Biology subjects

Ghiani, C. A.

Publications and source records attributed to Ghiani, C. A..

4 recordsLinked to original sources

bioRxiv2025

Dissociating the Effects of Light at Night from Circadian Misalignment in a Neurodevelopmental Disorder Mouse Model Using Ultradian Light-Dark Cycles.

Individuals with neurodevelopmental disorders (NDDs) often experience sleep disturbances and are frequently exposed to light during nighttime hours. Our previous studies using the Cntnap2 knockout (KO) mouse model of NDDs demonstrated that nighttime light exposure increases behaviors such as excessive grooming, reduces social interactions, and disrupts daily locomotor rhythms. To further evaluate the effects of nighttime light exposure, we exposed wild-type (WT) and Cntnap2 KO mice to an ultradian lighting cycle (T7), which alternates 3.5 hours of light and 3.5 hours of darkness. Circadian rhythms in activity, corticosterone levels, and clock gene expression are maintained under T7 lighting despite the presence of light during the usual night phase, whilst animals display increased depressive-like behaviors and reduce performance on the novel object recognition test. Based on these observations, we hypothesized that T7 lighting would mimic the impact of nighttime light exposure seen in standard light-dark cycles with dim light at night (DLaN). However, in this study, adult WT and Cntnap2 KO mice held under the T7 cycle did not show the increased grooming behavior or reduced social interaction observed in Cntnap2 KO mice exposed to DLaN. Regarding locomotor activity rhythms, the T7 cycle lengthened the circadian period and weakened the rhythm amplitude but did not abolish rhythmicity in either genotype. Finally, opposite to DLaN, neither the T7 cycle nor constant darkness (DD) elicited an increase in cFos expression in the basolateral amygdala in WT and KO mice. These results demonstrate that the adverse behavioral and neurobiological effects of nighttime light exposure in a model of a neurodevelopmental disorder depend on circadian disruption rather than light exposure alone, highlighting the importance of circadian stability as a protective factor in NDDS.

neuroscience↗

bioRxiv2024

Scheduled feeding improves behavioral outcomes and reduces inflammation in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS), a leading inherited cause of intellectual disability and autism, is frequently accompanied by sleep and circadian rhythm disturbances. In this study, we comprehensively characterized these disruptions and evaluated the therapeutic potential of a circadian-based intervention in the fragile X mental retardation 1 (FMR1) knockout (KO) mouse. The Fmr1 KO mice exhibited fragmented sleep, impaired locomotor rhythmicity, and attenuated behavioral responses to light, linked to an abnormal retinal innervation and reduction of light-evoked neuronal activation in the suprachiasmatic nucleus. Behavioral testing revealed significant deficits in social memory and increased repetitive behaviors in the mutants, which correlated with sleep fragmentation. Remarkably, a scheduled feeding paradigm (6-hour feeding/18-hour fasting) significantly enhanced circadian rhythmicity, consolidated sleep, and improved social deficits and repetitive behaviors in the Fmr1 KO mice. This intervention also normalized the elevated levels of some pro-inflammatory cytokines, including IL-12 and IFN-{gamma}, in the mutants blood, suggesting that its benefits extend to inflammatory pathways. These findings highlight the interplay between circadian disruption, behavior, and an inflammatory response in FXS, and provide compelling evidence that time-restricted feeding may serve as a promising non-pharmacological approach for improving core symptoms in neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Sex Differences in Sleep Phenotypes in the BACHD Mouse Model of Huntington's Disease

Sleep and circadian rhythm disturbances are common features of Huntingtons disease (HD). HD is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies as well as preclinical work indicate there may be sex differences in disease progression. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s), we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in sleep/wake cycles are detectable in an animal model of the disease. Electroencephalography/electromyography (EEG/EMG) was used to measure sleep/wake states and polysomnographic patterns in young adult (12 week-old) male and female wild-type and BACHD mice. Our findings show that male, but not female, BACHD mice exhibited increased variation in phases of the rhythms as compared to age and sex matched wild-types. For both Rapid-eye movement (REM) and Non-rapid eye movement (NREM) sleep, genotypic and sex differences were detected. In particular, the BACHD males spent less time in NREM and exhibited a more fragmented sleep than the other groups. Both male and female BACHD mice exhibited significant changes in delta but not in gamma power compared to wild-type mice. Finally, in response to a 6-hrs sleep deprivation, both genotypes and sexes displayed predicted homeostatic responses to sleep loss. These findings suggest that females are relatively protected early in disease progression in this HD model. Significance StatementSleep and circadian rhythm disturbances are common features of Huntingtons disease (HD). Using an animal model of HD and EEG measures of sleep, we found that the males were more vulnerable to sleep/wake architecture alterations and sleep fragmentation. Homeostatic recovery from sleep loss did not appear to be altered at this stage of the disease. These findings raise the possibility that sex-specific factors play a role in the HD symptom progression and that hormone-based treatments may have therapeutic utility.

neuroscience↗

bioRxiv2022

Long wavelength light reduces the negative consequences of dim light at night in the Cntnap2 mouse model of autism.

Many patients with autism spectrum disorders (ASD) show disturbances in their sleep/wake cycles, and may be particularly vulnerable to the impact of circadian disruptors. We have previously shown that exposure to dim light at night (DLaN) in contactin associated protein-like 2 knock out (Cntnap2 KO) mice disrupts diurnal rhythms, increases repetitive behaviors while reducing social interactions. These negative effects of DLaN may be mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which is maximally sensitive to blue light (480nm). In this study, we used a light-emitting diode (LED) array that enabled us to shift the spectral properties of the DLaN while keeping the intensity at 10 lx. First, using wild-type (WT) mice, we confirmed that the short-wavelength enriched lighting produced strong acute suppression of locomotor activity (masking), robust light-induced phase shifts, and c-Fos expression in the suprachiasmatic nucleus, while the long-wavelength enriched lighting evoked much weaker responses. Furthermore, exposure of WT mice to the short-wavelength light at night reduced the amplitude of locomotor activity rhythms and impaired social interactions. Mice lacking the melanopsin expressing ipRGCs (Opn4DTA mice) were resistant to these negative effects of DLaN. Importantly, the shift of the DLaN stimulus to longer wavelengths ameliorated the negative impact on the activity rhythms and autistic behaviors (i.e. reciprocal social interactions, repetitive grooming) of the Cntnap2 KO model. The short-, but not the long-wavelength enriched, DLaN triggered cFos expression in the peri-habenula region as well as in the basolateral amygdala (BLA). Finally, DLaN-driven c-Fos induction in BLA glutamatergic neurons was about 3-fold higher in the Cntnap2 KO mice, suggesting that these cells may be particularly vulnerable to the effects of photic disruption. Broadly, our findings suggest that the spectral properties of light at night should be considered in the management of ASD and other neurodevelopmental disorders.

neuroscience↗