Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 12, 2025

Background Animal models of Alzheimer’s disease (AD) are essential tools for investigating pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal glial alterations in the hippocampus medial prefrontal cortex (mPFC) young TgF344-AD rats correlated these changes with cognitive decline amyloid-β plaque load. Methods We compared non-transgenic littermate aged 7–8 months age. systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, somatostatin-positive neurons), newly generated neurons hippocampus. Spatial learning memory were assessed using Barnes maze test. Results Young had a large number amyloid plaques both mPFC, together pronounced increase microglial cell numbers. Astrocytic activation was significant mPFC. Cholecystokinin-positive numbers decreased transgenic rats, but calretinin-, not altered. Adult neurogenesis affected by genotype. spatial impairments, deficit did correlate or cellular brain. hippocampus, negatively cholecystokinin-positive neuron astrocytes. Conclusion Pronounced neuropathological found mPFC including loss hippocampal interneurons. Some load, impairment.

Language: Английский

---

Rats Lacking the Dopamine Transporter Display Inflexibility in Innate and Learned Behavior

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1270 - 1270

Published: June 7, 2024

Playing a key role in the organization of striatal motor output, dopamine (DA)-ergic system regulates both innate and complex learned behaviors. Growing evidence clearly indicates involvement DA-ergic different forms repetitive (perseverative) behavior. Some these behaviors accompany such disorders as obsessive-compulsive disorder (OCD), Tourette's syndrome, schizophrenia, addiction. In this study, we have traced how inflexibility reactions recently developed animal model hyper-DA-ergia, transporter knockout rats (DAT-KO rats), affects realization behavior (grooming) learning spatial (learning reversal T-maze) non-spatial (extinction operant reaction) tasks. We found that microstructure grooming DAT-KO significantly differed comparison to control rats. more often demonstrated fixed syntactic chain, making fewer errors very rarely missing chain steps rats' during inter-grooming intervals was completely animals. During T-maze, displayed pronounced patterns hyperactivity perseverative (stereotypical) activity, which led worse performance task. Most could not properly learn behavioral task question. re-learning, rigid activity even absence any reinforcement. tasks, mutant poor extinction lever pressing: they continued perform presses despite no there being Our results suggest abnormally elevated DA levels may be responsible for rigidity. It is conceivable phenomenon reflects some traits observed clinical conditions associated with endogenous or exogenous substance abuse, OCD, patients Parkinson disease treated mimetics, etc. Thus, valuable search new pharmacological approaches treat illnesses.

Language: Английский

---

Toxoplasmosis accelerates the progression of hereditary spastic paraplegia

mSphere, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

ABSTRACT The parasitic protozoa Toxoplasma gondii chronically infects the central nervous system of an estimated one-third human population. Infection is generally subclinical, but immunocompromised individuals can experience a variety neurological symptoms. Meta-analyses T. seropositivity have suggested correlation between infection and neurologic disease. Although mechanistic studies on relationship disease been attempted in mice, they are particularly susceptible to , making them effective model for investigating mechanisms infection, not ideal examining long-term chronic Rats more closely mimic cyst levels after acute lack rat models has limited interplay progression. We employed previously characterized complex form hereditary spastic paraplegia (HSP), class neurodegenerative disorders that cause axonal degeneration lower limb spasticity, order assess effect find infected rats with exhibit significantly exacerbated behavioral neuromorphological HSP symptoms compared uninfected mutant rats, little correlative versus control animals. further all regardless genotype, robust immune response presenting parasite below limit detection multiple assays parasitemia exhibiting no detectable increase neuroinflammation 7 weeks post-infection. These results suggest undetected may exacerbate even immunocompetent contribute heterogeneity. IMPORTANCE consequences previous infections poorly understood becoming increasingly appreciated, era long COVID. Altered progression other diseases later life be among infections. Here, we investigate which ~30% global population, using (HSP). accelerate motor dysfunction despite clearance by rats. Our cleared alter

Language: Английский

---

Toxoplasma gondii infection accelerates the progression of hereditary spastic paraplegia

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 15, 2024

Abstract The parasitic protozoa Toxoplasma gondii chronically infects the central nervous system of an estimated one-third human population. Infection is generally subclinical, but immunocompromised individuals can experience a variety neurological symptoms. Meta-analyses T. seropositivity have suggested correlation between infection and neurologic disease. While mechanistic studies on relationship disease been attempted in mice, mice are particularly susceptible to , making them effective model for investigating mechanisms infection, not ideal examining long-term chronic Rats more closely mimic clearance after acute lack rat models has limited interplay progression. We employed previously characterized complex form hereditary spastic paraplegia (HSP), class neurodegenerative disorders which cause axonal degeneration lower limb spasticity, order assess effect find that infected rats with exhibit significantly exacerbated behavioral neuromorphological HSP symptoms compared uninfected mutant rats, little correlative versus control animals. further all regardless genotype robust immune response effectively clearing parasite below limit detection multiple assays parasitemia exhibiting no detectable increase neuroinflammation seven weeks post-infection. These results suggest undetected may exacerbate even immunocompetent contribute heterogeneity. Author Summary consequences previous infections poorly understood, becoming increasingly appreciated, era long Covid. Altered progression other diseases later life be among infections. Here we investigate ∼30% global population, using (HSP). accelerates motor dysfunction despite by rats. Our cleared alter

Language: Английский

---

Animal models for research on neurodegenerative diseases

Ageing and Neurodegenerative Diseases, Journal Year: 2023, Volume and Issue: 3(3)

Published: Aug. 28, 2023

Language: Английский

---

Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17213 - 17213

Published: Dec. 7, 2023

In this article, we briefly describe human neurodegenerative diseases (NDs) and the experimental models used to study them. The main focus is yeast Saccharomyces cerevisiae as an model processes. We review recent data on aggregation of disease-related proteins in cells. addition, results studies that were designed investigate molecular mechanisms underlie reporter proteins. advantages disadvantages approaches are currently formation protein aggregates described. Special attention given similarity between form a result misfolding viral factories-special structural formations which particles formed inside virus-infected A separate part devoted our previously published upon expression insect densovirus capsid Based reviewed NDs related aggregation, well new system for proposed. core proposed comparative transcriptomic analysis changes signaling pathways during

Language: Английский

---