A M1 muscarinic acetylcholine receptor-specific positive allosteric modulator VU0486846 reduces neurogliosis in female Alzheimer's mice.

Alzheimer's disease (AD) is the most prevalent type of dementia, disproportionately affecting females, who make up nearly 60% of diagnosed cases. In AD patients, the accumulation of beta-amyloid (Aβ) in the brain triggers a neuroinflammatory response driven by neuroglia, worsening the condition. We have previously demonstrated that VU0486846, an orally available positive allosteric modulator (PAM) targeting M1 muscarinic acetylcholine receptors, enhances cognitive function and reduces Aβ pathology in female APPswe/PSEN1ΔE9 (APP/PS1) mice.

Comparison of Huntington's disease phenotype progression in male and female heterozygous FDNQ175 mice.

Huntington's Disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment due to the expansion of a polyglutamine (CAG) repeat in the N-terminal region of the huntingtin (Htt) protein. The creation of HD mouse models represents a critical step in the research for HD treatment. Among the currently available HD mouse models, the zQ175 knock-in mouse line is the first to display robust disease phenotype on a heterozygous background.

Metabotropic Glutamate Receptor 5 Antagonism Reduces Pathology and Differentially Improves Symptoms in Male and Female Heterozygous zQ175 Huntington's Mice.

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment. There are currently no available disease modifying treatments for HD patients. We have previously shown that pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) signaling rescues motor deficits, improves cognitive impairments and mitigates HD neuropathology in male zQ175 HD mice.

A positive allosteric modulator for the muscarinic receptor (M1 mAChR) improves pathology and cognitive deficits in female APPswe/PSEN1ΔE9 mice.

Background And Purpose: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, and women account for 60% of diagnosed cases. β-Amyloid (Aβ) oligomers are considered the principal neurotoxic species in AD brains. The M1 muscarinic ACh receptor (M1 mAChR) plays a key role in memory and learning.

Metabotropic Glutamate Receptor 2/3 Activation Improves Motor Performance and Reduces Pathology in Heterozygous zQ175 Huntington Disease Mice.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that leads to progressive motor impairments with no available disease-modifying treatment. Current evidence indicates that exacerbated postsynaptic glutamate signaling in the striatum plays a key role in the pathophysiology of HD. However, it remains unclear whether reducing glutamate release can be an effective approach to slow the progression of HD.

Bioaccumulation and physiological responses of the turtle Chelydra serpentina exposed to polychlorinated biphenyls during early life stages.

Despite the North American production ban of polychlorinated biphenyls (PCBs), PCBs are ubiquitous in the environment and in wildlife tissues. Chelydra serpentina serpentina (common snapping turtle) have been used as environmental indicators of PCB pollution upwards of 40 years given their high site fidelity and high trophic position. Despite their long use as indicators of PCB contamination, the effects of PCBs in reptiles remain largely unknown.

N-phenyl-1-naphthylamine (PNA) Accumulates in Snapping Turtle (Chelydra serpentina) Liver Activating the Detoxification Pathway.

Substituted phenylamine antioxidants (SPAs) are used in Canadian industrial processes. SPAs, specifically N-phenyl-1-naphthylamine (PNA), have received very little attention despite their current use in Canada and their expected aquatic and environmental releases. There is a research gap regarding the effects of PNA in wildlife; therefore, Chelydra serpentina (common snapping turtle) was studied due to its importance as an environmental indicator species.

Food-Borne Exposure of Juvenile Rainbow Trout (Oncorhynchus mykiss) to Benzotriazole Ultraviolet Stabilizers Alone and in Mixture Induces Specific Transcriptional Changes.

Benzotriazole ultraviolet-stabilizers (BZT-UVs) are commonly used as additives to protect from light-induced degradation in a variety of consumer goods. Despite their widespread presence in aquatic ecosystems, information on the effects of these compounds remains largely unknown. The objectives of the present study were to evaluate the chronic effects of 2 BZT-UVs alone and in a mixture, 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol (UV-234) and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV-328), in juvenile rainbow trout (Oncorhynchus mykiss) chronically exposed (for 28 d) through the diet.

Cumulative effects of municipal effluent and parasite infection in yellow perch: A field study using high-throughput RNA-sequencing.

Multiple metabolic, immune and reproductive effects have been reported in fish residing in effluent-impacted sites. Natural stressors such as parasites also have been shown to impact the responses of organisms to chronic exposure to municipal effluent in the St. Lawrence River (Quebec, Canada).

Biomarkers of exposure to nanosilver and silver accumulation in yellow perch (Perca flavescens).

There is a risk of exposure of aquatic organisms to silver nanoparticles (AgNPs) from discharges of municipal and industrial wastewater. In the present study, yellow perch (Perca flavescens) were exposed to environmentally relevant concentrations (1 mg/L and 100 mg/L) of AgNPs and silver ions (Ag ) in static-renewal experiments conducted over 96 h and 10 d. The greatest accumulation of total Ag occurred in the liver of P.