Page 108 - AN-3-4

Advanced Neurology Stress accelerates parkinsonism in rats

motor symptoms characteristic of PD. However, no studies the homeostatic balance or prepare the body for possible
have clarified the relationship between this pathological future imbalances (anticipation). However, excessive
hallmark and various non-motor symptoms of the disease, stress responses can result in deleterious alterations. 18,19
such as cognitive deficits, autonomic dysfunction, anxiety, The response of the body to stress is similar irrespective
sleep impairments, and mood disorders. 4 of whether it is triggered by psychological, environmental,
18
Although the precise mechanisms underlying the loss or physiological stimuli. This response involves the
of dopaminergic neurons in the nigrostriatal pathway are release of vasopressin and corticotropin-releasing
not fully understood, PD is recognized as a disease with a hormone by the hypothalamus, which induces the release
multifactorial etiology. Among several factors, oxidative of adrenocorticotropic hormone by the anterior pituitary,
2,5
stress is believed to be a relevant mechanism in several ultimately leading to the release of glucocorticoids by
neurodegenerative disorders. The central nervous system the adrenal glands. 20,21 In turn, corticosterone (CORT)
6
is particularly vulnerable to oxidative stress due to its higher stimulates glucocorticoid receptors in the hypothalamus
oxygen consumption than other tissues. Furthermore, and pituitary gland to regulate the hypothalamic-
neurons are less proliferative and have higher levels of pituitary-adrenal (HPA) axis through a negative feedback
nitric oxide than other cells. In this regard, the metabolism mechanism. This mechanism is essential to limit the
of nitric oxide is associated with the generation of reactive body’s response to stressors. 17,21 Nevertheless, the stress
oxygen species, which enhances the deleterious effect of response is not confined to the HPA axis alone; there is also
this compound. 6,7 integration among several brain regions. This integration is
facilitated by the activation of the paraventricular nucleus
Mapping studies in patients with familial forms of of the hypothalamus. 20,22
PD using DNA markers have demonstrated a strong
association between the early development of motor signs of Moreover, the mechanisms of oxidative stress are
parkinsonism, such as bradykinesia, resting tremor, muscle implicated in the changes caused by psychophysiological
6,20
rigidity, postural instability, and genetic inheritance. stress in the HPA axis. For instance, mitochondrial
8
However, only 5 – 10% of the cases are familial. The disturbances can cause dysregulation of the enzyme
6,7
primary genes involved in these mechanisms include those NADPH oxidase, which contributes to the release of free
6,23
encoding proteins related to the pathophysiology of PD, radicals in the central nervous system. The generation
such as α-synuclein and parkin. 6,8,9 Most patients present of oxidative stress is related to increased corticotropin-
with the idiopathic form of the condition, which typically releasing hormone and adrenocorticotropic hormone
occurs in people aged >60 years. 2,9 levels, resulting in behavioral changes consistent with
the reaction to psychological stress. As mentioned
24
Stress is among the several factors identified as earlier, oxidative stress is a key feature in both PD and
potential predisposing conditions for the development of psychophysiological stress, emphasizing the importance
neurodegenerative processes. Specifically concerning PD, of investigating the possible relationship between
a case report described that a previously healthy 38-year- psychological stress and the development of this disease. 6
old woman with no history of neuropsychiatric illnesses
presented with resting tremor 1 week after experiencing Overall, the evidence suggests that psychological stress
an acute episode of intense psychological stress, thereby could be a significant predisposing factor for idiopathic PD.
developing early symptoms of PD. Furthermore, a In this context, animal models have been valuable tools for
10
preclinical study showed that the neuroprotective effects investigating several aspects of neurodegenerative diseases,
of physical exercise in rats with experimentally induced including the risk factors for PD. Nevertheless, classical
2
PD were counteracted by exposure to mild stressors. models that induce parkinsonism using neurotoxins
10
Although several studies have suggested an association generally promote acute severe motor impairments,
between PD and psychophysiological stress, 11-14 most making it difficult to evaluate the possible aggravation or
have focused on the relationship between stress and the acceleration of the process. 2,25,26
worsening of cognitive and motor symptoms rather than Repeated administration of a low dose of reserpine,
investigating the possible causal associations. 11,15 which is a blocker of vesicular monoamine transporter 2,
Stress is a physiological response to external and has been proposed as a progressive pharmacological model
2,27
internal disturbances and is useful for the body to adapt of parkinsonism. This protocol induces progressive
to different adverse conditions. 16,17 Stress response can also motor and non-motor signs reminiscent of the disease as
occur in the presence of adverse psychosocial situations well as PD-related alterations in the nigrostriatal pathway.
or due to the cognitive perception of unpredictability. 16,18 These alterations include increased oxidative stress
These processes induce physiological changes that restore (reflected by increased membrane lipid peroxidation),

Volume 3 Issue 4 (2024) 2 doi: 10.36922/an.4037