Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

Abstract

Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and reactive oxygen species (ROS), were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory) was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR) was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time) also significantly decreased in the DHA-administered rats, thus suggesting that a higher coping capacity was present during fear stress in the DHA-administered rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95, and VAChT, and the antioxidative potentials in the hippocampus. These results suggest the usefulness of DHA for treating stress disorders.

Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation

“…In support of this, it has been previously reported that deficiencies in n-3 LCPUFA such as DHA in the brain, correlates with a reduction in the GluN2B amount leading to LTP impairment [93]. Moreover, the hippocampus of rats under treatment with DHA increases the expression of the NMDAR subunit GluN2B as well as in DHA-enriched cultured mouse hippocampal neurons [94,95].…”

The Protective Effect of Docosahexaenoic Acid on PC12 Cells in Oxidative Stress Induced by H2O2 through the TrkB-Erk1/2-CREB Pathway

“…Furthermore, DHA enhances spatial memory ability, stimulates neurogenesis, and protects the elderly from aging-related cognitive decline . In addition, a DHA treatment in rats resulted in changes in extinction memory and levels of brain cognition-related proteins . These findings demonstrate that there is a strong link between DHA and cognitive health.…”

“…15 In addition, a DHA treatment in rats resulted in changes in extinction memory and levels of brain cognition-related proteins. 16 These findings demonstrate that there is a strong link between DHA and cognitive health.…”

The gastrin-releasing peptide regulates stress-enhanced fear and dopamine signaling

“…Confirming our finding that the GRP removal prolongs fear extinction in the Grp -/- mice, the GRP decreases fear memory reconsolidation when applied intraperitoneally immediately following recall in rats (Murkar, Kent, Cayer, James, & Merali, 2018). Also, GRP protein levels and Grpr mRNA levels are increased following treatment with drug docosahexaenoic acid, which leads to facilitation of fear extinction (Hashimoto, Hossain, Katakura, Mamun, & Shido, 2018). These findings support earlier observations that a removal of the GRP signaling in vivo leads to enhanced and prolonged fear memory and deficient fear extinction in Grpr -/Y mice (Chaperon et al, 2012; Martel et al, 2012; Shumyatsky et al, 2002).…”