Motor deficits and brain pathology in the Parkinson's disease mouse model hA53Ttg.

Background: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of α-synuclein (α-syn) aggregates. The A53T missense point mutation occurs in autosomal dominant familial PD and has been found to promote the aggregation of α-syn. To investigate the role of the A53T mutation in PD, researchers have developed various mouse models with this mutation.

Effect of astaxanthin in type-2 diabetes -induced APPxhQC transgenic and NTG mice.

Objectives: Aggregation and misfolding of amyloid beta (Aβ) and tau proteins, suggested to arise from post-translational modification processes, are thought to be the main cause of Alzheimer's disease (AD). Additionally, a plethora of evidence exists that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), and dyslipidemia to the pathogenesis of AD. We thus investigated the combinatory effect of T2D and human glutaminyl cyclase activity (pyroglutamylation), on the pathology of AD and whether astaxanthin (ASX) treatment ameliorates accompanying pathophysiological manifestations.

Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and -KO mouse models.

Introduction: Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by two core behavioral symptoms: impaired social communication and interaction, as well as stereotypic, repetitive behavior. No distinct cause of ASD is known so far; however, excitatory/inhibitory imbalance and a disturbed serotoninergic transmission have been identified as prominent candidates responsible for ASD etiology.

Methods: The GABA receptor agonist R-Baclofen and the selective agonist for the 5HT serotonin receptor LP-211 have been reported to correct social deficits and repetitive behaviors in mouse models of ASD.

Leukotriene Signaling as a Target in α-Synucleinopathies.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are two common types of α-synucleinopathies and represent a high unmet medical need. Despite diverging clinical manifestations, both neurodegenerative diseases share several facets of their complex pathophysiology. Apart from α-synuclein aggregation, an impairment of mitochondrial functions, defective protein clearance systems and excessive inflammatory responses are consistently observed in the brains of PD as well as DLB patients.

Characterization of an APP/tau rat model of Alzheimer's disease by positron emission tomography and immunofluorescent labeling.

Background: To better understand the etiology and pathomechanisms of Alzheimer's disease, several transgenic animal models that overexpress human tau or human amyloid-beta (Aβ) have been developed. In the present study, we generated a novel transgenic rat model by cross-breeding amyloid precursor protein (APP) rats with tau rats. We characterized this model by performing positron emission tomography scans combined with immunofluorescent labeling and cerebrospinal fluid analyses.

Evaluation of Neuropathological Features in the SOD1-G93A Low Copy Number Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) still depicts an incurable and devastating disease. Drug development efforts are mostly based on superoxide dismutase 1 gene (SOD1)-G93A mice that present a very strong and early phenotype, allowing only a short time window for intervention. An alternative mouse model is available, that is based on the same founder line but has a reduced SOD1-G93A copy number, resulting in a weaker and delayed phenotype.

Homozygosity of BACHD rats not only causes strong behavioral deficits in young female rats but also a reduced breeding success.

Huntington's disease is known to be a purely genetic disease based on an expansion of a CAG base triplet repeat in the coding region of the Huntingtin gene. Some years ago, researchers were able to introduce the extensive full-length gene sequence of the mutant huntingtin gene into a rodent model. The resulting BACHD rat is already well characterized for behavioral deficits.

Metabolic, Phenotypic, and Neuropathological Characterization of the Tg4-42 Mouse Model for Alzheimer's Disease.

Background: Preclinical Alzheimer's disease (AD) research strongly depends on transgenic mouse models that display major symptoms of the disease. Although several AD mouse models have been developed representing relevant pathologies, only a fraction of available mouse models, like the Tg4-42 mouse model, display hippocampal atrophy caused by the death of neurons as the key feature of AD. The Tg4-42 mouse model is therefore very valuable for use in preclinical research.

Quantification of Huntington's Disease Related Markers in the R6/2 Mouse Model.

Huntington's disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result in a devasting and lethal phenotype. Neurodegeneration in HD begins in the striatum and spreads to other brain regions such as cortex and hippocampus, causing motor and cognitive dysfunctions. To understand the signaling pathways involved in HD, animal models that mimic the human pathology are used.

Constant Levels of Tau Phosphorylation in the Brain of htau Mice.

Excessive tau phosphorylation is the hallmark of tauopathies. Today's research thus focusses on the development of drugs targeting this pathological feature. To test new drugs in preclinical studies, animal models are needed that properly mimic this pathological hallmark.

