Sex Differences in Learning-Induced Protein Degradation in the Dorsal Hippocampus of Male and Female Mice
Mentor 1
Karyn Frick
Start Date
10-5-2022 10:00 AM
Description
Long-term memory formation has long been established as requiring de novo protein synthesis, meaning that protein synthesis is required for modifications to synapses. Protein degradation processes are equally important to memory; however, less research has been done on this topic. The main mechanism for degrading proteins within the cells is the ubiquitin proteasome system (UPS). In this pathway, substrate proteins are tagged with a polyubiquitin chain that is recognized by the 26S proteasome for degradation. Recent findings demonstrate that there are sex differences in the mechanisms that regulate UPS activity following fear learning across subcellular compartments of the neuron. However, the extent to which UPS activity differs between male and female mice in non-aversive forms of learning remain unclear. Here, we examined markers of UPS activity in the synaptic and cytoplasmic fractions of dorsal hippocampus (DH) tissue collected 1 hour following object training in adult male and female mice (n = 12/group/sex). Mice were first handled for 30 seconds per day for 3 days. They were then habituated in an empty testing arena for 5 minutes per day for 2 days. During training, mice accumulated 30 seconds of exploration with two identical objects and DH tissue was collected 1 hour after completion of training and fractionated to obtain synaptic and cytoplasmic fractions. We found that object training increased phosphorylation of the proteasomal subunit Rpt6 and PSD-95 in the DH synaptic fraction in male mice only. Conversely, female mice only had increased Rpt6 phosphorylation in the DH cytoplasmic fraction. The data suggest that there are sex-specific alterations in UPS activity across subcellular compartments. Finding sex differences contributes important information to the scientific field and should be studied more thoroughly for medical providers to be able to provide the best care possible.
Sex Differences in Learning-Induced Protein Degradation in the Dorsal Hippocampus of Male and Female Mice
Long-term memory formation has long been established as requiring de novo protein synthesis, meaning that protein synthesis is required for modifications to synapses. Protein degradation processes are equally important to memory; however, less research has been done on this topic. The main mechanism for degrading proteins within the cells is the ubiquitin proteasome system (UPS). In this pathway, substrate proteins are tagged with a polyubiquitin chain that is recognized by the 26S proteasome for degradation. Recent findings demonstrate that there are sex differences in the mechanisms that regulate UPS activity following fear learning across subcellular compartments of the neuron. However, the extent to which UPS activity differs between male and female mice in non-aversive forms of learning remain unclear. Here, we examined markers of UPS activity in the synaptic and cytoplasmic fractions of dorsal hippocampus (DH) tissue collected 1 hour following object training in adult male and female mice (n = 12/group/sex). Mice were first handled for 30 seconds per day for 3 days. They were then habituated in an empty testing arena for 5 minutes per day for 2 days. During training, mice accumulated 30 seconds of exploration with two identical objects and DH tissue was collected 1 hour after completion of training and fractionated to obtain synaptic and cytoplasmic fractions. We found that object training increased phosphorylation of the proteasomal subunit Rpt6 and PSD-95 in the DH synaptic fraction in male mice only. Conversely, female mice only had increased Rpt6 phosphorylation in the DH cytoplasmic fraction. The data suggest that there are sex-specific alterations in UPS activity across subcellular compartments. Finding sex differences contributes important information to the scientific field and should be studied more thoroughly for medical providers to be able to provide the best care possible.
