Biology subjects

Yildirim, T.

Publications and source records attributed to Yildirim, T..

6 recordsLinked to original sources

bioRxiv2026

Standard touchscreen test procedures shift circadian rhythms in mice: a modified protocol to minimize circadian confounds

Touchscreen based cognitive testing for rodents offers considerable experimental benefits, including a semi automated battery approach and the use of appetitive rather than aversive reinforcement. However, food reward and touchscreen illumination introduce potential confounds, as both food and light can shift, entrain, or disrupt circadian rhythms, which in turn can affect learning and memory. The potential for the test apparatus to impact endogenous circadian rhythms is particularly problematic when probing relationships between sleep, circadian disruption, and cognitive performance. After observing phase shifting of circadian rhythms in nocturnal mice tested using standard touchscreen test procedures, which include testing during the active period (early lights off), we evaluated the relative contributions of the illuminated screen and the appetitive food reward. Our results indicate that light emitted by the touchscreen chambers is responsible for the circadian phase shifting effects, with standard screen conditions inducing a ~3.5 h phase delay in daily activity rhythms when training is conducted early in the dark period for 7 consecutive days. We then modified lighting in the test environment and the home cage to identify parameters that would minimize circadian shifting without impairing visual discrimination or performance on a widely used cognitive test (Trial Unique Nonmatching to Location, TUNL). From the 10 conditions tested, we offer specific recommendations for modifying touchscreen test protocols to minimize circadian confounds, without impacting task acquisition or performance.

animal behavior and cognition↗

bioRxiv2026

Modelling shiftwork and sleep fragmentation in mice: behavioural phenotypes and implications for hippocampal neurogenesis

Sleep disturbances compromise cognition, and overall physical and mental health; however, animal models of these effects remain limited, and typically impose more extreme disturbances than those experienced by humans. Here, we use behavioural interventions in mice to model two common types of sleep disruption: (1) sleep displacement associated with shiftwork and (2) sleep fragmentation associated with aging and disease. C57BL6/J mice were subjected to either a sleep deprivation protocol (n = 8, females = 4) or a fragmentation protocol (n = 8, females = 4), in which they were completely deprived of sleep or awoken every 2 min respectively, for 12 hours during their typical rest phase (lights-on) across 7 consecutive days. Age-matched control mice (n = 14, females = 7) remained undisturbed in their home cages. Activity during the 12-hour active phase was recorded via infrared motion sensors. After protocol completion, mice were injected with bromodeoxyuridine (BrdU, 200mg/kg) 2 hours prior to brain and blood collection; hippocampal neurogenesis and plasma corticosterone were then assessed. Results show that the sleep deprivation and fragmentation protocols had different, dynamic effects on behaviour; sleep deprivation was associated with an accumulating sleep need, operationalized as progressively reduced locomotor activity across the week, whereas fragmentation produced only an acute reduction of locomotor activity. Cell proliferation rates and corticosterone did not differ from controls. These protocols provide a foundation for future research into the mechanistic links between shiftwork and sleep fragmentation on health and cognition.

neuroscience↗

bioRxiv2026

Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimer's disease

Sleep disturbance in Alzheimers disease (AD), particularly the reduction of slow wave sleep (SWS), has been proposed as a novel therapeutic target, with disease-modifying potential. Trazodone, an antidepressant with robust SWS-promoting properties, is currently the most prescribed sleep-promoting medication in the United States. Here, we demonstrate that chronic trazodone administration consolidates sleep in the APPNL-F knock-in mouse model of AD, increasing NREM sleep duration and slow wave power during the rest phase while promoting wake during the active phase. These sleep consolidating effects were accompanied by lower regional glial activation and amyloid burden, particularly in male mice. Most notably, hippocampal amyloid plaque burden was 45% lower in mice treated from 14 to 16 months of age than in vehicle-treated controls. Chronic trazodone treatment was also associated with better short-term and long-term recognition memory. Together, these findings support the potential of repurposing trazodone as a well-tolerated, disease-modifying therapeutic for AD, capable of enhancing sleep quality, improving cognition, and lowering AD-relevant neuropathology.

