Metzendorf, N. | bioRxiv Science

bioRxiv2024

Pigment-dispersing factor neuropeptides act as multifunctional hormones and modulators in tardigrades

Pigment-dispersing factors (PDFs) are neuropeptides that play key roles in controlling the circadian rhythms in various insects, whereas their function remains elusive in other protostomes including tardigrades (water bears). Here we show that the three PDFs of the tardigrade Hypsibius exemplaris are co-localized in two pairs of inner lobe cells in the brain, whereas only one PDF occurs in four additional cerebral and two extracerebral cells. The axons of the inner lobe cells pass through the contralateral brain hemisphere, descend to the ventral nerve cord and terminate in two pairs of potential release sites in the posteriormost trunk ganglion. Using in vitro assays, we demonstrate that all three PDFs and their deorphanized receptor (PDFR) are functional. Widespread localization of PDFR suggests that tardigrade PDFs may act as multifunctional hormones and neuromodulators that control major functions including light detection, neural processing, locomotion, feeding, digestion, osmoregulation, growth, embryonic development, and oogenesis/reproduction.

zoology↗

bioRxiv2023

Effect of ketamine on early synaptic mistuning and emotional behavior deficits in AppNL-F mouse model of Alzheimer's disease.

Alzheimers disease is the most common neurodegenerative disease and constitute 75% of dementia cases worldwide. Unfortunately, efficient and affordable treatments are still lacking for this mental illness, it is therefore urgent to identify new pharmacological targets. Whereas the late phases of the disease are well described, recent evidence suggest synaptic impairments at a pre-amyloid {beta} (A{beta}) plaque stage. Astrocytes are playing a crucial role in the tuning of synaptic transmission and several studies have pointed out severe astrocyte reactivity in Alzheimers disease, especially around A{beta} plaques. Reactive astrocytes show altered physiology and function, suggesting they could have a role in the early pathophysiology of Alzheimers disease. In this study we used the AppNL-F knock-in mouse model of Alzheimers disease which carries two disease-causing mutations inserted in the amyloid precursor protein (App) gene. This strain does not start to develop A{beta} plaques until nine months of age. To better understand early changes in Alzheimers disease, we investigated synaptic function, at both neuronal and astrocytic levels, in six months old AppNL-F mice and correlate the synaptic dysfunction with emotional behavior. Electrophysiological recordings in the hippocampus revealed an overall synaptic mistuning at a pre-plaque stage of the pathology, associated to an intact social memory but a stronger depressive-like behavior. Astrocytes displayed a reactive-like morphology and a higher tonic GABA current compared to control mice. Interestingly, we here show that the synaptic impairments in hippocampal slices are partially corrected by a pre-treatment with the monoamine oxidase B (MAO-B) blocker deprenyl or the fast-acting antidepressant ketamine (5mg/kg). Thus, we propose that reactive astrocytes can induce synaptic mistuning early in Alzheimers disease, before plaques deposition, and that these changes are associated with emotional symptoms. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/540486v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@fb19a7org.highwire.dtl.DTLVardef@151454borg.highwire.dtl.DTLVardef@9c7a12org.highwire.dtl.DTLVardef@112633e_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

neuroscience↗