Biology subjects

Anderson, C. R.

Publications and source records attributed to Anderson, C. R..

3 recordsLinked to original sources

bioRxiv2022

Age-dependent dysregulation of locus coeruleus firing in a transgenic rat model of Alzheimers disease

Accumulation of hyperphosphorylated tau in the locus coeruleus (LC) is a ubiquitous feature of prodromal Alzheimers disease (AD), and LC neurons degenerate as AD progresses. Tau-mediated LC dysfunction may contribute to early neuropsychiatric symptoms, while loss of LC integrity is associated with conversion to cognitive impairment. Hyperphosphorylated tau alters firing rates in other brain regions, but its effects on LC neurons have not been described. The purpose of this study was to characterize changes in firing properties of LC neurons when they are the only cells containing hyperphosphorylated tau, as well as later in disease when {beta}-amyloid (A{beta}) and tau pathology is abundant in the forebrain. Single unit LC activity was recorded from anesthetized wild-type (WT) and TgF344-AD rats, which carry the APP/PS1 transgene. Similar to human AD, these rats develop hyperphosphorylated tau in the LC (at 6 months) prior to A{beta} or tau pathology in forebrain regions (at 12-15 months). At baseline, LC neurons from TgF344-AD rats were hypoactive at both ages compared to WT littermates, but showed elevated spontaneous bursting properties, particularly in younger animals. Differences in footshock-evoked LC firing depended on age, with 6-month TgF344-AD rats demonstrating aspects of hyperactivity, and aged transgenic rats showing hypoactivity relative to WT. Tau-induced alterations in LC firing rates may contribute to the pathophysiology of AD, with early hyperactivity associated with prodromal symptoms, followed by hypoactivity contributing to cognitive impairment. These results support further investigation into disease stage-dependent noradrenergic interventions for AD. HighlightsO_LIRecorded locus coeruleus (LC) neurons in a rat model of Alzheimers disease (AD) C_LIO_LITgF344-AD rats develop early endogenous LC tau pathology akin to human AD C_LIO_LI6- and 15-month TgF344-AD rats had reduced tonic LC firing C_LIO_LILC neurons from 6-month TgF344-AD rats were hyperactive in response to footshock C_LIO_LILC neuron dysfunction may contribute to AD symptoms C_LI

neuroscience↗

bioRxiv2022

Genomic correlates for migratory direction in a free-ranging cervid

Animal migrations are some of the most ubiquitous and one of the most threatened ecological processes. A wide range of migratory behaviours occur in nature, and this behaviour is not uniform between and within species, where even individuals in the same population can exhibit differentiation. While the environment largely drives migratory behaviour, it is necessary to understand the genetic mechanisms influencing migration to elucidate the adaptive potential of migratory species to cope with novel conditions and adapt to environmental change. In this study, we identified genes associated with migratory traits by undertaking pooled genome-wide scans on a natural population of a facultatively migrating ungulate. We identified genomic regions associated with variation in migratory direction in the study population, including FTM1, a gene linked to the formation of lipids, and DPPA3, a gene linked to epigenetic modifications of the maternal line. Such a genetic basis for migratory traits can have implications on heritability of behaviour and the flexibility of individuals to change their behaviour in the face of stochastic changes in their environment.

genomics↗

bioRxiv2021

Consequences of endogenous and virally-induced hyperphosphorylated tau on behavior and cognition in a rat model of Alzheimer's disease

BackgroundThe locus coeruleus (LC) is one of the earliest brain regions to accumulate hyperphosphorylated tau, but a lack of animal models that recapitulate this pathology has hampered our ability to understand its contributions to the pathophysiology of Alzheimers disease (AD). ObjectiveWe previously reported that TgF344-AD rats, which overexpress mutant human amyloid precursor protein and presenilin-1, accumulate early endogenous hyperphosphorylated tau in the LC. Here, we used TgF344-AD rats and a wild-type (WT) human tau virus to interrogate the effects of endogenous hyperphosphorylated rat tau and human tau in the LC on AD-related neuropathology and behavior. MethodsTwo-month old TgF344-AD and WT rats received bilateral LC infusions of WT human tau or mCherry control virus driven by the noradrenergic-specific PRSx8 promoter. Rats were subsequently assessed at 6 and 12 months for arousal (sleep latency), anxiety-like behavior (open field, elevated plus maze, novelty-suppressed feeding), passive coping (forced swim task), and learning and memory (Morris water maze and fear conditioning). Hippocampal microglia, astrocyte, and AD pathology were evaluated using immunohistochemistry. ResultsIn general, the effects of age were more pronounced than genotype or treatment; older rats displayed greater hippocampal pathology, took longer to fall asleep, had reduced locomotor activity, floated more, and had impaired cognition compared to younger animals. TgF344-AD rats showed increased anxiety-like behavior and impaired learning and memory. The tau virus had negligible influence on most measures. ConclusionEffects of hyperphosphorylated tau on AD-like neuropathology and behavioral symptoms were subtle. Further investigation of different forms of tau is warranted.

neuroscience↗