̽��ϵ��

Topic

Role of pathologically elevated TNF-α in regulating dendritic spine and synaptic stability in vitro

School of Medical Sciences

Date & location

• Thursday, April 16, 2026
• 9:00 A.M.
• Medical Sciences Building, Room 150

Examining Committee

Supervisory Committee

• Dr. Leigh Anne Swayne, School of Medical Sciences, ̽��ϵ�� (Supervisor)
• Dr. Craig Brown, School of Medical Sciences, UVic (Member)
• Dr. Caroline Cameron, Department of Biochemistry and Microbiology, UVic (Outside Member)

External Examiner

• Dr. Nicole Templeman, Department of Biology, UVic

Chair of Oral Examination

• Dr. Mohammadhossein Karimi, Department of Mechanical Engineering, UVic

Abstract

Dendritic spine and synaptic dysfunction are hallmarks of neurodegenerative and neurodevelopmental disorders associated with chronic neuroinflammation. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) is a key driver of this inflammatory response and contributes to disease progression. Previous studies have shown that elevated TNF-α levels associated with inflammatory conditions could impair spine structure and synaptic function. However, no study has investigated the impact of pathologically elevated TNF-α on dendritic spine and synaptic stability in vitro. Using primary mouse cortical cultures, we demonstrated that elevated TNF-α levels reduced dendritic spine and synapse size and intensity without affecting density, suggesting it may further impair synaptic maturation and function. Notably, treatment with the TNF-α inhibitor etanercept (ETN) failed to rescue these changes despite effectively inhibiting TNF-α-induced NF-κB activation. Our findings suggest that ETN may inhibit tmTNF-mediated neuroprotective effects, while residual unbound sTNF-α continues to drive proinflammatory signaling through TNFR1. Together, these findings highlight TNF-α’s pivotal role in regulating synaptic stability and underscore the need for therapies that block its neuroinflammatory effects without compromising neuroprotective signaling.