Mitochondrial Dynamics Imbalance as a Potential Driver of Neuronal Decline in the Aging Nervous System of Lymnaea stagnalis

Aging is associated with a progressive decline in multiple physiological functions, including impairments in neuronal function and cognitive abilities such as learning and memory. As global populations age, elucidating the biological mechanisms underlying brain aging and cognitive decline has become increasingly important. Mitochondrial dysfunction has long been implicated in the aging process, as neurons rely heavily on mitochondrial metabolism to meet their high energetic demands. However, the specific mechanisms through which mitochondrial dysfunction contributes to neuronal and behavioral decline during normal brain aging remain incompletely understood. This thesis investigates how age-related alterations in mitochondrial respiration, mitochondrial fission–fusion balance, and metabolic regulation contribute to functional decline in the central nervous system. Using the pond snail Lymnaea stagnalis as an invertebrate model of neuronal aging, the general hypothesis that disruption of mitochondrial fission–fusion balance contributes to neuronal dysfunction during aging was examined. The findings demonstrate that normal brain aging in L. stagnalis is associated with reduced cellular respiration, impaired metabolic redox balance, and decreased mitochondrial density and network complexity. Pharmacological manipulation of mitochondrial fission-fusion balance revealed that fission-fusion imbalance disrupts mitochondrial homeostasis and alters mitochondrial membrane potential in an age-dependent manner. Promotion of mi-tochondrial fusion increased mitochondrial elongation and connectivity in both young and aged CNS tissue; however, these structural changes did not produce proportional increases in oxygen consumption or restore mitochondrial reserve capacity in aged neurons. This suggests that increased mitochondrial connectivity and network complexity may not necessarily enhance mitochondrial respiratory efficiency during aging. Furthermore, neuronal respiration in intact CNS exhibited complex non-linear kinetics, indicating that oxygen consumption may involve physiological mechanisms beyond classical oxidative phosphorylation alone. These findings highlight the importance of balanced mitochondrial fission–fusion dynamics for maintaining mitochondrial homeostasis and provide new insight into the relationship among mitochondrial organization, cellular metabolism, and neuronal aging.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Discipline thesis:degree_discipline

Biological Sciences

Grantor

Science

Year dc:date.issued

2026

Author dc:creator

• Ehtemam, Farzaneh

Advisor dc:contributor.advisor

• Wildering, Willem Carel

Committee members dc:contributor.committeemember

• Lebenzon, Jacqueline Erica
• Theodor, Jessica Madeleine

• aging
• neuron
• mitochondria
• respiration
• fission
• fusion
• oxidative stress
• fatty acid
• excitability
• memory
• L. stagnalis

Statement dc:rights

• Unless otherwise indicated, this material is protected by copyright and has been made available with authorization from the copyright owner. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

en

DOI

https://dx.doi.org/10.11575/PRISM/51667

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/125387