Levels of glial cell line-derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson's disease.

Abstract

Growth factors can facilitate hippocampus-based learning and memory and are potential targets for treatment of cognitive dysfunction via their neuroprotective and neurorestorative effects. Dementia is common in Parkinson's disease (PD), but treatment options are limited. We aimed to determine if levels of growth factors are altered in the hippocampus of patients with PD, and if such alterations are associated with PD pathology. Enzyme-linked immunosorbent assays were used to quantify seven growth factors in fresh frozen hippocampus from 10 PD and nine age-matched control brains. Western blotting and immunohistochemistry were used to explore cellular and inflammatory changes that may be associated with growth factor alterations. In the PD hippocampus, protein levels of glial cell line-derived neurotrophic factor were significantly decreased, despite no evidence of neuronal loss. In contrast, protein levels of fibroblast growth factor 2 and cerebral dopamine neurotrophic factor were significantly increased in PD compared to controls. Levels of the growth factors epidermal growth factor, heparin-binding epidermal growth factor, brain-derived neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor did not differ between groups. Our data demonstrate changes in specific growth factors in the hippocampus of the PD brain, which potentially represent targets for modification to help attenuate cognitive decline in PD. These data also suggest that multiple growth factors and direction of change needs to be considered when approaching growth factors as a potential treatment for cognitive decline.

• Authors: Sophie Virachit, Kathryn J Mathews, Veronica Cottam, Eryn Werry, Emilia Galli, Elisabeth Rappou, Pӓivi Lindholm, Mart Saarma, Glenda M Halliday, Cynthia Shannon Weickert, Kay L Double
• Journal: Brain pathology (Zurich, Switzerland) (Brain Pathol) Vol. 29 Issue 6 Pg. 813-825 (11 2019) ISSN: 1750-3639 [Electronic] Switzerland
• PMID: 31033033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 International Society of Neuropathology.

Chemical References

• Brain-Derived Neurotrophic Factor
• CDNF protein, human
• Glial Cell Line-Derived Neurotrophic Factors
• Intercellular Signaling Peptides and Proteins
• MANF protein, human
• Nerve Growth Factors
• Fibroblast Growth Factor 2
• Dopamine

Topics

• Aged
• Aged, 80 and over
• Brain (pathology)
• Brain-Derived Neurotrophic Factor (metabolism)
• Corpus Striatum (pathology)
• Dopamine (metabolism)
• Female
• Fibroblast Growth Factor 2 (metabolism)
• Glial Cell Line-Derived Neurotrophic Factors (metabolism)
• Hippocampus (metabolism, pathology)
• Humans
• Intercellular Signaling Peptides and Proteins (analysis, metabolism)
• Male
• Nerve Growth Factors (metabolism)
• Neuroglia (metabolism)
• Parkinson Disease (metabolism)
• Substantia Nigra (pathology)