A5034858310- Sleep and Wakefulness Research
- Optical Imaging and Spectroscopy Techniques
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience of respiration and sleep
- Neuroscience and Neuropharmacology Research
- Photoacoustic and Ultrasonic Imaging
- Sleep and related disorders
- Circadian rhythm and melatonin
- Neurological disorders and treatments
- Neonatal and fetal brain pathology
- Neurotransmitter Receptor Influence on Behavior
- EEG and Brain-Computer Interfaces
- Traumatic Brain Injury and Neurovascular Disturbances
- Nuclear Receptors and Signaling
- Growth Hormone and Insulin-like Growth Factors
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Diet and metabolism studies
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Regulation of Appetite and Obesity
- Traumatic Brain Injury Research
- Nerve injury and regeneration
- Sleep and Work-Related Fatigue
- Pluripotent Stem Cells Research
University Hospital of Zurich
2015-2025
University of Zurich
2016-2025
University of Bern
2023-2024
Fundación Ciencias Exactas y Naturales
2003-2016
Consejo Nacional de Investigaciones Científicas y Técnicas
2006-2016
University of Buenos Aires
2010-2016
Instituto de Biomedicina y Genética Molecular de Valladolid
2013
Experimental Medicine and Biology Institute
2006-2011
Growing evidence from Alzheimer disease supports a potentially beneficial role of slow-wave sleep in neurodegeneration. However, the importance Parkinson is unknown. In 129 patients with disease, we retrospectively tested whether slow waves, objectively quantified polysomnography, relate to longitudinal changes Unified Parkinson's Disease Rating Scale motor scores. We found that higher accumulated power waves was associated slower progression, particularly axial symptoms, over mean time 4.6...
Improving sleep in murine Alzheimer's disease (AD) is associated with reduced brain amyloidosis. However, the window of opportunity for successful sleep-targeted interventions, regarding reduction pathological hallmarks and related cognitive performance, remains poorly characterized. Here, we enhanced slow-wave activity (SWA) during via sodium oxybate (SO) oral administration 2 weeks at early (6 months old) or moderately late (11 stages Tg2576 mice evaluated resulting neuropathology...
Understanding sleep and its perturbation by environment, mutation, or medication remains a central problem in biomedical research. Its examination animal models rests on brain state analysis via classification of electroencephalographic (EEG) signatures. Traditionally, these states are classified trained human experts visual inspection raw EEG recordings, which is laborious task prone to inter-individual variability. Recently, machine learning approaches have been developed automate this...
Slow-wave modulation alters synuclein accumulation and regulates proteostatic pathways in Parkinson’s disease mice.
Abstract Purpose Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer’s disease and frontotemporal dementia. High-resolution imaging of deposits at whole-brain scale animal models is highly desired. Methods We approached this challenge by non-invasively brains P301L mice 4-repeat with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) ~ 115 μm spatial resolution using tau-targeted pyridinyl-butadienyl-benzothiazole derivative...
Abstract The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature human gene and genetic association with attention deficit hyperactivity disorder (ADHD). Several efforts have been undertaken to determine D4R expression pattern in brain using immunohistochemistry, binding autoradiography situ hybridization, but overall published results present large discrepancies. Here, we explored an...
Abstract Abnormal alpha‐synuclein (αSyn) and iron accumulation in the brain play an important role Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions deposition brains of M83 (A53T) mouse models PD vivo. The fluorescent pyrimidoindole derivative THK‐565 probe was characterized by means recombinant fibrils from 10‐ 11‐month‐old mice. Concurrent wide‐field fluorescence volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed Structural...
Traumatic brain injury significantly reduces the quality of life for millions survivors worldwide, with no established treatments currently available. High slow-wave activity (SWA) sleep immediately after rodent TBI improves posttraumatic outcomes. However, pharmacological SWA-enhancing strategies are hindered by severe specificity and scalability issues that prevent it from effectively reaching clinical implementation. Alternatively, closed-loop auditory stimulation (CLAS) slow waves offers...
Prolactin, a pleiotropic hormone secreted by lactotropes, has reproductive and metabolic functions. Chronically elevated prolactin levels increase food intake, but in some hyperprolactinemic states such as the global dopamine D2 receptor (D2R) knockout mouse, intake is not increased. Here, we conduct cell-specific genetic dissection study using conditional mutant mice that selectively lack D2Rs from pituitary lactotropes (lacDrd2KO) to evaluate role of without any confounding effect central...
