Work

Pamheterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function

Year: 2014

Type: article

Abstract: Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation. Pam(+/-) mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam(+/-) phenotypes were recapitulated in Cu-restricted wild-type mice and rescued in Cu-supplemented Pam(+/-) mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam(+/-) mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild-type synaptic plasticity and sufficient to induce long-term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function.

Source: Annals of the New York Academy of Sciences

DOI: 10.1111/nyas.12378

Authors: Eric D. Gaier, Betty A. Eipper, Richard E. Mains

Institution: UConn Health

Language: English

Topic: Trace Elements in Health

Subfield: Nutrition and Dietetics

Field: Nursing

Domain: Health Sciences

Open Access status: green

Funder: National Institute of Diabetes and Digestive and Kidney Diseases

Award: Biochemistry and Physiology of Peptide Amidation