Biology subjects

van Rosmalen, L.

Publications and source records attributed to van Rosmalen, L..

3 recordsLinked to original sources

bioRxiv2026

The circadian system is affected by Alzheimers disease independently from amyloid beta deposits

Circadian disruption, notably sleep disturbances, serves as an early indicator of Alzheimers disease (AD), preceding cognitive symptoms like memory loss. The suprachiasmatic nucleus (SCN) governs biological rhythms and receives direct retinal input via melanopsin-expressing retinal ganglion cells (mRGCs) to synchronize with environmental light cycles. The anatomical and functional basis for circadian disruption in AD remains unclear. Here, we explored the multi-level relationships between gene expression, the SCN connectome, and regulations of sleep and circadian rhythms in the APP/PS1 mouse model. The sleep architecture of APP/PS1 mice displayed significantly reduced rapid eye movement sleep (REM), associated with a reduced daily core body temperature amplitude and locomotor hyperactivity. Lastly, APP/PS1 mice showed an impaired response to acute light pulse stimulation and present hyperactivity of mRGCs at a young age and hypoactivity of these cells at older ages. These physiological functions are known to be, at least in part, regulated by the SCN, the main target of mRGCs. We noted several modifications in SCN connectomics using serial blockface electron microscopy (SBEM), including a reduction of the dendro-dendritic chemical synapse (DDCS) network that receives a large part of the retinal input and is thought to be crucial for synchronicity between SCN neurons. In addition, we observed multiple signs of dystrophy, including modifications of the shape of dendrites and cell soma, accumulation of aggregated lysosomes, and swelling of axons. At the same time, we investigated the changes in gene expression using spatial transcriptomics. The SCN presents changes in the expression of genes associated with synapse formation, cell adhesion, and neurite growth. These results suggest that, despite the absence of amyloid plaques in the ventral hypothalamus, the SCN of APP/PS1 mice still undergo profound gene expression changes, impacting connectomics and physiological functions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/744599v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@ceedb0org.highwire.dtl.DTLVardef@156cfaaorg.highwire.dtl.DTLVardef@5bc262org.highwire.dtl.DTLVardef@36df4d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Food and temperature change photoperiodic responses in two vole species: different roles for hypothalamic genes

Seasonal timing of reproduction in voles is driven by photoperiod. Here we hypothesize that a negative energy balance can modify spring-programmed photoperiodic responses in the hypothalamus, controlling reproductive organ development. We manipulated energy balance by the work-for-food protocol, in which voles were exposed to increasing levels of food scarcity at different ambient temperatures under long photoperiod. We reveal that common (Microtus arvalis) and tundra voles (Microtus oeconomus), reduce photoperiodic induced pars tuberalis thyroid-stimulating hormone {beta}-subunit (Tsh{beta}) expression to inhibit gonadal development when food is scarce. Reduction in gonadal size is more pronounced in tundra voles, in which the hypothalamic Kisspeptin (Kiss1) system seems involved in downregulating gonadal development, especially in males. Low temperature additionally leads to decreased hypothalamic RF-amide related peptide (Rfrp3) levels, which may facilitate further suppression of gonadal growth. Shutting off the photoperiodic-axis when food is scarce in spring may be an adaptive response to save energy, leading to delayed reproductive organ development until food resources are sufficient for reproduction, lactation and offspring survival. Defining the mechanisms through which metabolic cues modify photoperiodic responses will be important for a better understanding of how environmental cues impact reproduction. Summary statementThis study provides a better understanding of the molecular mechanism through which metabolic cues can modify photoperiodic responses, to adaptively adjust timing of reproductive organ development

neuroscience↗

bioRxiv2020

Gonads or body? Differences in gonadal and somatic photoperiodic growth response in two vole species.

To optimally time reproduction, seasonal mammals use a photoperiodic neuroendocrine system (PNES) that measures photoperiod and subsequently drives reproduction. To adapt to late spring arrival at northern latitudes, a lower photoperiodic sensitivity and therefore a higher critical photoperiod for reproductive onset is necessary in northern species to arrest reproductive development until spring onset. Temperature-photoperiod relationships, and hence food availability-photoperiod relationships, are highly latitude dependent. Therefore, we predict PNES sensitivity characteristics to be latitude-dependent. Here, we investigated photoperiodic responses at different times during development in northern- (tundra/root vole, Microtus oeconomus) and southern vole species (common vole, Microtus arvalis) exposed to constant short (SP) or long photoperiod (LP). M. oeconomus grows faster under LP, whereas no photoperiodic effect on somatic growth is observed in M. arvalis. Contrastingly, gonadal growth is more sensitive to photoperiod in M. arvalis, suggesting that photoperiodic responses in somatic and gonadal growth can be plastic, and might be regulated through different mechanisms. In both species, thyroid-stimulating-hormone-{beta} subunit (Tsh{beta}) and iodothyronine-deiodinase 2 (Dio2) expression is highly increased under LP, whereas Tshr and Dio3 decreases under LP. High Tshr levels in voles raised under SP may lead to increased sensitivity to increasing photoperiods later in life. The higher photoperiodic induced Tshr response in M. oeconomus suggests that the northern vole species might be more sensitive to TSH when raised under SP. Species differences in developmental programming of the PNES, which is dependent on photoperiod early in development, may form part divergent breeding strategies evolving as part of latitudinal adaptation. Summary statementDevelopment of the neuroendocrine system driving photoperiodic responses in gonadal and somatic growth differ between the common and the tundra vole, indicating that they use a different breeding strategy.

neuroscience↗