sgk , a primary glucocorticoid-induced gene, facilitates memory consolidation of spatial learning in rats

Abstract

By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are expressed differentially between the fast learners and slow learners in the water maze learning task. One of these cDNA fragments encodes the rat serum-and glucocorticoid-inducible kinase (sgk) gene. Northern blot analysis revealed that the sgk mRNA level was approximately 4-fold higher in the hippocampus of fast learners than slow learners. In situ hybridization results indicated that sgk mRNA level was increased markedly in CA1, CA3, and dentate gyrus of hippocampus in fast learners. Transient transfection of the sgk mutant DNA to the CA1 area impaired, whereas transfection of the sgk wild-type DNA facilitated water maze performance in rats. These results provide direct evidence that enhanced sgk expression facilitates memory consolidation of spatial learning in rats. These results also elucidate the molecular mechanism of glucocorticoidinduced memory facilitation in mammals. It is well accepted that long-term memory formation requires de novo RNA and protein synthesis. Evidence supporting this notion comes from the results that inhibition of mRNA and protein synthesis impairs long-term memory formation in various behavioral tasks in rats (1-3). This evidence suggests that neural activities associated with learning leads to the expression of various genes, and the protein products of these genes play important roles in the process of memory formation. Extensive efforts have been made to identify genes that are associated specifically with certain forms of learning and memory. For example, by using two-dimensional gel analysis, several candidate proteins have been identified that are related to long-term sensitization of the gill-withdrawal reflex in Aplysia (4). Screening in Drosophila mutants has yielded approximately 10 genes that are associated with the process of olfactory learning and memory (5). Further, by using a double-labeling method, proteins that show increased glycosylation as a result of training were identified in rats (6). The methods used in the above studies are effective; however, identifying and characterizing these genes takes a long time when using these methods. In addition, most of these studies were carried out in the invertebrate, in which the neuronal circuits and genes involved in memory formation probably are different from that in the vertebrate.In a more recent study, by using differential display-PCR (DD-PCR), we have successfully identified genes that are associated specifically with memory formation of one-way inhibitory avoidance learning in rats (7,8). Some of these results were confirmed further by a gene-knockout study (9). These results suggest that DD-PCR is an effective method in identifying genes that are involved in complex forms of learning and memory in the vertebrate. Therefore, we have adopted the same strategy in the present study to identify genes that are associated specifically with memory formation of spatial learning in rats. The Morris water maze...

Memory Reconsolidation Engages Only a Subset of Immediate-Early Genes Induced during Consolidation

“…Hippocampal SGK1 expression is induced by water maze training (Tsai et al, 2002) and environmental enrichment (Lee et al, 2003), a procedure known to improve hippocampus-dependent L&M (Duffy et al, 2001;Need and Giese, 2003). Furthermore, SGK1 is required for spatial memory formation in the water maze (Tsai et al, 2002). Similarly, zif268 is required for consolidation of object recognition memory (Jones et al, 2001;Bozon et al, 2003).…”

“…SGK1, for example, has recently been implicated in hippocampus-dependent learning and memory (L&M). Hippocampal SGK1 expression is induced by water maze training (Tsai et al, 2002) and environmental enrichment (Lee et al, 2003), a procedure known to improve hippocampus-dependent L&M (Duffy et al, 2001;Need and Giese, 2003). Furthermore, SGK1 is required for spatial memory formation in the water maze (Tsai et al, 2002).…”

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

“…95 Increased expression of Sgk1 has been observed in the Hippo of fast-learning rats as compared with slow-learning rats. 96 Enrichment-induced Sgk1 expression is specifically mediated through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors 97 and Sgk1 can directly phosphorylate the transcription factor cyclic AMP response element-binding protein (CREB) on serine 133. 98 Sgk1 expression level is increased by acute amphetamine 36 and lysergic acid diethylamide (LSD) treatment, 36 and it is increased in the brain and peripheral tissues following psychosocial stress.…”

“…101 Taken together, the published data and our own data strongly suggest a role for Sgk1 in stress, cell survival, and also learning and memory consolidation and other central functions, like reward and depression. 96,102 Sulfotransferase 1a (Sult1a1) specifically catalyzes the sulfonation of the catecholamines, dopamine, adrenaline and noradrenaline as well as of drugs such as apomorphine. Sult1a1 is involved in drug metabolism, cancer, hormone regulation and neurotransmitter synthesis/metabolism.…”

A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons

“…The current evidence points to a role of SGK1 in activity-dependent facilitation of learning and memory formation (16,17), consolidation of long-term memory (18), facilitation of expression of longterm potentiation in hippocampal neurons (19), and modulation of synaptic plasticity in the dorsal horn of the spinal cord (15).…”