating the DA neurons in the VTA it causes the depressive behaviors to return. Therefore, it’s possible that the neuronal loss of the VTA following the chronic stress could be related to depression. Although chronic stress is only one of the many possible causes of Parkinson’s disease, it adds to what we know about the disease meaning, hopefully, it adds to the chances we have of preventing it.
Sugama, S., & Kakinuma, Y. (2016). Loss of dopaminergic neurons occurs in the ventral tegmental area and hypothalamus of rats following chronic stress: Possible pathogenetic loci for depression involved in Parkinson’s disease. Neuroscience Research, 11148-55.