Insights From TgF344-AD, a Double Transgenic Rat Model in Alzheimer’s Disease Research DOI Creative Commons
Andrew Nataraj, Karel Blahna, Karel Ježek

et al.

Physiological Research, Journal Year: 2025, Volume and Issue: 1/2025, P. 1 - 17

Published: March 10, 2025

Alzheimer's disease (AD), a leading cause of dementia worldwide, is multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tauopathy, neuronal loss, neuro-inflammation, brain atrophy, and cognitive deficits. AD manifests as familial early-onset (FAD) with specific gene mutations or sporadic late-onset (LOAD) caused various genetic environmental factors. Numerous transgenic rodent models have been developed to understand pathology development progression. The TgF344-AD rat model double that carries two human mutations: APP the Swedish mutation PSEN-1 Δ exon 9 mutations. This exhibits complete repertoire in an age-dependent manner. review summarizes multidisciplinary research insights gained from studying rats context pathology. We explore neuropathological findings; electrophysiological assessments revealing disrupted synaptic transmission, reduced spatial coding, network-level dysfunctions, altered sleep architecture; behavioral studies highlighting impaired memory; alterations excitatory-inhibitory systems; molecular physiological changes emphasizing their age-related effects. Additionally, impact interventions studied compiled, underscoring role bridging gaps understanding pathogenesis. offers significant potential identifying biomarkers for early detection therapeutic interventions, providing robust platform advancing translational research.

Language: Английский

Engineered Exosomes Improve the Effects of Curcumin on Protecting Mitochondria of Neurons in Alzheimer's Disease DOI

Yaning Ding,

Meiqi Li, Jiayi Song

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Pharmacological Targeting of the NMDAR/TRPM4 Death Signaling Complex with a TwinF Interface Inhibitor Prevents Excitotoxicity-Associated Dendritic Blebbing and Organelle Damage DOI Creative Commons
Omar A. Ramírez, Andrea Hellwig, Zihong Zhang

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 195 - 195

Published: Jan. 28, 2025

Focal swellings of dendrites (“dendritic blebbing”) together with structural damage mitochondria and the endoplasmic reticulum (ER) are morphological hallmarks glutamate neurotoxicity, also known as excitotoxicity. These pathological alterations generally thought to be caused by so-called “overactivation” N-methyl-D-aspartate receptors (NMDARs). Here, we demonstrate that activation extrasynaptic NMDARs, specifically when forming a protein–protein complex TRPM4, drives these traits. In contrast, strong synaptic NMDARs fails induce cell despite evoking plateau-type calcium signals comparable those generated NMDAR/TRPM4 complex, indicating high intracellular levels per se not toxic neurons. Using confocal laser scanning microscopy transmission electron microscopy, show disrupting using recently discovered small-molecule TwinF interface inhibitor FP802 inhibits NMDA-induced neurotoxicity-associated dendritic blebbing ER. It prevents, at least in part, disruption ER–mitochondria contact sites. findings establish trigger for organelles associated They suggest addition inducing high-amplitude, signals, generates second signal required neurotoxicity (“two-hit hypothesis”). As organelles, particularly mitochondria, is common feature many human neurodegenerative diseases, including Alzheimer’s disease amyotrophic lateral sclerosis (ALS), inhibitors have potential provide neuroprotection across broad spectrum diseases.

Language: Английский

Citations

0
Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model DOI Creative Commons
Linlin Zhang, Pei Liu, Xin Wang

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 223, P. 111280 - 111280

Published: Feb. 25, 2025

The impairment of cognitive function has been associated with Alzheimer's disease (AD). Exercise exerts a positive modulatory effect on cognition by reducing synapse injury. However, limited in vivo evidence is available to validate the neuroprotective TREM2 synaptic this phenomenon. Here, we aim explore whether physical exercise pretreatment alters Aβ-induced recognition memory structural plasticity within hippocampus AD rats. METHODS：: In study 1, fifty-two Sprague-Dawley (SD) rats were randomly divided into following four groups: control group (C group, n = 13), (AD 4 weeks and (Exe+AD blank (Exercise 13). Four treadmill intervention was performed, model established intra-cerebroventricular injection (ICV) Aβ1-42 protein. After 3 weeks, also conducted novel object test evaluate behavior assessment. Golgi staining transmission electron microscopy used morphology ultrastructure neurons. Western blotting measure expression hippocampal proteins. Extracellular neurotransmitters detected microdialysis coupled high-performance liquid chromatography. 2, 33 SD three 11), AAV-Control (AAV-Control+Exe+AD AAV-TREM2 (AAV-TREM2 +Exe+AD 11). Stereotactic intracerebral bilateral performed achieve microglial down-expression using adeno-associated virus (AAV) CD68 promoter. Aβ injection, all received molecular experiment, which same experiment 2. Novel index significantly decreased, western blot demonstrate that protein decreased (P < 0.001). But reversed phenomenon(P addition, compared Con neuron from Exe+AD exhibited more complex branching pattern 0.05). And impaired observed group. Hippocampal synaptic-related (SYX, SYP, GAP43, PSD95) neurotransmitter (DA, Glu, GABA) 0.01) neuroprotection can be found are inhibition injury activate when blockade reduced brain protective rat model, including increased damage neuronal dendritic complexity, ultrastructure, decrease synapses-related protein, typical neurotransmitter. Treadmill facilitated acquisition via TREM2-mediated an model.

Language: Английский

Citations

0
Phenylpropanoids of Eleutherococcus senticosus (Rupr. & maxim.) maxim. Alleviate oxidative stress in Alzheimer's disease in vitro and in vivo models by regulating Mst1 and affecting the Nrf2/Sirt3 pathway DOI
Rui Yang, Xin Meng, Wei Zhao

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 159, P. 108347 - 108347

Published: March 8, 2025

Language: Английский

Citations

0
Insights From TgF344-AD, a Double Transgenic Rat Model in Alzheimer’s Disease Research DOI Creative Commons
Andrew Nataraj, Karel Blahna, Karel Ježek

et al.

Physiological Research, Journal Year: 2025, Volume and Issue: 1/2025, P. 1 - 17

Published: March 10, 2025

Alzheimer's disease (AD), a leading cause of dementia worldwide, is multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tauopathy, neuronal loss, neuro-inflammation, brain atrophy, and cognitive deficits. AD manifests as familial early-onset (FAD) with specific gene mutations or sporadic late-onset (LOAD) caused various genetic environmental factors. Numerous transgenic rodent models have been developed to understand pathology development progression. The TgF344-AD rat model double that carries two human mutations: APP the Swedish mutation PSEN-1 Δ exon 9 mutations. This exhibits complete repertoire in an age-dependent manner. review summarizes multidisciplinary research insights gained from studying rats context pathology. We explore neuropathological findings; electrophysiological assessments revealing disrupted synaptic transmission, reduced spatial coding, network-level dysfunctions, altered sleep architecture; behavioral studies highlighting impaired memory; alterations excitatory-inhibitory systems; molecular physiological changes emphasizing their age-related effects. Additionally, impact interventions studied compiled, underscoring role bridging gaps understanding pathogenesis. offers significant potential identifying biomarkers for early detection therapeutic interventions, providing robust platform advancing translational research.

Language: Английский

Citations

0