Levels of brain-derived neurotrophic factor (BDNF) — a protein important in promoting the survival of dopaminergic neurons — are abnormally low in patients with Parkinson’s disease, regardless of whether these patients also have depression, a common non-motor symptom associated with the disease, a systematic review study reveals.

The study also revealed that exercise can increase BDNF levels in Parkinson’s patients, highlighting exercise’s potential not only to treat depression, but also motor symptoms typically associated with Parkinson’s disease.

The systematic review, “ Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: A systematic review and meta-analysis ,” was published in Brain Research.

BDNF is an abundant protein whose main function is to protect dopaminergic neurons located in the substantia nigra — a region of the brain responsible for movement control — that are gradually lost in the course of Parkinson’s disease.

Although no literature consensus exists, some studies have shown that blood serum BDNF levels decrease in patients with depression and increase after intense exercise in healthy adults.

In this systematic review, the authors focused on gathering and discussing data from previous studies assessing blood serum levels of BDNF in Parkinson’s patients.

After a thorough screening in three different databases (MEDLINE, EMBASE and SCOPUS), 12 eligible studies were selected, including five comparing serum BDNF levels of Parkinson’s patients to those of healthy control subjects and three comparing serum BDNF levels of depressed and non-depressed Parkinson’s patients.

Data revealed that Parkinson’s patients tend to have lower levels of BDNF in their serum, compared to healthy control individuals (mean difference of 2.99 ng/mL). Parkinson’s patients who also had depression had even lower levels of BDNF compared to healthy control subjects (mean difference of 4.83 ng/mL).

No differences in BDNF levels were found between depressed and non-depressed Parkinson’s patients.

There was also a positive correlation between serum BDNF levels and patients’ male gender, disease duration and Hoehn and Yahr motor score — a commonly used system to describe the progression of Parkinson’s symptoms.

There is “a direct relationship between [Parkinson’s disease] progression and worsening of motor symptoms and higher serum BDNF. We believe that this could be a result of a compensatory mechanism in response to progressive loss of dopaminergic neurons of the substantia nigra and progressive [reduction] of neurotrophin expression in the remaining neurons. This could also reflect a possible effect of medications, namely antidepressants and dopamine replacement therapy,” researchers said.

Four studies also analyzed the effects of exercise on serum BDNF levels, while two others focused on the relationship between Parkinson’s disease severity and patients’ physical capacity and serum BDNF levels.

While there was no relationship between patients’ physical capacity and serum BDNF levels, a significant increase in BDNF levels was seen in patients with mild to moderate Parkinson’s after four or eight weeks of physical training, which was accompanied by an improvement of UPDRS motor scores and patients’ performance on the 6-minute walking test, used to assess aerobic capacity and endurance.

Another study reported similar findings in depressed Parkinson’s patients who participated in a 12-week exercise program.

“Our results proved that PD is of equal potential to [decrease] BDNF expression as depression, which is a common co-morbid condition in PD. The potential for exercise to induce BDNF expression in PD patients justifies that physical training might prove useful to treat depressive symptoms as well as motor complications of PD patients,” researchers concluded.