Biology subjects

Petersen, S.

Publications and source records attributed to Petersen, S..

3 recordsLinked to original sources

bioRxiv2018

Tauopathy in the APPswe/PS1ΔE9 mouse model of familial Alzheimer’s disease

Despite compelling evidence that the accumulation of amyloid-beta (A{beta}) promotes cortical MAPT (tau) aggregation in familial and idiopathic Alzheimers disease (AD), murine models of cerebral amyloidosis are not considered to develop tau-associated pathology. The absence of neurofibrillary lesions in amyloidosis mice remains a challenge for the amyloidocentric paradigm of AD pathogenesis. It has resulted in the generation of transgenic mice harboring mutations in their tau gene, which may be inappropriate for studying a disease with no known TAU mutations, such as AD. Here, we have used APPswe/PS1{Delta}E9 mice to show that tau pathology can develop spontaneously in murine models of familial AD. Tauopathy was abundant around A{beta} deposits, with Gallyas- and thioflavin-S-positive perinuclear inclusions accumulating in the APPswe/PS1{Delta}E9 cortex by 18 months of age. Age-dependent increases in Gallyas signal correlated positively with binding levels of the paired helical filament (PHF) ligand [18F]Flortaucipir, in all brain areas examined. Sarkosyl-insoluble PHFs were visualized by electron microscopy. Tandem mass tag proteomics identified sequences of hyperphosphorylated tau in transgenic mice, along with signs of RNA missplicing, ribosomal dysregulation and disturbed energy metabolism. Human frontal gyrus tissue was used to validate these findings, revealing primarily quantitative differences between the tauopathy observed in AD patient vs. transgenic mouse tissue. Levels of tau mRNA were not different between APPswe/PS1{Delta}E9 and littermate control animals. As physiological levels of endogenous, wild-type tau aggregate secondarily to A{beta} in transgenic mice, this study demonstrates that amyloidosis is both necessary and sufficient to drive tauopathy in experimental models of familial AD.

neuroscience↗

bioRxiv2017

A rainfall-manipulation experiment with 517 Arabidopsis thaliana accessions

The gold standard for studying natural selection and adaptation in the wild is to quantify lifetime fitness of individuals from natural populations that have been grown together in a common garden, or that have been reciprocally transplanted. By combining fitness values with species traits and genome sequences, one can infer selection coefficients at the genetic level. Here we present a rainfall-manipulation experiment with 517 whole-genome sequenced natural accessions of the plant Arabidopsis thaliana spanning the global distribution of the species. The experiments were conducted in two field stations in contrasting climates, in the Mediterranean and in Central Europe, where we built rainout shelters and simulated high and low rainfall. Using custom image analysis we quantified fitness- and phenology-related traits for 23,154 pots, which contained about 14,500 plants growing independently, and over 310,000 plants growing in small populations (max. 30 plants). This large field experiment dataset, which associates fitness and ecologically-relevant traits with genomes, will provide an important resource to test eco-evolutionary genetic theories and to understand the potential evolutionary impacts of future climates on an important plant model species.

evolutionary biology↗

bioRxiv2017

Parasympathetic and sympathetic activity are associated with individual differences in neural indices of selective attention in adults

Multiple theoretical frameworks posit that interactions between the autonomic nervous system and higher-order neural networks are crucial for cognitive regulation. However, few studies have directly examined the relationship between measures of autonomic physiology and brain activity during cognitive tasks, and fewer studies have examined both the parasympathetic and sympathetic autonomic branches when doing so. Here, 93 adults completed an event-related potential (ERP) auditory selective attention task concurrently with measures of parasympathetic activity (high-frequency heart rate variability; HF-HRV) and sympathetic activity (pre-ejection period; PEP). We replicate previous findings showing effects of selective attention on mean amplitude of the N1 ERP component (Hillyard et al., 1973; Coch et al., 2005), and extend this result to show that the effects of selective attention were associated with baseline values of HF-HRV and PEP. Individuals with higher resting HF-HRV and shorter resting PEP showed larger effects of selective attention on their ERPs. Follow-up regression models demonstrated that HF-HRV and PEP accounted for unique variance in selective attention effects on N1 mean amplitude. These results are consistent with the neurovisceral integration model, which posits that greater parasympathetic activity is a marker of increased cognitive capacity, as well as other theoretical models which emphasize the role of heightened sympathetic activity in more efficient attention-related processing. The present findings highlight the importance of autonomic physiology in the study of individual differences in neurocognitive function, and given the foundational role of selective attention across cognitive domains, suggest that both parasympathetic and sympathetic activity may be key to understanding variability in brain function across a variety of cognitive tasks.

neuroscience↗