Hippocampal infusions of MARCKS peptides impair memory of rats on the radial-arm maze.
In vitro hippocampal studies by Gay et al. (2008) demonstrated that a myristoylated alanine-rich C kinase substrate (MARCKS) peptide comprising the phosphorylation site or effector domain of the protein acts as a powerful inhibitor of alpha7 nicotinic acetylcholine receptors (nAChRs), which are known to be critically involved in memory function. However, behavioral consequences of hippocampal MARCKS peptide infusions have not been investigated. The purpose of the current study was to determine if local infusions in the rat ventral hippocampus of long (comprising amino acids 151-175) and short (amino acids 159-165) forms of MARCKS peptides could affect memory performance in the 16-arm radial maze. Our results demonstrated a dramatic impairment of both working (changing) and reference (constant) memory with MARCKS(151-175) only. The shorter MARCKS peptide did not affect memory performance. This is in line with in vitro results reported by Gay et al. (2008) that long, but not short, MARCKS peptides inhibit alpha7 nAChRs. We also found that the effect of the MARCKS(151-175) peptide was dose-dependent, with a robust memory impairment at 10 microg/side, and smaller inconsistent effects at lower doses. Our present behavioral study, together with the earlier in vitro study by Gay et al. (2008), suggests that effector domain MARCKS peptides could play a significant role in memory regulation and impairment.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Olga A
OA
Timofeeva
Donnie
D
Eddins
Jerrel L
JL
Yakel
Perry J
PJ
Blackshear
Edward D
ED
Levin
D000704:Analysis of Variance; D000818:Animals; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D018782:Maze Learning / Q000187:drug effects*; D008565:Membrane Proteins / Q000008:administration & dosage*; D008570:Memory, Short-Term / Q000502:physiology*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects*
D047908:Intracellular Signaling Peptides and Proteins; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D010446:Peptide Fragments; D000076250:Myristoylated Alanine-Rich C Kinase Substrate