Topic: 5xFAD mice

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by deficits in episodic memory processing and spatial navigation. Especially, the egocentric neural representation of space, which is important for constructing an egocentric cognitive map, is essential for spatial navigation. However, how spatial navigation deficits relate to egocentric neural representation of space remains unclear. The retrosplenial cortex (RSC) is one of the regions affected by amyloidosis in the early stages of AD and is well known for its role in egocentric spatial representation. Specifically, it cont

Alzheimer's disease (AD) is a progressive neurological disorder characterized by amyloid accumulation and behavioral changes across preclinical and clinical stages. Although AD is currently incurable, emerging machine-learning (ML) approaches are facilitating novel insights into disease etiology and treatment mechanisms. Our study utilized and built upon two open-source ML platforms, DeepLabCut (Mathis et al. 2018) and Variational Animal Motion Encoding (VAME) (Luxem et al. 2022), to track and analyze naturalistic behavior in App knock-in (KI) and 5xFAD transgenic mouse models of AD. New human

Immunotherapy of Alzheimer’s disease (AD) is a promising approach to reduce the accumulation of amyloid-beta (Aβ) peptides, a critical event in the onset of the disease. Emerging evidence indicate that metabotropic glutamate receptors (mGluRs) are involved in the progression of AD, representing potential targets for new treatments. Studies have highlighted the potential role of group II mGluRs, mGluR2 and mGluR3, in the modulation of Aβ production, although their respective contribution remains unclear, due to the lack of specific tools to study them. Here, we showed in vitro that enhancing mG

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common type of dementia worldwide. Pathological factors, such as Aβ deposition and glial cell activation, have been shown to be associated with changes of the glymphatic system, the drainage system of the brain parenchyma. However, the potential roles of astrocyte activity in the early stage of AD remain unclear. In this study, we aimed to investigate the changes in astrocyte activity and its pathological roles in the medial prefrontal cortex (mPFC) of 5xFAD mice at 4-5 months of age with two-photon microscopy, ch

A hallmark of Alzheimer’s disease (AD) pathology is amyloid plaques which can lead to neuroinflammation, cellular dysfunctions as well as altered neuronal activity. Both AD patients and mouse models exhibit abnormal neural oscillations, including altered gamma oscillations, hippocampal sharp wave-ripples (SWRs) and cortical sleep spindles. Although these oscillations play a role in memory formation and consolidation, it remains poorly understood how abnormal oscillations relate to novel experiences. Here we show that deficits in SWRs are experience-dependent in an AD mouse model. We performed

The increased accumulation of amyloid b (Ab) in retinal blood vessels in Alzheimer’s disease (AD) patients and AD animal models is in significant correlation with the brain amyloid deposits associated with the cognitive impairment in AD. Ab accumulation in blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD. The supplementation with high-dose fish oil (FO) have shown significant effects in diminishing AD pathologies but also serving as the blood vessel fortifier. We analyzed the changes in expression of major facilitator superfamily

Our aim is to investigate the effect of choline, fish oil, and uridine-5'-monophosphate (UMP) supplementation on lipid profiles in the 5XFAD mouse model of Alzheimer's disease (AD) was to characterize cholesterol, glycerophospholipids (GPLs), sphingolipids (SLs), glycolipids (GLs), lysophospholipids (lyso GPLs) and lysophospholipid acyltransferases (lyso GPL O-ATs), and glycerophospholipid (GPL Os).Lipidomic analysis was performed on hippocampal brain tissue samples from 3-, 6- and 9-month-old 5XFAD mice and littermate controls using cutting-edge mass spectrometers with direct infusion (shotgu

Alzheimer's disease (AD) is a complex and multi-factorial disorder, leading to progressive cognitive impairment. Hippocampal dysfunction plays a crucial role in spatial memory deficits in AD. However, the precise alterations in hippocampal neuronal activity in AD during memory-guided behaviour remain unclear. To study this, we introduced a novel behavioural paradigm for assessing spatial memory in head-fixed mice during a continuous alternation task, which can be used in conjunction with two-photon calcium imaging to investigate changes in hippocampal network activity, including spatial and tr

Strategy updating is one of the recent roles assigned to the retrosplenial cortex (RSC). Studies have shown that lesions or inactivation of RSC cause impairment in exploring and learning new alternative options when previous ones were available but no longer appropriate, suggesting its importance for set-shifting behaviors1. Building on previous evidence of impaired reversal learning in 6-month-old 5xFAD mice2, this study focuses on uncovering the synaptic correlates of reversal learning in the RSC in the context of AD. Therefore, we use a set-shifting task that challenges the animals to devel

Background: Ginseng is a representative functional food for brain health. However, its active ingredient is not well defined. Gintonin is a novel material isolated from white/red ginseng and its lysophosphatidic acid (LPA) plays as an exogenous G protein-coupled LPA receptor (LPAR) agonist. Korean red ginseng marc (KRGM) is a by-product after KRG extractions. Purpose: In previous study, we demonstrated that KRGM-derived gintonin (KRGM-G) contains LPA C18:2, which is a major functional component, as much as white and/or red ginseng has. Methods: In present study, we further studied KRGM-G-media

Despite extensive research, effective treatment for Alzheimer’s disease (AD) remains elusive. Emerging evidence suggests that the endocannabinoid system and glutamatergic neurotransmission play important roles in AD pathophysiology. This project aims to elucidate the involvement of cannabinoid type 1 receptor (CB1R) on regulating the cytotoxic effects induced by N-methyl-D-aspartate receptors (NMDARs) in AD. On the one hand, CB1R activation reduces neuroinflammation and promotes neuroprotection in AD models. On the other hand, the synaptic receptor NR2A contribute to synaptic integrity and mem

To understand how amyloidosis in Alzheimer’s Disease changes circuit properties affecting memory encoding and recall, we examined the relationship between neuronal activity, nearness to amyloid plaques, and spatial memory readout from hippocampal CA1 place cells. We performed two-photon calcium imaging in head-fixed 5xFAD mice navigating an air-lifted circular track. Neuronal hyperactivity in CA1 during non-running periods was higher in 5xFAD mice compared to wildtype littermates in both young (2-3 months) and old (6.5-10 months) groups. Moreover, neurons close to amyloid plaques (<20µm in

Alzheimer's disease (AD) is characterized by a dramatic loss of old consolidated memory. Our study proposes a new hypothesis that neurodegeneration affects mechanisms of memory reconsolidation, leading to the weakening of old memories when they are retrieved in the diseased brain, resulting in gradual self-degradation of the consolidated memory. Testing this hypothesis in transgenic 5xFAD mice we found that their contextual memory was impaired following retrieval compared to control animals. To protect memory during reconsolidation, we administered the NMDA receptor antagonist MK-801 which is