Biomedical subjects

K Peter Giese

Publications and source records attributed to K Peter Giese.

22 records · Page 2Linked to original sources

PubMed2003

Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression.

Cleavage of the cyclin-dependent kinase 5 activator p35 generates the protein fragment p25, which accumulates in the forebrain of patients with Alzheimer's disease. Although p25 expression has been suggested to affect learning and memory, this hypothesis has not been tested to date. To investigate the role of p25 in hippocampus-dependent learning and memory we have generated transgenic mice expressing p25 preferentially in postnatal forebrain. p25 expression was highest in hippocampus where it averaged approximately 33% of endogenous p35 expression. This low level of p25 expression did not seem to result in hyperphosphorylation of tau, but increased the phosphorylation of neurofilament M and enhanced the expression of tau protein. These molecular changes did not correlate with neurodegeneration or motor abnormalities. In the Morris water maze the p25 mutants were normal in learning an initial platform location, but surprisingly reversal learning was improved when the platform position was changed. The p25 mutants were normal in contextual fear conditioning. However, when trained with a tone presentation the mutants showed reduced contextual conditioning and enhanced tone fear conditioning. We conclude that low p25 expression has pleiotropic effects on learning and memory. As p25 expression can improve learning and memory, p25 formation could be a compensatory mechanism for learning and memory deficits in Alzheimer's disease.

Alzheimer Disease↗

PubMed2003

Learning and memory impairments in Kv beta 1.1-null mutants are rescued by environmental enrichment or ageing.

Mice with a null mutation of the K+ channel regulatory subunit Kv beta 1.1 have altered excitability in hippocampal neurons and are impaired in the social transmission of food preferences (STFP) task. It was previously unclear whether this impairment is related to learning and memory (L & M) deficits or to developmental abnormalities. In this study we show that rearing the Kv beta 1.1 mutants in an enriched environment rescues the impairment in the STFP task. Furthermore, we found that STFP performance was impaired in 12-month-old wild-type mice, but not in the Kv beta 1.1 mutants at this age, indicating that the Kv beta 1.1 mutants show an age-related rescue of the deficits observed in the young mutants. Ibotenic acid lesions of the hippocampus in the 12-month-old Kv beta 1.1 mutants caused an impairment in the STFP task. Our findings indicate that performance in the STFP task is age-dependent and involves the hippocampus. Furthermore, we have established that the impairments in the Kv beta 1.1 mutants are related to L & M and not to performance disabilities. Finally, we suggest that the loss of Kv beta 1.1 function is beneficial for L & M in middle age.

Aging↗

PubMed2003

Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice.

It has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long-term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin-1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin-1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin-1 receptor knockout mice. Neurogenesis can be increased in wild-type but not neurokinin-1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain-derived neurotrophic factor are also two-fold higher in neurokinin-1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus-dependent learning and memory but found no clear enhancement in neurokinin-1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain-derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain-derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy.

Animals↗

PubMed2003

Contextual fear conditioning regulates the expression of brain-specific small nucleolar RNAs in hippocampus.

Some small nucleolar RNAs (snoRNAs) are exclusively expressed in the brain but they have no known role in higher brain function. We analysed the expression pattern of four brain-specific snoRNAs: MBI-36, MBII-48, MBII-52 and MBII-85, in mouse brain using in situ hybridization. All of these genes were expressed in the hippocampus and, except for MBII-85, their levels in ventral parts were higher than those in dorsal parts. Using quantitative real-time polymer chain reaction we determined hippocampal expression changes after contextual fear conditioning in mice. Ninety minutes, but not 25 h, after conditioning, we observed significant downregulation of MBII-48 and upregulation of MBII-52. Our finding that the expression of MBII-48 and MBII-52 is regulated during learning suggests that these snoRNAs have an important role in higher brain function.

Animals↗