Competition between adult males for limited resources such as food and receptive females is shaped by the male pattern of pituitary growth hormone (GH) secretion that determines body size production urinary pheromones involved in male-to-male aggression. In brain, dopamine (DA) provides incentive salience to stimuli predict availability sexual partners. Although importance GH axis central DA neurotransmission social dominance fitness clearly appreciated, two systems have always been studied...
Traumatic brain injury (TBI) is a major cause of persistent disabilities such as sleep-wake disorders (SWD). Rodent studies SWD after TBI are scarce, however, because lack appropriate models reproducing acceleration-deceleration forces and compatible with electroencephalography/myography (EEG/EMG)-based recordings vigilance states. We therefore adapted the Marmarou impact acceleration model to allow for compatibility EEG-headset implantation. After implantation EEG/EMG electrodes, we induced...
Coma and chronic sleepiness are common after traumatic brain injury (TBI). Here, we explored whether to arousal-promoting brainstem neurons occurs in patients with fatal TBI. Postmortem examination of 8 TBI 10 controls. Compared controls, had 17% fewer serotonergic the dorsal raphe nucleus (effect size: 1.25), but number did not differ median nucleus. also 29% noradrenergic locus coeruleus 0.96). The cholinergic pedunculopontine laterodorsal tegmental nuclei (PPT/LDT) was similar injures...
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. It produces diffuse axonal (DAI), which contributes to cognitive impairment, but effective disease-modifying treatment strategies are missing. We have recently developed rat model closed skull TBI that reproduces human consequences, including DAI clinical sequelae such as memory impairment. Here, we investigated whether sleep modulation after trauma has an impact on outcome. assessed cognition with the novel...
Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development further our understanding, implementation of the method animal models is indispensable. Here, we report successful employment slow waves’ closed-loop stimulation (CLAS) rats. To validate this new tool both conceptually functionally, tested effects up- down-phase CLAS on proportions spectral characteristics sleep, learning performance...
Abstract Boosting slow-wave activity (SWA) by modulating slow-waves through closed-loop auditory stimulation (CLAS) might provide a powerful nonpharmacological tool to investigate the link between sleep and neurodegeneration. Nevertheless, CLAS in this context was not yet explored. Here, we established mouse (mCLAS)-mediated SWA enhancement explored its effects onto deficits neurodegeneration, targeting up-phase of models Alzheimer’s (AD, Tg2576) Parkinson’s disease (PD, M83). We found that...
Sleep disruption in the acute phase after stroke has detrimental effects on recovery both humans and animals. Conversely, effect of sleep promotion remains unclear. Baclofen (Bac) is a known non-rapid eye movement (NREM) sleep-promoting drug The aim this study was to investigate Bac rat model focal cerebral ischemia (isch).Rats, assigned three experimental groups (Bac/isch, saline/isch, or Bac/sham), were injected twice daily for 10 consecutive days with saline, starting 24 h induction...
Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, rate-limiting step in synthesis catecholamines. Mutations TH gene encoding tyrosine are associated with autosomal recessive disorder deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, complex encephalopathy perinatal onset, B. We generated homozygous Th knock-in mice mutation Th-p.R203H, equivalent most recurrent human B deficiency (TH-p.R233H),...
To introduce restricted DNA recombination events into catecholaminergic neurons using the Cre/loxP technology, we generated transgenic mice carrying Cre recombinase gene driven by a 9 kb rat tyrosine hydroxylase (TH) promoter. Immunohistochemistry performed on mouse brain sections revealed high number of cells expressing in areas where TH is normally expressed, including olfactory bulb, hypothalamic and midbrain dopaminergic neurons, locus coeruleus. Double immunohistochemistry...
Apathy is considered to be a core feature of Parkinson's disease (PD) and has been associated with variety states symptoms the disease, such as increased severity motor symptoms, impaired cognition, executive dysfunction, dementia. Apart from high prevalence apathy in PD, which estimated about 40%, underlying pathophysiology remains poorly understood current treatment approaches are unspecific proved only partially effective. In animal models, sub-optimally modeled, mostly by means...
Although sleep-wake disturbances are prevalent and well described after traumatic brain injury, their pathophysiology remains unclear, most likely because human injury is a highly heterogeneous entity that makes the systematic study of in relation to trauma-induced histological changes challenging task. Despite increasing interest, specific effective treatment strategies for post-traumatic still missing. With present work, therefore, we aimed at studying acute chronic by electrophysiological...