Keywords
Diphenhydramine; Neuroscience; Cellular Biology; Development; Neuro-2a; Drug Exposure
Abstract
Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, or 100 ng/mL of diphenhydramine. Immunofluorescence staining was utilized to assess morphological alteration via projection length and cell diameter. MTS assays determined cellular metabolic activity/proliferation. For protein expression, western blotting was used to quantify Tau-5, Vesicle Acetylcholine Transporter, and amyloid-beta protein levels. Acetylcholine assays were utilized to determine acetylcholine activity across these same treatment groups. Results from this study suggest that diphenhydramine impairs projection growth and differentiation at both 50 ng/mL and 100 ng/mL, with distinct disruption at 50 ng/mL. These results provide key insights into the dose-dependent mechanism underlying anticholinergic neurotoxicity, with implications for drug safety and therapeutic development. Future research will explore pathways involved in diphenhydramine induced neurotoxicity by utilizing RT-qPCR and investigate its effect in vivo.
Thesis Completion Year
2026
Thesis Completion Semester
Spring
Thesis Chair
Borgon, Robert
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Thesis Discipline
Molecular Neurobiology
Language
English
Access Status
Open Access
Length of Campus Access
None
Campus Location
Orlando (Main) Campus
STARS Citation
McIntyre, Jordan B., "Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact on Neuro-2a Cell Morphology, Expression, and Viability" (2026). Honors Undergraduate Theses. 635.
https://stars.library.ucf.edu/hut2024/635
Included in
Cell Biology Commons, Chemical Actions and Uses Commons, Developmental Biology Commons, Developmental Neuroscience Commons, Macromolecular Substances Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Medical Neurobiology Commons, Medical Toxicology Commons, Molecular and Cellular Neuroscience Commons, Molecular Biology Commons, Neurosciences Commons, Other Chemicals and Drugs Commons
Accessibility Statement
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