An overview of the neuroendocrine system in Parkinson’s disease: what is the impact on diagnosis and treatment?

ABSTRACT

Introduction: A growing body of evidence indicates that neuroendocrine interactions may occur at all levels of the brain-gut-microbiota axis, which is directly involved in the pathogenesis of Parkinson’s disease (PD).

Areas covered: The review presents some current and emerging concepts regarding the organization and functioning of the neuroendocrine system as well as the role of neuroendocrine disturbances in the pathophysiology and symptomatology of PD. The concept of the brain-gut-microbiota triad interactions in the neuroendocrine system and PD is proposed. In PD, dysregulation of the main neuroendocrine axes coordinated by the hypothalamus is accompanied by disruptions at the peripheral level, which involve enteroendocrine cells producing numerous neuropeptides. Moreover, the important role of the gut microbiota as a main coordinator of immune and neuroendocrine interactions is discussed. The potential diagnostic and therapeutic implications in the context of the recent developments in the fields of neuroendocrinology and neurodegeneration are also presented.

Expert opinion: Unraveling complex neuroendocrine interactions in the course of PD may provide crucial diagnostic implications and novel therapeutic approaches including the application of gut neuropeptides and gut microbiota modification.

KEYWORDS:

• Parkinson’s disease
• neuroendocrine system
• brain-gut axis
• enteroendocrine cells
• gut microbiota

Article highlights

• Recently, a more holistic concept of the neuroendocrine system is emerging, which encompasses not only the centrally regulated axes controlled by the hypothalamus, but also diffuse neuroendocrine cells, and a direct input from the microbial community as an integral part of the system.

• Accumulating epidemiological, clinical, and experimental data indicate that Parkinson’s disease (PD) may begin in the gut involving α-synucleinopathy of the enteric nervous system closely interacting with enteroendocrine cells.

• Whereas the classic motor symptoms of PD are associated with the nigrostriatal system degeneration, the vast spectrum of non-motor symptoms is attributed to much more complex etiology including neuroendocrine disturbances.

• A dysregulation of the hypothalamic-pituitary-adrenal axis reflected by alterations in adrenocorticotropic hormone (ACTH) and cortisol levels has been suggested to be involved in exacerbation or progression of PD. Disturbances in the core element of the neuroendocrine system including the hypothalamus are associated with circadian rhythm disruption and altered regulation of stress and immune responses.

• Screening for hypothyroidism should be considered in PD patients, since concomitant thyroid dysfunction may mimic the symptoms of PD, aggravate its severity or cause resistance to levodopa. To avoid false-negative results due to acute reduction in TSH level induced by dopaminergic drugs, the blood sample for TSH in PD patients should be collected before the first levodopa dose in the morning.

• Current data confirm significant sex differences in the epidemiology, clinical manifestation, molecular pathology and treatment outcomes in PD. Female patients present PD onset at a later age, tremor-predominant PD, decreased capacity for daily activities, higher non-motor symptom score and sever levodopa-induced dyskinesia. Male PD patients compared to female ones need higher doses of levodopa for optimal symptom control. The potential disease-modifying effect of hormonal replacement therapy is discussed.

• Enteroendocrine cells (EECs) combining the features of endocrine and neural cells represent an important element of neuroendocrine interactions and support the role of the brain-gut axis disturbances in PD. Based on neuroprotective effects of numerous brain-gut peptides produced by EECs related to their anti-inflammatory, anti-oxidant, anti-apoptotic and neurotrophic actions they may represent promising therapeutic targets in PD.

• A growing body of evidence confirms the role of gut dysbiosis in the pathogenesis and symptomatology of PD. A direct impact of the gut microbiota on the brain-gut axis involves immunological, neural, and neuroendocrine mechanisms. The concept of microbial endocrinology supports the emerging evidence on a close bidirectional interaction between the neuroendocrine system and the gut microbiota.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author received no specific funding for this work.