Fellowship for Xuan Nguyen: Dynorphin in Age-Related Impairment of Learning/Memory

The research during this period continued as planned, with further neurobiological and biochemical characterization of the prodynorphin (Pdyn) knockout (-/-) mice along with other studies to test the potential role of prodynorphin-derived peptides in CNS changes associated with aging. The hypothesis of a detrimental effect of long-term dynorphin exposure in the brain with aging has been supported by literature reports of increased dynorphin levels not only after CNS trauma or excitotoxic insult but also with normal aging in rats, especially if concomitant cognitive deficits are present. To evaluate this premise in the particular mouse strain used in our behavioral experiments, radioimmunoassay for the dynorphin A peptide was performed in various regions of the wild-type (WT) 129SvEv mouse brain and showed that dynorphin A increases with aging in frontal cortex and striatum, but not hippocampus (Figure 1).