Doctoral defence: Kelli Somelar-Duracz „The molecular and cellular mechanisms of brain plasticity impairing factors”

On August 27th 2024 Kelli Somelar-Duracz will defend her thesis „The molecular and cellular mechanisms of brain plasticity impairing factors”.  

Supervisors: 
Associate professor Külli Jaako, University of Tartu
Professor Anti Kalda, University of Tartu

Opponent: 
Professor Markus Forsberg, University of Eastern Finland (Kuopio, Finland).

Summary
The brain is plastic, i.e., able to adapt and change its structure and functions during development, learning, memory formation, and recovery following injury. Adult hippocampal neurogenesis is a unique form of brain plasticity that contributes to memory encoding and mood regulation, and its dysfunctions are associated with depression and memory impairments. Impairments in brain plasticity also take place in the brain's dopaminergic reward region during addiction. Animal studies have suggested that alterations in gene expression, which underlie addiction, may be mediated by epigenetic DNA editors, DNA methyltransferases, and demethylases (DNMT and TET enzymes).

The current thesis aims to elucidate the cellular and molecular mechanisms of brain plasticity-impairing factors, such as chronic neuropathic pain, vitamin D deficiency (VDD), chronic stress, and psychostimulant exposure. Chronic neuropathic pain induced anxiety and depressive-like behavior, as well as memory impairments in mice, and these impairments were accompanied by reduced neurogenesis and increased microglial reactivity. Long-term VDD induced impairments in short- and long-term memory, relearning abilities, and self-care behaviors in mice co-occurred with decreased neurogenesis and signs of neuroinflammation. However, VDD did not further worsen the adverse effects of chronic stress. We also evaluated how psychostimulants affect DNMT and TET enzymes in human peripheral blood mononuclear cells. We found that repeated treatments with psychostimulants decreased the activity of TET enzymes and altered inflammatory cytokine profiles. Co-treatments with cocaine and a DNMT inhibitor reduced the effect of cocaine on the activity of TET enzymes. However, the therapeutic potential of DNMT inhibition needs further investigation. 

The results of the current study help to understand how different pathologies and environmental factors affect neurogenesis, glial reactivity, and epigenetic DNA modifiers. The observed reduction in neurogenesis and signs of neuroinflammation may contribute to behavioral alterations. The gained insights about fundamental brain plasticity mechanisms may contribute to developing future prevention and treatment strategies.

You can also watch defense via Teams.