Biology subjects

Tisdale, R. K.

Publications and source records attributed to Tisdale, R. K..

3 recordsLinked to original sources

bioRxiv2026

Early origin of sugar sensing in jawed vertebrates

Sweet taste guides animals to consume carbohydrate-rich foods, and many different vertebrate groups, from fish to mammals, rely on sugar-rich fruits or nectar produced by flowering plants (angiosperms). Although the genes encoding T1R2-T1R3, the receptor pair that mammals use to sense sugars, exist in the genomes of many vertebrates, their functions are unclear--and whether sugar sensing arose once early in vertebrate evolution or independently in different lineages after angiosperms evolved is currently unknown. Here, we combined ancestral reconstruction and receptor functional profiling to examine the evolutionary history of T1R taste receptors--including recently-described non-canonical receptors--across all major vertebrate clades. Our results pinpoint the origin of sugar sensing to before the emergence of angiosperms and uncover a myriad of alternative T1R-based sugar-sensing mechanisms, suggesting multiple independent T1R trajectories and revealing uncharted sensory diversity across vertebrates.

evolutionary biology↗

bioRxiv2025

Sleep-Wake Transitions Are Impaired in the AppNL-G-FMouse Model of Early Onset Alzheimers Disease

Poor sleep quality and reduced sleep duration are associated with Alzheimers disease (AD)-related {beta}-amyloid (A{beta}) pathologies. We conducted two studies of sleep/wake, activity and body temperature in AppNL-G-F mice, a strain that exhibits three mutations in the human App gene associated with elevated risk for early onset AD. First, AppNL-G-F mice were compared to wildtype (WT) littermates at 14-18 and 18-22 months of age and, at both ages, were found to exhibit more Wake and less NREM and REM sleep than WT littermates. This long wake/short sleep phenotype was evident during the dark phase at 14-18 months but occurred in both the light and dark phases at 18-22 months. AppNL-G-F mice had fewer short (<60 sec) and more long (>260 sec) Wake bouts and were hyperactive at 18-22 months, which undoubtedly contributed to the increased Wake/reduced sleep. Despite this reduced sleep phenotype, AppNL-G-F mice were no sleepier than WT mice and the sleep homeostat was functional in both strains. In the second study, sex differences in these parameters were assessed at 18-24 months. Reduced sleep was evident in both sexes of AppNL-G-F mice but was clearly more evident in females. Wake and REM sleep bout durations were longer in both sexes of AppNL-G-F mice than in WT littermates. EEG spectral power during NREM sleep was reduced in female AppNL-G-F mice between 4.88-10.50 Hz compared to WT mice whereas, during REM sleep, both male and female AppNL-G-F mice exhibited reduced spectral power in the theta range. These results suggest that A{beta} deposition may impair state transition mechanism(s) in AppNL-G-F mice and demonstrate that, as in human AD patients, the long wake/short sleep phenotype was more evident in female AppNL-G-F mice, thus supporting the use of this strain as a model to investigate interventions that mitigate AD burden during early disease stages.

neuroscience↗

bioRxiv2022

Evaluation of the Efficacy of the Hypocretin/orexin Receptor Agonists TAK-925 and ARN-776 in Narcoleptic Orexin/tTA; TetO-DTA Mice

The sleep disorder Narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK- 925 (1-10 mg/kg, s.c.) and ARN-776 (1-10 mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc) and activity were recorded by telemetry; recordings for the first 6-h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the 2nd hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6-h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterized by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the 2nd hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity and Tsc, suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HcrtR2 agonists.

neuroscience↗