scholarly journals Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-βPrecursor Protein/Presenilin 2 Mouse Model of Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Yasushi Kishimoto ◽  
Kai Fukumoto ◽  
Mika Nagai ◽  
Ayaka Mizuguchi ◽  
Yuiko Kobashi
Keyword(s):  
Mouse Model ◽  
Critical Role ◽  
Memory Deficits ◽  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Model Of Alzheimer’S Disease ◽  
Swedish Mutation ◽  
Presenilin 2 ◽  
Tg2576 Mice

Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role inγ-secretase-mediated cleavage of amyloid-βprecursor protein (APP) and the subsequent generation ofβ-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memory deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the human APP with the Swedish mutation (Tg2576 mice). In the present study, an APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice. Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10–12 months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3 months of age, but significant memory impairment was observed from the age of 4 months. The cognitive impairment was more prominent at ages of 6 and 10–12 months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older showed significantly impaired fear memory. These results show that PS2 mutation significantly accelerates the onset of fear memory deficits in the APP AD model mice.

scholarly journals Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina F. de Veij Mestdagh ◽  
Jaap A. Timmerman ◽  
Frank Koopmans ◽  
Iryna Paliukhovich ◽  
Suzanne S. M. Miedema ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Memory Performance ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.

scholarly journals Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Toshihiko Toda ◽  
Yoshihiro Noda ◽  
Genzo Ito ◽  
Masahiro Maeda ◽  
Takahiko Shimizu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Memory Impairment ◽  
Amyloid Β Protein ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Accumulation ◽  
Presenilin 2 ◽  
Tg2576 Mice

In order to clarify the pathophysiological role of presenilin-2 (PS2) carrying the Volga German Kindred mutation (N141I) in a conventional mouse model of Alzheimer's disease (AD) expressing amyloid precursor protein (APP) with the Swedish mutation (Tg2576 line), we generated a double transgenic mouse (PS2Tg2576) by crossbreeding the PS2 mutant with Tg2576 mice. Here, we demonstrate that the PS2 mutation induced the early deposition of amyloid β-protein (Aβ) at 2-3 months of age and progressive accumulation at 4-5 months of age in the brains of the mutant mice. The PS2 mutation also accelerated learning and memory impairment associated with Aβ accumulation at 4-5 months of age in Tg2576 mice. These results suggest that the PS2 mutation causes early cerebral amyloid accumulation and memory dysfunction. PS2Tg2576 mice are a suitable mouse model for studying amyloid-lowering therapies.

scholarly journals Reversal of Impaired Hippocampal Long-Term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors

2012 ◽  
Vol 72 (3) ◽  
pp. 182-190 ◽  
Author(s):  
Hanoch Kaphzan ◽  
Pepe Hernandez ◽  
Joo In Jung ◽  
Kiriana K. Cowansage ◽  
Katrin Deinhardt ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Term Potentiation

scholarly journals The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Miguel Antonio Xavier de Lima ◽  
Marcus Vinicius C Baldo ◽  
Fernando A Oliveira ◽  
Newton Sabino Canteras
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Fear Memory ◽  
Anterior Cingulate ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Life Threatening ◽  
Learned Fear ◽  
Predator Threat ◽  
Made In

Predator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. The experiments were made in mice and revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits.

scholarly journals The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats

2021 ◽  
Author(s):  
Miguel Antonio Xavier de Lima ◽  
Marcus Vinicius C. Baldo ◽  
Fernando A. Oliveira ◽  
Newton Sabino Canteras
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Fear Memory ◽  
Anterior Cingulate ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Life Threatening ◽  
Memory Acquisition ◽  
Learned Fear ◽  
Predator Threat

ABSTRACTPredator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. Ours results revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits (i.e., predator- and conspecific-responsive circuits).

scholarly journals Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats

2018 ◽  
Vol 45 (6) ◽  
pp. 2529-2539 ◽  
Author(s):  
Shuhua Lai ◽  
Gangwei Wu ◽  
Zhixian Jiang
Keyword(s):  
Critical Role ◽  
Fear Memory ◽  
Fear Extinction ◽  
Chromosomal Protein ◽  
Single Prolonged Stress ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Memory Extinction ◽  
Prolonged Stress ◽  
Tlr4 Antagonist

Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

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