Analysis of differential gene expression supports a role for amyloid precursor protein and a protein kinase C substrate (MARCKS) in long‐term memory

Abstract

Previous work has identified the intermediate and medial part of the hyperstriatum ventrale (IMHV) as a region of the chick brain storing information acquired through the learning process of imprinting. We have examined in this brain region changes in expression of candidate genes involved in memory. Chicks were exposed to a rotating red box and the strength of their preference for it, a measure of learning, determined. Brain samples were removed approximately 24 h after training. Candidate genes whose expressions were different in IMHV samples derived from strongly imprinted chicks relative to those from chicks showing little or no learning were identified using subtractive hybridization. The translation products of two candidate genes were investigated further in samples from the left and right IMHV and from two other brain regions not previously implicated in imprinting, the left and right posterior neostriatum. One of the proteins was the amyloid precursor protein (APP), the other was myristoylated alanine rich C kinase substrate (MARCKS). In the left IMHV the levels of the two proteins increased with the strength of learning. The effects in the right IMHV were not significantly different from those in the left. There were no effects of learning in the posterior neostriatum. This is the first study to relate changes in the amounts of MARCKS and APP proteins to the strength of learning in a brain region known to be a memory store and demonstrates that the systematic identification of protein molecules involved in memory formation is possible.

The Chick as a Model for the Study of the Cellular Mechanisms and Potential Therapies for Alzheimer's Disease

“…The time-window of onset of amnesia relative to time of injection of ODNs and to time of training confirmed our previous finding that APP exerts its function during an early phase of memory formation and appears to be a necessary factor in the biochemical cascade involved in the transition between short- and long-term memory. Our findings on the importance of APP in learning were supported by reports [19] that APP gene expression in the young chick is related to the strength of memory retention for an imprinting task.…”

“…Furthermore, the chick embryo expresses the genes that encode the main proteases implicated in the production of APP, including BACE-1, BACE-2, presenilin-1, presenilin-2, and nicastrin as well as Neprilysin, the main A β -degrading enzyme, and ADAM-17, a protease implicated in the nonamyloidogenic processing of APP. Importantly, the level of the APP gene expression is related to the strength of learning in day-old chicks [19]. That makes the chick a useful natural model in which to study the cell biology and functions of APP and a potential “assay system” for drugs that regulate APP processing.…”

Proteomic analyses of limbic regions in neonatal male, female and androgen receptor knockout mice

“…MARCKS has been shown to be of importance for synaptic signaling [54] and plasticity [55] and is necessary for normal mouse brain development [52]. Previous studies have mainly focused on the role of this protein in processes related to memory [56, 57] and learning [53]. The present study is the first to report sex differences in brain protein levels of MARCKS and this result may provide knowledge regarding the molecular mechanisms involved in the well-established sex differences with respect to, for example, dendritic spines, dendrite length and the number of synapses [11].…”

GM1 ganglioside regulates the proteolysis of amyloid precursor protein

“…On the other hand, GM1 has been reported to have an inhibitory action on PKC and sAPPa is positively regulated by PKC activation. [40][41][42] GM1 may inhibit sAPPa secretion by inhibiting the PKC activity. Both hypotheses require and deserve further experimental work.…”