Thinking outside the box?

Understanding Parkinson's disease requires delving into the complex interplay of the various neurotransmitters and hormones within the brain. Among these key players are dopamine, γ-aminobutyric acid (GABA), serotonin, dehydroepiandrosterone (DHEA), and cortisol.

Each of these substances contributes to the regulation of motor functions, mood, and stress response, and dysregulation in their levels or signaling pathways has been implicated in the aetiology of Parkinson's disease (PD).

What we already know

At the center of Parkinson's disease lies the dopaminergic system. Dopamine is a neurotransmitter primarily associated with motor control, reward, and motivation. In PD, there is a progressive degeneration of dopamine-producing neurons in the substantia nigra, a region of the brain involved in movement regulation. This neuronal loss leads to a significant reduction in dopamine levels within the basal ganglia, disrupting the delicate balance of neurotransmission essential for smooth motor function. The resulting dopamine deficiency manifests clinically as the cardinal symptoms of PD, including bradykinesia (slowness of movement), rigidity, tremor, and postural instability.

Pushing the envelope slightly

Dopamine is not the only neurotransmitter implicated in PD pathophysiology. GABA, the primary inhibitory neurotransmitter in the brain, also plays a crucial role in modulating motor function. In PD, there is evidence of altered GABAergic transmission within the basal ganglia, contributing to the disruption of motor circuitry. Dysregulation of GABAergic interneurons can exacerbate the imbalance between inhibitory and excitatory signals, further impairing motor control and coordination.

Serotonin, another neurotransmitter with diverse roles in mood regulation, sleep-wake cycles, and cognition, has been implicated in the non-motor symptoms of PD. Serotonergic dysfunction may contribute to depression, anxiety, and cognitive impairment commonly observed in PD patients. Additionally, serotonin modulates the activity of dopaminergic neurons, influencing dopamine release and turnover in the brain. Dysfunction in the serotonergic system may exacerbate dopaminergic deficits, amplifying motor and non-motor symptoms in PD.

It may be useful to test for GABA and serotonin levels. This would allow for remedial action should there be a major imbalance. We have a very well regarded neurotransmitter test avalable on our site.

Beyond neurotransmitters, neuroendocrine factors also influence the pathogenesis of PD. Dehydroepiandrosterone (DHEA), a steroid hormone produced primarily by the adrenal glands, exhibits neuroprotective properties and modulates the stress response. DHEA levels decline with age, and reduced DHEA secretion has been associated with neurodegenerative diseases, including PD. Preclinical studies suggest that DHEA supplementation may confer neuroprotection and mitigate motor deficits in PD animal models, highlighting its potential as a therapeutic target.

Stress is real

Cortisol, the primary glucocorticoid hormone released in response to stress, has been implicated in PD progression. Chronic stress and dysregulated cortisol secretion may exacerbate neuroinflammation, oxidative stress, and neuronal damage, accelerating the degenerative process in PD. Moreover, cortisol dysregulation can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, impairing circadian rhythms and exacerbating non-motor symptoms such as sleep disturbances and mood disorders in PD patients.

The intricate interplay between dopamine, GABA, serotonin, DHEA, and cortisol underscores the multifaceted nature of PD aetiology and pathophysiology. Dysfunction in one neurotransmitter or hormone can have ripple effects across multiple systems, contributing to the heterogeneous clinical presentation of PD. In additon, the interactions between these molecules further complicate our understanding of PD pathogenesis and treatment strategies.

From a naturopathic fucntionmal medicine perspective, targeting multiple neurotransmitter systems and neuroendocrine pathways may offer a more comprehensive approach to managing PD symptoms and slowing disease progression. Interventions aimed at enhancing dopaminergic function, restoring GABAergic balance, and modulating serotonergic activity remain the cornerstone of PD treatment. Additionally, strategies to optimize DHEA levels and mitigate cortisol dysregulation may hold promise as adjunctive therapies in PD management.

Our functional medicine specialist Max offers free 15 minute calls to discuss MacuDopa and holds a regular PD clinic for those interested in delving deeper into their condition. Book here.