Correlation of pyroglutamate amyloid β and ptau Ser202/Thr205 levels in Alzheimer's disease and related murine models.

Senile plaques frequently contain Aβ-pE(3), a N-terminally truncated Aβ species that is more closely linked to AD compared to other Aβ species. Tau protein is highly phosphorylated at several residues in AD, and specifically phosphorylation at Ser202/Thr205 is known to be increased in AD. Several studies suggest that formation of plaques and tau phosphorylation might be linked to each other.

Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value.

Neurofilament-light chain (NF-L) is a well-known clinical biomarker of many neurodegenerative diseases. By analyzing amyotrophic lateral sclerosis (ALS) patients cerebrospinal fluid (CSF) or plasma, progression of NF-L levels can forecast conversion from the presymptomatic to symptomatic stage and time of survival. The use of plasma for NF-L measurement makes this biomarker exceptionally valuable for clinical studies since sample collection can be performed repeatedly without causing much harm.

Validation of behavioral phenotypes in the BACHD rat model.

Huntington disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion in the HTT gene. Various HD animal models have been generated to mimic the motor, cognitive and neuropsychiatric disturbances that affect HD patients. Reproducing disease phenotypes within these models is essential to identify reliable readouts for therapy studies.

Transgene integration causes RARB downregulation in homozygous Tg4-42 mice.

Alzheimer's disease can be modelled by different transgenic mouse strains. To gain deeper insight into disease model mechanisms, the previously described Tg4-42 mouse was analysed for transgene integration. On RNA/DNA level the transgene integration resulted in more than 20 copy numbers and further caused a deletion of exon 2 of the retinoic acid receptor beta.

Plasma pharmacokinetic and metabolism of [F]THK-5317 are dependent on sex.

Introduction: Tau deposition is one of the hallmarks of Alzheimer's disease (AD) and can be visualized and quantified using [F]THK-5317 together with kinetic modeling. To determine the feasibility of this approach, we measured blood/plasma pharmacokinetics and radiotracer metabolism in female and male rats.

Methods: Female and male rats (n = 11-12) were cannulated via the femoral artery for continuous blood sampling.

Characterization of the visceral and neuronal phenotype of 4L/PS-NA mice modeling Gaucher disease.

Gaucher disease is caused by a deficiency in glucocerebrosidase that can result in non-neuronal as well as neuronal symptoms. Common visceral symptoms are an increased organ size, specifically of the spleen, and glucosylceramide as well as glucosylsphingosine substrate accumulations as a direct result of the glucocerebrosidase deficiency. Neuronal symptoms include motor deficits and strong alterations in the cerebellum.

Hepatic and neuronal phenotype of NPC1 mice.

Niemann-Pick type C disease (NPC) is a fatal autosomal recessive disorder characterized by a defect in the intracellular transport of lipoproteins leading to the accumulation of lipids in diverse tissues. A visceral and neuronal phenotype mimicking human NPC1 disease has been described in NPC1 mutant mice. These mice are by now the most widely used NPC1 rodent model to study NPC and developmental compounds against this devastating disease.

Correction: Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease.

[This corrects the article DOI: 10.1371/journal.pone.

Phosphorylation of different tau sites during progression of Alzheimer's disease.

Alzheimer's disease is characterized by accumulation of amyloid plaques and tau aggregates in several cortical brain regions. Tau phosphorylation causes formation of neurofibrillary tangles and neuropil threads. Phosphorylation at tau Ser202/Thr205 is well characterized since labeling of this site is used to assign Braak stage based on occurrence of neurofibrillary tangles.

mTh1 driven expression of hTDP-43 results in typical ALS/FTLD neuropathological symptoms.

Transgenic mouse models are indispensable tools to mimic human diseases and analyze the effectiveness of related new drugs. For a long time amyotrophic lateral sclerosis (ALS) research depended on only a few mouse models that exhibit a very strong and early phenotype, e.g.

Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease.

Huntington disease is an inherited neurodegenerative disorder characterized by motor, cognitive, psychiatric and metabolic symptoms. We recently published a study describing that the BACHD rat model of HD shows an obesity phenotype, which might affect their motivation to perform food-based behavioral tests. Further, we argued that using a food restriction protocol based on matching BACHD and wild type rats' food consumption rates might resolve these motivational differences.