Bovine Colostrum Extracellular Vesicles as Nutraceuticals or Pharmaceuticals for Parkinson’s Disease
Bovine Colostrum Extracellular Vesicles as Nutraceuticals or Pharmaceuticals for Parkinson’s Disease
ORCID ID
Graduation Date
Spring 5-9-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Interdisciplinary Graduate Program in Biomedical Sciences
First Advisor
Howard Gendelman, M.D.
Second Advisor
Natalia Osna, Ph.D
Third Advisor
Geoffrey Thiele, Ph.D.
Fourth Advisor
Sudipta Panja, Ph.D.
Abstract
Parkinson’s disease(PD), the second most common neurodegenerative disorder, is likely to become more prevalent as the average age of the population increases. Although there are several palliative therapies for PD, there are no clinically available disease-modifying treatments. It is reasonable to explore novel methods for targeting neuroinflammation and providing neuroprotection in PD. Here we sought to use colostrum milk extracellular vesicles(C-EVs) as a nutraceutical agent to downregulate neuroinflammation and ameliorate neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Activities of our EVs were validated in vitro with lipopolysaccharide(LPS) stimulated BV2 microglial and SH-S5Y neuronal cell lines. Several methods were used to evaluate the activities of the EVs. Ingenuity pathway analysis(IPA) of RNA from midbrain tissue collected during the MPTP study showed major differences in Z-scores for recruitment of leukocytes, recruitment of phagocytes, and the inflammatory activation pathways when mice were intoxicated with MPTP and in MPTP-intoxicated mice treated with C-EVs. Further transcriptomic analysis indicated that many genes that were upregulated by MPTP intoxication were downregulated when the mice were treated with C-EVs. This evidence was supported by qPCR. Microglial activation markers were also found to be significantly downregulated. Western blot analysis indicated that C-EV treatment in MPTP-intoxicated mice significantly decreased the expression of inflammasome proteins as well as associated caspases and cytokines. Histological analysis confirmed that microglial activation was downregulated. Additionally, we showed that treatment of C-EVs to BV2 cells could downregulate the expression of inflammatory markers, and this downregulation could be enhanced by enriching the EVs with anti-inflammatory miRNA cargo. Ultimately, we were able to show that C-EV treatment could downregulate neuroinflammation and thereby provide neuroprotection in models of PD.
Recommended Citation
Hollingsworth, Dawson E., "Bovine Colostrum Extracellular Vesicles as Nutraceuticals or Pharmaceuticals for Parkinson’s Disease" (2026). Theses & Dissertations. 1040.
https://digitalcommons.unmc.edu/etd/1040
Copy of Journal Article Which Contains Published Figures