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Antisense oligonucleotide inhibition of calcium/calmodulin-dependent protein kinase II and working memory deficits in the gerbil

Year: 2002
Type: dissertation
Abstract: It has been demonstrated that genetically engineered mice lacking calcium/calmodulin dependent protein kinase II α-subunit (CaM kinase) are impaired in working memory tasks.While this method has been useful in stimulating interest in the relationships, there are limitations to this technique.The relationship between CaM kinase and working memory was investigated by using a T-maze task in the present experiment.It was hypothesized that the AON group would make significantly more errors on a T-maze task than the gerbils injected with missense oligonucleotides.It was also predicted that animals treated with AON's would exhibit a reduction in CaM kinase α-subunit expression, but not CaM kinase β-subunit or actin.To inhibit CaM kinase, pretrained gerbils received intrahippocampal injections of antisense oligonucleotides complimentary to CaM kinase α-subunit (5 μM; 5'-GGTAGCCATCCTGGACT-3') or missense oligonucleotides (5 μM; 5'-GGTCGCCATCAGGTCACT-3'). Animals received three injections separated by 24 hrs.Six hours following the last injection, working memory was assessed by using a T-maze task.Animals were euthanized following behavioral testing and hippocampi were extracted and assayed.Hippocampal proteins were separated by SDS-PAGE and transferred to Immohilon-P membranes.Membranes were probed with a monoclonal antibody against CaM kinase (-α and β-subunits) and actin.Animals treated with AON's exhibited a small impairment in working memory and reduction in CaM kinase α-subunit expression.However, these differences were not statistically significant.The data failed to-support a role for CaM kinase in working memory.Possible explanations and future implications for these findings are discussed.
Language: English
Open Access status: green
OpenAlex ID: W43122481
Cites: 32
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Related to: 10