Publication
Possible Role of Dynorphins in Alzheimer's Disease and Age-Related Cognitive Deficits
Publisher:
S. Karger AG
Date:
22-08-2013
DOI:
10.1159/000353848
Abstract: b i Background/Aims: /i /b Expression of dynorphin, an endogenous opioid peptide, increases with age and has been associated with cognitive deficits in rodents. Elevated dynorphin levels have been reported in postmortem s les from Alzheimer's disease (AD) patients, and prodynorphin (PDYN) gene polymorphisms might be linked to cognitive function in the elderly. Activation of & #954 -opioid receptors by dynorphins has been associated with stress-related memory impairments. Interestingly, these peptides can also modulate glutamate neurotransmission and may affect synaptic plasticity underlying memory formation. N-methyl- smlcap D /smlcap -aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA) ionotropic glutamate receptor levels generally decrease with aging, and their function is impaired in AD. b i Methods: /i /b Here, we compared the impact of aging on ionotropic glutamate receptor levels in the hippoc al formation of wild-type (WT) and Pdyn knock-out (KO) mice. b i Results: /i /b We observed a significant reduction in GluR1 and GluR2 AMPA receptor subunits in the hippoc al formation of 18- to 25-month-old WT mice in comparison with 6-month-old mice. Conversely, the GluR1 protein level was maintained in old Pdyn KO mice, and the NMDA NR2B subunit level was increased by 42% when compared to old WT animals. b i Conclusions: /i /b These results suggest that elevated dynorphin expression occurring during aging and AD may mediate cognitive deficits by altering the glutamatergic system integrity.