scholarly journals Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer’s Disease Mouse Model

2019 ◽  
Author(s):  
Emily A. Jones ◽  
Anna K. Gillespie ◽  
Seo Yeon Yoon ◽  
Loren M. Frank ◽  
Yadong Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Genetic Risk ◽  
Memory Impairment ◽  
Memory Loss ◽  
Memory Deficits ◽  
Power Reduction ◽  
Memory Impairments ◽  
Sharp Wave

SUMMARYAlzheimer’s disease (AD) is characterized by progressive memory loss, and there is a pressing need to identify early pathophysiological alterations that predict subsequent memory impairment. Hippocampal sharp-wave ripples (SWRs) – electrophysiological signatures of memory reactivation in the hippocampus – are a compelling candidate for doing so. Mouse models of AD show reductions in both SWR abundance and associated slow gamma (SG) power during aging, but these alterations have yet to be directly linked to memory impairments. In aged apolipoprotein E4 knock in (apoE4-KI) mice – a model of the major genetic risk factor for AD – we found that reduced SWR abundance and associated CA3 SG power predicted spatial memory impairments measured 1–2 months later. Importantly, SWR-associated CA3 SG power reduction in young apoE4-KI mice also predicted spatial memory deficits measured 10 months later. These results establish features of SWRs as potential functional biomarkers of memory impairment in AD.

Ameliorative effect of sansoninto on sleep disturbance and spatial memory impairment in an Alzheimer's disease rat model

2017 ◽  
Vol 4 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Hiroshi Moriyama ◽  
Takuya Watanabe ◽  
Kotaro Takasaki ◽  
Masaki Nagao ◽  
Kaori Kubota ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Sleep Disturbance ◽  
Rat Model ◽  
Memory Impairment ◽  
Ameliorative Effect

scholarly journals Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer’s Disease Mouse Model

Cell Reports ◽  
2019 ◽  
Vol 29 (8) ◽  
pp. 2123-2133.e4 ◽  
Author(s):  
Emily A. Jones ◽  
Anna K. Gillespie ◽  
Seo Yeon Yoon ◽  
Loren M. Frank ◽  
Yadong Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Learning And Memory ◽  
Memory Impairments ◽  
Sharp Wave

scholarly journals Noncanonical function of an autophagy protein prevents spontaneous Alzheimer’s disease

2020 ◽  
Vol 6 (33) ◽  
pp. eabb9036
Author(s):  
Bradlee L. Heckmann ◽  
Brett J. W. Teubner ◽  
Emilio Boada-Romero ◽  
Bart Tummers ◽  
Clifford Guy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Disease ◽  
Memory Impairment ◽  
Memory Loss ◽  
Tau Hyperphosphorylation ◽  
Primary Microglia ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Old Mice

Noncanonical functions of autophagy proteins have been implicated in neurodegenerative conditions, including Alzheimer’s disease (AD). The WD domain of the autophagy protein Atg16L is dispensable for canonical autophagy but required for its noncanonical functions. Two-year-old mice lacking this domain presented with robust β-amyloid (Aβ) pathology, tau hyperphosphorylation, reactive microgliosis, pervasive neurodegeneration, and severe behavioral and memory deficiencies, consistent with human disease. Mechanistically, we found this WD domain was required for the recycling of Aβ receptors in primary microglia. Pharmacologic suppression of neuroinflammation reversed established memory impairment and markers of disease pathology in this novel AD model. Therefore, loss of the Atg16L WD domain drives spontaneous AD in mice, and inhibition of neuroinflammation is a potential therapeutic approach for treating neurodegeneration and memory loss. A decline in expression of ATG16L in the brains of human patients with AD suggests the possibility that a similar mechanism may contribute in human disease.

scholarly journals N-Acetylcysteine Prevents the Spatial Memory Deficits and the Redox-Dependent RyR2 Decrease Displayed by an Alzheimer’s Disease Rat Model

2018 ◽  
Vol 10 ◽  
Author(s):  
Jamileth More ◽  
Nadia Galusso ◽  
Pablo Veloso ◽  
Luis Montecinos ◽  
José Pablo Finkelstein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Rat Model ◽  
Memory Deficits

scholarly journals Effects of Cyperus rotundus Extract on Spatial Memory Impairment and Neuronal Differentiation in Rat Model of Alzheimer's Disease

2020 ◽  
Vol 9 (1) ◽  
pp. 17
Author(s):  
Ebrahim Esfandiari ◽  
Zeinab Shakerin ◽  
Shahnaz Razavi ◽  
Hojjatallah Alaei ◽  
Mustafa Ghanadian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Neuronal Differentiation ◽  
Rat Model ◽  
Memory Impairment ◽  
Cyperus Rotundus ◽  
Model Of Alzheimer’S Disease

Intracerebral drug delivery in rats with lesion-induced memory deficits

1989 ◽  
Vol 71 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Matthew A. Howard ◽  
Alan Gross ◽  
M. Sean Grady ◽  
Robert S. Langer ◽  
Edith Mathiowitz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Radial Maze ◽  
Sebacic Acid ◽  
Performance Testing ◽  
Memory Deficits ◽  
Polymeric Drug Delivery ◽  
Polymeric Drug

✓ Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run an eight-arm radial maze, after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however, displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p < 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

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