Two Behavioral Tests Allow a Better Correlation Between Cognitive Function and Expression of Synaptic Proteins

Abstract

The molecular substrate of age-associated cognitive decline (AACD) is still elusive. Evidence indicates that AACD is related to synaptic impairment in hippocampus, but different hippocampal regions play different roles, with the dorsal hippocampus (DH) associated to spatial learning, and the ventral hippocampus (VH) crucial for emotionality. If changes in hippocampal function contributes to AACD, this contribution may be reflected in alterations of synaptic protein levels. A commonly used approach to investigate this issue is western blotting. When this technique is applied to the entire hippocampus and the cognitive impairment is evaluated by a single task, changes in expression of a protein might undergo a “dilution effect”, as they may occur only in a given hippocampal region. We show that two behavioral tests yield more accurate results than one test in evaluating the function of the whole rat hippocampus by studying the expression of synaptotagmin 1 (SYT1), a vesicular protein whose expression in aged hippocampus is reportedly inconsistent. Analysis of SYT1 levels in the whole hippocampus of rats selected by the Morris water maze (MWM) test only failed to highlight a difference, whereas analysis of SYT1 levels in the whole hippocampus of rats categorized by both the MWM and the step-through passive avoidance (STPA) tests demonstrated a significant increase of SYT1 level in impaired rats. These findings, besides showing that SYT1 increases in impaired aged rats, suggest that using the whole hippocampus in blotting studies may prevent false negative results only if animals are categorized with tests exploring both DH and VH.

Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus

“…As an example, aging decreases the energy status of cells [ 4 ] and disrupts lipid homeostasis, namely cholesterol metabolism [ 5 ]. Other alterations in the brain include increased oxidative stress [ 6 ] and inflammation [ 7 ], synaptic impairment [ 8 ], and decreased brain trophism [ 9 ].…”

Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder

“…Synaptotagmin I (SYT1) is a synaptic vesicle protein that functions as a calcium sensor and is a main regulator of the SNARE complex. Convincing preclinical data have shown that SYT1 expression correlates with cognitive measures and neuronal function in rodents (Balietti et al 2018;Jia et al 2010;Chen et al 2013;Zhang et al 2017;Yu et al 2018). Recently, human genome-wide association studies (GWAS) have identified associated SNPs on SYT1 gene with personality traits as neuroticism (Luciano et al 2018), and with educational attainment and cognitive performance (Lee et al 2018).…”