Modelling human brain-wide pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits
By savannah onIn parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model may open new research avenues in the field of brain aging and neurodegeneration.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
By savannah onThe authors increased Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders. View original preprint.
Is Gauchian genotyping of GBA1 variants reliable?
By Emma Sherrell onPreprint: The authors evaluated Gauchian in 90 Sanger-sequenced patients with GD and five GBA1 heterozygotes using the software tool Gauchian to identify GBA1 variants from whole genome sequencing. While Gauchian genotyped most patients correctly, this limits Gauchian's utility in variant screening and precluding its use in diagnostics.
Population fraction of Parkinson’s disease attributable to preventable risk factors
By Emma Sherrell onPublished: The team identified repeated blows to head in sports/combat as a potential new risk factor. 23% of PD cases in females were attributable to pesticides/herbicides exposure, and 30% of PD in males were attributable to pesticides/herbicides, military-related chemical exposures, and repeated blows to the head, and therefore could have potentially been prevented. View original preprint.
PyRates—A code-generation tool for modeling dynamical systems in biology and beyond
By Emma Sherrell onPublished: The main purpose of the paper is to demonstrate how these three tools can support the computational/mathematical modeling of neural systems with a variety of numerical methods that are well tested and documented. Thus, the authors present a powerful tool kit for computational/mathematical approaches to studying the dynamics and functions of complex neural systems such as the basal ganglia. View original preprint.
RASP: Optimal single fluorescent puncta detection in complex cellular backgrounds
By savannah onPublished: This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments with a sensitivity down to the level of the single protein. View original preprint.
Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson’s disease
By Emma Sherrell onPublished: To understand PD-associated sleep-wake abnormalities, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. View original preprint.
Rethinking the network determinants of motor disability in Parkinson’s disease
By Emma Sherrell onWhile the basal ganglia circuit model underpinning the notion that striatal dopamine (DA) depletion was the critical determinant of network pathophysiology underlying the motor symptoms of Parkinson’s disease, the hypothesis itself has never been directly tested. It is time for a new model of the network determinants of motor disability in PD.
α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson’s disease
By Emma Sherrell onThe mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. Genetic and physiological methods were used to monitor mitochondrial function in substantia nigra pars compacta (SNc) dopaminergic and pedunculopontine nucleus (PPN) cholinergic neurons after stereotaxic injection of aSYN pre-formed fibrils (PFFs) into the mouse brain.
Dynamic behaviour restructuring mediates dopamine-dependent credit assignment
By Emma Sherrell onPublished: Reinforcement mechanism promotes not only reinforcement, but gradual refinement of the entire behavioral repertoire to assign credit to specific actions and action sequences that lead to dopamine release.
Scalable, flexible carbon fiber electrode thread arrays for three-dimensional probing of neurochemical activity in deep brain structures of rodents
By Emma Sherrell onThe authors' CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinson’s disease and major mood disorders.
Synchronous measurements of extracellular action potentials and neurochemical activity with carbon fiber electrodes in nonhuman primates
By Emma Sherrell onPublished: Synchronous measures of spike and dopamine signals displayed contrasting relations to the behavioral task parameters, as taken from the small set of representative data, suggesting a complex relationship between these two modes of neural signaling. View original preprint.
Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19
By Emma Sherrell onPublished: The team concluded from their autopsy series that after a fatal course of COVID-19, microscopic changes, when present, in the rostral, intracranial portion of the olfactory circuitry generally reflected neurodegenerative processes seen elsewhere in the brain. In general, inflammation correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19+ patients. View original preprint.
Persistent hyposmia as surrogate for α-Synuclein-Linked brain pathology
By Emma Sherrell onPreprint: The team identified significant age- and posit that simple-to-administer, quantitative smell tests could serve as inexpensive screening tools in future population studies for the identification of α-synuclein-related brain disorders, including Parkinson's during its premotor phase.
Response to: “Is Gauchian genotyping of GBA1 variants reliable?”
By Emma Sherrell onPreprint: To understand the cause of these discrepancies, the team reviewed their data, and concluded that they are misinterpreting Gauchian results in 8 of the 11 discrepant samples, and incorrectly using Gauchian to analyze low-coverage 1kGP samples.
Microbial amyloids in neurodegenerative amyloid diseases
By Emma Sherrell onPublished: Inhibiting microbial amyloids or their interactions with the host, may therefore represent a tangible target to limit various amyloid pathologies.
Anionic nanoplastic contaminants promote Parkinson’s disease–associated α-synuclein aggregation
By Emma Sherrell onThese results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson’s disease and related dementias.
A leaky gut dysregulates gene networks in the brain associated with immune activation, oxidative stress, and myelination in a mouse model of colitis
By Emma Sherrell onPreprint: The team provides a comprehensive evaluation of multiple systems in a prevalent experimental model of intestinal permeability, which will inform future studies using this model and others, assist in the identification of druggable targets in the gut-brain axis, and contribute to our understanding of the concomitance of intestinal and neuropsychiatric dysfunction.
The R1441C-LRRK2 mutation induces myeloid immune cell exhaustion in an age- and sex-dependent manner
By Emma Sherrell onPreprint: LRRK2 has become an appealing target in PD, but findings suggest that more research is required to understand the cell-type-specific consequences and optimal timing of LRRK2-targeting therapeutics.
Calcium influx into astrocytes plays a pivotal role in inflammation-driven behaviors
By Emma Sherrell onGraphical abstract.