Research suggests that localised oxidative stress may contribute to dopaminergic neuron damage and death. However in 2005 Dianne McFarlane found that "there was no evidence of systemic accumulation of oxidative stress markers or deficiencies in antioxidant capacity in horses with PPID, suggesting that these are unlikely to be major predisposing factors in the development of PPID" (Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses).
In her 2011 paper on Equine PPID, Dr McFarlane states that pituitary antioxidant capacity has not been shown to be impaired in horses with PPID, but that the impairment of the activity of pituitary manganese superoxide dismutase found in older horses may contribute to the risk of PPID developing with age.
She goes on to say that excellent nutrition is important for horses with PPID, and that in theory, feeds high in antioxidants could slow the neurodegenerative process associated with PPID, but that there is currently no evidence for this. Early treatment with pergolide to replace the missing dopamine and reduce excess hormone production and the clinical signs of PPID is advised. Interestingly, research by Gille et al. (2002) found that "pergolide protects dopaminergic neurons under conditions of elevated oxidative stress"; similarly research by Uberti et al. in the same year suggested that "pergolide ... may interfere with the early phases of the oxidative stress-induced neurotoxic process". Dr McFarlane theorises that any antioxidant and neuroprotective properties of pergolide could be beneficial in slowing the progression of PPID.
In her presentation Is it PPID or is it EMS – Diagnosing Equine Endocrine Disease, Dianne McFarlane suggests that horses with EMS may be at greater risk of developing PPID as they get older – horses with EMS should be monitored and tested for PPID.
In conclusion, optimal management and treatment with pergolide is recommended for horses with PPID, but it appears that further research is needed before we can say for sure exactly what might cause or slow the progression of this common equine neurodegenerative disease.
Possible causes of PPID are discussed at the 2011 Equine Endocrinology Summit:
Pathophysiology of Pituitary Pars Intermedia Dysfunction in 2011 Dianne McFarlane, DVM, PhD, Dipl. ACVIM
See also Vet Clin North Am Equine Pract. 2011 Apr;27(1):93-113 (part of paper available online)
Equine pituitary pars intermedia dysfunction
Fortin JS, Hetak AA, Duggan KE, Burglass CM, Penticoff HB, Schott II HC
Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
Scientific Reports August 2021 11, 16036. https://doi.org/10.1038/s41598-021-95396-7. Open Access.
Parkinson's Disease & PPID/Causes of PPID