Daniel Havas

A standardized in vivo platform for preclinical screening of therapeutic interventions in rat thoracic spinal cord injury

Johana Bastidas, Linda Jones, Marco Baptista, Jason J. Wheeler et autres

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Brain Alterations Linked to the MPTP Mouse Model of Parkinson's Disease Uncovered by Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy

Ajay Modi, Sheetal Maria, Jana Kučerová, Eva Dražanová et autres

ABSTRACT Aims This study employed diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy ( 1 H‐MRS) on an MPTP‐induced mouse model of Parkinson's disease (PD) to examine microstructural changes linked to neuroinflammation and neurodegeneration. Methods MPTP (20 mg/kg, i.p.) was given …

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Locomotor, Sensorimotor and Pain Outcomes after Graded Mid-Thoracic Contusion in Female Sprague Dawley Rats

Johana Bastidas, Linda Jones, Marco Baptista, Jason Wheeler et autres

STUDY PURPOSE: The objective of this study was to develop and characterize a standardized rat thoracic contusion spinal cord injury (SCI) platform using a commercially available injury device and established methodologies. By applying a graded injury model and a comprehensive set of …

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Microgliosis and aberrant interferon response in Adar Mavs brain are rescued by PKR removal

Valentina Lacovich, Stanislav Stejskal, Kristina Locker Kovačovicova, David Potěšil et autres

Mutations in the human ADAR gene, encoding adenosine deaminase acting on RNA 1 (ADAR1), cause Aicardi-Goutières syndrome 6, which is a severe auto-inflammatory encephalopathy with aberrant interferon (IFN) induction. AdarΔ2-13 null mutant mouse embryos lacking ADAR1 protein die with high levels of …

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Target Validation Studies of PS48, a PDK-1 Allosteric Agonist, for the Treatment of Alzheimer’s Disease Phenotype in APP/PS1 Transgenic Mice

Henry W. Querfurth, Cynthia Ann Lemere, Jason Ciola, Daniel Havas et autres

The Alzheimer's disease (AD)-affected brain is known to be deficient in the utilization of glucose, its main energy substrate, and systemic diabetes is a significant risk factor for AD. In the course of biochemical and molecular investigations into this puzzling relationship, it …

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Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury

Valentina Lacovich, Mária E. Čarná, Sebastian J. Novotný, Shanshan Wang et autres

INTRODUCTION: Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI. METHODS: We assessed brain morphology (n = 4-9 mice/group), transcriptome …

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Amyloid precursor protein induces reactive astrogliosis

Gretsen Velezmoro Jáuregui, Dragana Vukić, Isaac G. Onyango, Carlos F. Arias et autres

AIM: Astrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we …

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Swedish Alzheimer’s disease variant perturbs activity of retrograde molecular motors and causes widespread derangement of axonal transport pathways

Monica Feole, Victorio M. Pozo Devoto, Neda Dragišić, Cayetana Arnaiz et autres

Experimental studies in flies, mice, and humans suggest a significant role of impaired axonal transport in the pathogenesis of Alzheimer's disease (AD). The mechanisms underlying these impairments in axonal transport, however, remain poorly understood. Here we report that the Swedish familial AD …

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Amyloid precursor protein induces reactive astrogliosis

Gretsen Velezmoro Jáuregui, Dragana Vukić, Isaac G. Onyango, Carlos F. Arias et autres

evidence demonstrating that Amyloid Precursor Protein (APP) acts as an essential instigator of reactive astrogliosis. Cell-specific overexpression of APP in cultured astrocytes led to remodelling of the intermediate filament network, enhancement of cytokine production and activation of cellular programs centred around the …

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Preclinical characterization and IND‐enabling safety studies for PNT001, an antibody that recognizes cis‐pT231 tau

Kelly Foster, Matteo Manca, Kim F. McClure, Pyry P. Koivula et autres

BACKGROUND: The cis-conformer of tau phosphorylated at threonine-231 (cis-pT231 tau) is hypothesized to contribute to tauopathies. PNT001 is a humanized, monoclonal antibody that recognizes cis-pT231 tau. PNT001 was characterized to assess clinical development readiness. METHODS: Affinity and selectivity were assessed by surface …

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Immunotherapy targeting the C-terminal domain of TDP-43 decreases neuropathology and confers neuroprotection in mouse models of ALS/FTD

Tariq Afroz, Elodie Chevalier, Mickaël Audrain, Christopher Dumayne et autres

Effective therapies are urgently needed to safely target TDP-43 pathology as it is closely associated with the onset and development of devastating diseases such as frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). In addition, TDP-43 pathology is …

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Diffusion kurtosis imaging detects brain microstructural alterations in three mouse models of Parkinson’s disease

Jana Rudá, Eva Dražanová, Alžběta Šejnoha Minsterová, Anas Arab et autres

The aim of this research is to test the ability of diffusion kurtosis imaging (DKI) to detect Parkinson´s disease-like pathology at an early stage when a neuroprotective treatment may still be effective.