The Dopamine System: Insights between Kidney and Brain

Abstract

BACKGROUND: Chronic kidney disease (CKD) is one of the most common diseases in adult age and it is typical of older adults. Recent data suggest that almost half of the elders have CKD. It is now clear that CKD is accompanied, in the early stages, by cognitive impairment, together with depression and subtle abnormalities in motor control (such as gait and balance alterations). SUMMARY: Several data suggest a link between brain dopamine and kidney diseases. Metabolic syndrome and diabetes can affect dopamine neuron survival (leading to Parkinson’s Disease). Several uremic toxins in CKD (uric acid, indoxyl sulphate) and trace elements accumulating in CKD (aluminium, manganese) can also modify the dopaminergic system. Hormones produced by the kidney such as vitamin D are neuroprotective for dopamine neurons. Dopaminergic drugs are useful for the treatment of a common sleep disorder in CKD, the restless legs syndrome. However, experiments on animal models of CKD show conflicting results regarding a modification of dopamine neurons. KEY MESSAGES: Several observations suggest a limited relevance of the dopaminergic system in CKD-related cognitive impairment. However, a common sleep disturbance in CKD, the restless leg syndrome, improves with dopaminergic drugs. Therefore, it remains to be established the role of the dopamine system in subtle motor dysfunction observed in CKD, such as tremors, gait alterations, and central sleep apnea.

Inferring Multi-Organ Genetic Causal Connections using Imaging and Clinical Data through Mendelian Randomization

“…Brain disorders were the most prevalent among the significant relationships identified (23/62, mental and behavioral disorders (14) and diseases of the nervous system (9)), followed by endocrine, nutritional and metabolic diseases (18/62) ( Table S5 ). These findings aligned with ongoing research on the complex interplay between the brain and abdominal organs, such as the brain-gut connection 56–58 , brain-kidney connection 59,60 , and brain-liver connection 61 . Specifically, Alzheimer’s disease and dementia were linked to a reduction in liver volume and percent of liver fat (| β |>0.02, P < 1.28ξ10 −4 , 6/8 MR methods significant).…”

“…These findings corroborated ongoing research concerning the interplay between the brain and abdominal organs, such as the brain-gut connection [62][63][64] , brain-kidney connection 65,66 , and brain-liver connection 67 .…”

Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies

“…DA is a neuromodulator that has the ability to diffuse away from the site of its release, activating receptors that are far from the terminal; this ability is called transmission volume [ 2 ]. In this sense, DA receptors have been identified in nonneuronal tissues, which has been related to their therapeutic potential in pathologies such as sepsis or septic shock, blood pressure, renal failure, diabetes, and obesity, among others [ 6 , 7 , 8 ]. In addition, it has been reported that DA and dopaminergic drugs such as bromocriptine, cabergoline, pramipexole, and ropinirole have shown anti-inflammatory and antioxidant functions in different kinds of cells, reducing reactive oxygen species (ROS) accumulation, preserving glutathione (GSH) and other antioxidant enzymes, and decreasing lipid peroxidation [ 9 , 10 , 11 , 12 , 13 , 14 ].…”

Association of metabolic syndrome and its components with Parkinson’s disease: a cross-sectional study

“…When insulin function in the brain is compromised, it initiates cellular disturbances, resulting in pathological states. For example, MetS and DM can render dopaminergic neurons vulnerable [ 40 ] and affect dopamine neuron survival [ 41 ]. IR may lead to reduced expression of dopamine transporter proteins on the striatal surface, as demonstrated in animal models [ 42 ].…”