Legacy Research Institute

Danielle M. Osborne, Ph.D.

Assistant Scientist
R.S. Dow Neurobiology 
Legacy Research Institute

Phone: 503-413-2474  |  Email: dosborne@downeurobiology.org

CV (updated March 2024)
Peer Reviewed Publications
R.S. Dow Neurobiology Laboratories

Short Bio:

Dr. Osborne earned her Ph.D. in Behavioral Neuroscience from the University at Albany focusing on stress interactions with insulin signaling in the dorsal hippocampus with an additional emphasis on glucose metabolism in the hippocampus. She took a post-doctoral position at Legacy Research Institute to work on sex differences in neuropsychiatric disorders. She has since risen within LRI to become an Assistant Scientist, and with intramural support she has developed an independent line of research into using obesity models to better understand the sex differences and etiology of Alzheimer’s Disease.

Publication Highlights:

Sex differences in response to obesity and caloric restriction on cognition and hippocampal measures of autophagic-lysosomal transcripts and signaling pathways.
Baer SB, Dorn AD, Osborne DM. 
BMC Neurosci. 2024 Jan 2;25(1):1. PMCID: PMC10759648.
https://pubmed.ncbi.nlm.nih.gov/38166559/

Prolonged diet-induced obesity modifies DNA methylation and gene expression in the hippocampus.
Vander Velden JW, Osborne DM.
Neurosci Lett. 2022 May 29;780:136656.
https://pubmed.ncbi.nlm.nih.gov/35469824/

Obesity Prevents S-Adenosylmethionine-Mediated Improvements in Age-Related Peripheral and Hippocampal Outcomes.
Vander Velden JW, Osborne DM.
Nutrients. 2021 Apr 6;13(4):1201. PMCID: PMC8067411.
https://pubmed.ncbi.nlm.nih.gov/33917279/

Research Interests:

• Obesity-mediated susceptibility to Alzheimer’s Disease
• Autophagy and lysosomal degradation in Alzheimer's Disease
• Sex differences and neurosteroids
• Stress effects in the hippocampus

Research Focus:

The early events that culminate in Alzheimer’s Disease are poorly understood and difficult to study in a clinically relevant way. Although genetic models are an invaluable resource, 95% of Alzheimer’s cases have no clear genetic cause, making it difficult to identify early biomarkers and treatment inventions; often by the time cognitive deficits are apparent, the disease has progressed for over a decade, such that treatments cannot be effective with such severe atrophy of the brain.

Obesity and Type 2 Diabetes confer a 1.5-1.7 fold increase in risk for Alzheimer’s Disease, respectively. The brain undergoes substantial structural and functional changes with long-term consumption of an obesogenic diet. By studying these changes in susceptible brain regions, like the hippocampus, I hope to better understand the early molecular events that lead to Alzheimer’s Disease.

Previously, we examined changes in gene methylation stemming from long-term high-fat and high-sugar consumption. An obesogenic diet resulted in substantial promoter and intragenic methylation changes, and subsequent perturbations in mRNA expression of the Alzheimer’s risk gene BIN1, brain-derived neurotrophic factor, histone deacetylases, and other genes related to cognition. We are following up on these results to dive further into autophagy and mTOR related mechanisms that become dysfunctional in obesity.

Of paramount importance, is the full inclusion of males and females in my research. Prior to menopause, females enjoy enhanced neuroprotection from neurosteroids allopregnanolone and estrogen. With advanced age, the sex differences in neurodegeneration narrow; however, the pathways and mechanisms driving that effect can differ between the sexes. Additionally, inclusion of females in obesity and metabolic drivers of Alzheimer’s research is nearly non-existent. This must be remedied.

Current Projects:

1. Augmenting lysosomal function to counteract sex-specific changes in Alzheimer's disease models
2. Understanding early molecular changes in the brain due to menopause
3. Interactions between menopause and obesity on the brain