neuroscience↗

bioRxiv2026

Repeated mild traumatic brain injury does not affect sleep or epileptiform activity one-month post-injury in a knock-in mouse model of Alzheimer's disease

Traumatic brain injuries (TBIs) are associated with increased risk of neurodegenerative disease, including Alzheimers disease (AD); however, the mechanisms by which TBI promotes AD pathogenesis remain poorly understood. It also remains unclear whether post-TBI sequelae, including sleep disturbances and seizures, play a role in driving disease progression. To investigate these relationships, we employed a translational approach using the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) of repeated mild TBI (rmTBI) and an AD knock-in mouse model to assess sleep, power spectral density, epileptiform activity, and A{beta} pathology one month post-injury. RmTBI caused elevated neurofilament-light and glial fibrillary acidic protein, markers of neuronal damage. Sex differences were observed in acute injury outcomes, sleep measures, and A{beta} plaque size. Specifically, females exhibited longer recovery post-injury, higher mortality, decreased non-rapid eye movement sleep duration, and larger average plaque size than males at equivalent impact energy. These findings highlight the importance of including both sexes when establishing injury severity thresholds. Future studies should incorporate validated TBI biomarkers of neural injury to define equivalent injury parameters across sexes and examine the chronic effects of rmTBI on sleep, epileptiform activity and AD pathology.

neuroscience↗

bioRxiv2025

Repetitive mild traumatic brain injury causes neuronal damage in the APP/PS1 mouse model of Alzheimer's disease without an enduring impact on amyloid pathology, sleep, or epileptiform activity

Traumatic Brain Injury (TBI) is a known risk factor for Alzheimers disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the development of neuropathology. In this study, we characterized sleep, epileptiform activity, and neuropathology after repetitive mild traumatic brain injury (rmTBI) in a mouse model of Alzheimers disease. We used the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) to deliver rmTBI or sham (control) treatment to 6-month-old APP/PS1 mice (N=19). One month post-injury, we implanted electroencephalogram (EEG) and electromyographic (EMG) electrodes, recorded for 72 hours, and then collected brain tissue and blood plasma. Our assessment of sleep architecture showed that time spent in vigilance state was not affected by the rmTBI one month post-injury; however, power spectra analysis showed a shift towards higher frequencies in the rmTBI group during non-rapid eye movement (NREM) sleep. Epileptiform activity did not differ between sham and rmTBI. Compared to sham controls, the rmTBI group showed higher neurofilament light (NF-L), but not glial-fibrillary acidic protein (GFAP) in blood plasma and no change in A{beta} pathology. These results indicate sustained neurological injury in the APP/PS1 mice one month after rmTBI without affecting amyloid deposition in the brain. Our study suggests that rmTBI can induce neural injury without causing enduring sleep disruption, seizures, and exacerbation of amyloidosis in the APP/PS1 mouse model.

neuroscience↗

bioRxiv2019

A low-cost and high-precision scanning electrochemical microscope built with open source tools

A low-cost Scanning Electrochemical Microscope (SECM) was built with a 0.6 pA current measurement capability potentiostat and submicron resolution motorized stage, using open source software and hardware tools. The high performance potentiostat with a Python graphical user interface was built based on an open source project. Arduino boards, stepper motors, a manual XY micromanipulator stage, 3D printed couplers and gears were used in building the motorized stage. An open source motor control software was used for moving the motorized stage with high precision. An inverted microscope was utilized for viewing a standard microelectrode while scanning. The setup was tested in the formation of a map of electrochemical signals from an array of pores on a parafilm membrane. As the setup will be used in future biosensing experiments, DNA hybridization detection experiments were also performed with the setup.

biochemistry↗