Expression of key synaptic proteins in Zebrafish (Danio Rerio) brain following caloric restriction and its mimetic and their relationship with gender

Abstract

Aging is a progressive decline of physiological functioning and metabolic processes. Among all the organs, the brain seems to be the most vulnerable part of the body to the age-related changes because of the relatively high consumption of oxygen and glucose as compared to other organs. Both structural and cognitive changes occur during the aging process. A great effort has been spent to ameliorate the outcomes occurring within the brain as a result of aging. Caloric restriction (CR) is considered to be the only non-genetic intervention which decreases age-related cognitive decline. Rapamycin (RAP) has become a candidate drug which was shown to mimic the effects of CR by blocking the nutrient-sensing pathway, the mammalian target of Rapamycin, (mTOR) pathway. The first aim of this study was to investigate the expressions of key synaptic proteins; gephyrin, PSD-95 and synaptophysin, which are involved in the synaptic plasticity, after short-term (4 weeks) CR and RAP interventions in young and old, male and female zebrafish. The second aim was to investigate whether the expression of glutamate receptor subunits, NR2B and GluR2/3, display a sexually dimorphic pattern in middle age zebrafish. It was found that there was no significant difference in the expression of key synaptic proteins between the CR and RAP animal groups as compared to the ad libitium (AL) fed group and also no significance was found in the expression of NR2B and GluR2/3 in middle-aged male and female zebrafish. Highlighted studies in this thesis demonstrate that short-term (4 weeks) of CR and RAP treatments were too short to observe an effect in the expression level of gephyrin, synaptophysin, and PSD-95, and in the middle age, expression of NR2B and GluR2/3 did not display sexually dimorphic pattern. Our initial results of key synaptic protein levels indicate that they are stable throughout aging with respect to gender and CR interventions.