Research Protocol: Investigating the Effect of Prenatal Nicotine Exposure on Short-term and Long-term Memory Using Behavioural and Molecular Models

Abstract

Introduction: Prenatal nicotine exposure disrupts brain development, leading to conditions like ADHD, anxiety, and cognitive deficits by altering neurotransmitter activity and gene expression. Nicotine affects brain regions such as the prefrontal cortex, hippocampus, and amygdala, reducing brain volume, particularly in the frontal cortex and cerebellum. While research links prenatal nicotine to memory deficits, gaps remain in understanding its effects on molecular mechanisms like proteasomal activity, protein synthesis, and Late-Phase Long-Term Potentiation (L-LTP). This study combines behavioral tasks with proteasomal activity analysis to investigate these mechanisms.

Methods: This study design uses behavioural tests, Active Place Avoidance (APA) and Novel Object Recognition (NOR) and protein synthesis assessment to investigate the molecular and behavioral effects of prenatal nicotine exposure on short and long-term memory.

Anticipated Results: APA task: The number of entries into the shock zone, the duration spent in the shock zone, and the latency to enter the shock zone will be significantly different between experimental and control groups (p< 0.05). NOR test: The time spent exploring the novel object will be significantly different between experimental and control groups (p< 0.05). Protein synthesis evaluation: The t-test that evaluates proteasome activity will yield significant differences between experimental and control groups (p< 0.05). We hypothesize that mice prenatally exposed to nicotine (experimental group) will exhibit significant difference in proteasomal activity during L-LTP, alongside measurable difference seen in APA and NOR test performance, compared to the control group.

Discussion: Anticipated results suggest prenatal nicotine exposure affects protein synthesis and proteasome activity, key to L-LTP and memory. Challenges include ethical and logistical issues with animal use, nicotine variability, and maintaining experimental precision in APA and NOR tests. Measuring L-LTP and neuronal protein synthesis is complex, requiring advanced methods and standardized protocols to address region-specific processes and variability.

Conclusion: This study explores prenatal nicotine exposure's impact on memory through altered proteasome activity and behavioral tests (APA, NOR). By analyzing protein synthesis in L-LTP, it examines disruptions in synaptic plasticity. Future research could use fMRI to study protein synthesis in prenatally exposed individuals.