Biomedical subjects

Olof Wiegert

Publications and source records attributed to Olof Wiegert.

4 recordsLinked to original sources

PubMed2006

Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy.

The microtubule binding protein tau is implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by diverse mutations in the tau gene. Hyperphosphorylation of tau is considered crucial in the age-related formation of neurofibrillary tangles (NFTs) correlating well with neurotoxicity and cognitive defects. Transgenic mice expressing FTD mutant tau-P301L recapitulate the human pathology with progressive neuronal impairment and accumulation of NFT. Here, we studied tau-P301L mice for parameters of learning and memory at a young age, before hyperphosphorylation and tauopathy were apparent. Unexpectedly, in young tau-P301L mice, increased long-term potentiation in the dentate gyrus was observed in parallel with improved cognitive performance in object recognition tests. Neither tau phosphorylation, neurogenesis, nor other morphological parameters that were analyzed could account for these cognitive changes. The data demonstrate that learning and memory processes in the hippocampus of young tau-P301L mice are not impaired and actually improved in the absence of marked phosphorylation of human tau. We conclude that protein tau plays an important beneficial role in normal neuronal processes of hippocampal memory, and conversely, that not tau mutations per se, but the ensuing hyperphosphorylation must be critical for cognitive decline in tauopathies.

Animals↗

PubMed2006

Timing is essential for rapid effects of corticosterone on synaptic potentiation in the mouse hippocampus.

Stress facilitates memory formation, but only when the stressor is closely linked to the learning context. These effects are, at least in part, mediated by corticosteroid hormones. Here we demonstrate that corticosterone rapidly facilitates synaptic potentiation in the mouse hippocampal CA1 area when high levels of the hormone and high-frequency stimulation coincide in time, but not when corticosterone is given either before or after repetitive stimulation. This effect could not be blocked by antagonists of the mineralocorticoid receptor and glucocorticoid receptor (spironolactone and RU 38486, respectively). These data provide a biological substrate for the important behavioral observation that stress and corticosteroid hormones can facilitate learning and memory processes.

Analysis of Variance↗

PubMed2006

Learning under stress: how does it work?

The effects of stress on learning and memory are not always clear: both facilitating and impairing influences are described in the literature. Here we propose a unifying theory, which states that stress will only facilitate learning and memory processes: (i) when stress is experienced in the context and around the time of the event that needs to be remembered, and (ii) when the hormones and transmitters released in response to stress exert their actions on the same circuits as those activated by the situation, that is, when convergence in time and space takes place. The mechanism of action of stress hormones, particularly corticosteroids, can explain how stress within the context of a learning experience induces focused attention and improves memory of relevant information.

Animals↗

PubMed2006

Stress, corticosteroid hormones and hippocampal synaptic function.

Exposure to stressful events has profound impact on hippocampus-dependent learning and memory processes. Traumatic and stressful experiences are remembered well in general, but have also been reported to suppress learning and memory processes. These bi-directional effects are, at least in part, modulated by corticosteroid hormones that are released during exposure to stressful experiences. An important question that remains to be addressed is how exactly exposure to stressful situations and elevated corticosteroid hormone levels affect learning and memory processes. Evidence is accumulating that exposure to stressful situations and elevated corticosteroid hormone levels modulates fast excitatory amino acid mediated synaptic transmission and synaptic plasticity, which are considered to underlie learning and memory processes in the hippocampus. In particular, exposure to stressful events has been reported to facilitate synaptic plasticity when delivered shortly before or after high frequency stimulation. By contrast, stressful events and elevated corticosteroid hormones suppress synaptic potentiation when stress precedes high frequency stimulation. From the mechanistic point of view, it is potentially important that exposure to stressful events and elevated corticosteroid hormone levels target key mechanisms that are involved in synaptic plasticity, i.e. AMPA receptors and NMDA receptors.

Adrenal Cortex Hormones↗