Alzheimer’s disease (AD)

Alzheimer’s disease (AD) selleck chemicals llc is the leading cause of dementia in the elderly, affecting more than 35 million people worldwide [1]. Currently, confirmation of a clinical diagnosis of AD still requires post mortem identification of parenchymal amyloid beta (A??) deposits and intra-neuronal neurofibrillary tangles composed of abnormally phosphorylated tau protein [2-5] and severe loss of brain tissue [6-8]. In the near future, cerebrospinal fluid (CSF) measures of A?? and tau or amyloid imaging may be utilized to provide pre-mortem confirmation of the AD diagnosis. Senile amyloid plaques are found in large numbers in the limbic system, including amygdala (AD is often referred to as ‘limbic dementia’ [9]), hippocampus, and associative cortices which are affected first during the disease progression [10-18].

Transgenic mice, over-expressing the mutated human amyloid precursor protein (APP) gene, provide a valuable tool for investigating the associations between amyloidosis, neuronal dysfunction, and cognitive impairment [19-23]. In the present study, we investigated the age-progressing A?? plaque burden and corresponding changes in conditioned fear memory in a transgenic mouse model, denoted CRND8. Previous characterizations of this model revealed impairments in spatial reference [24-26] and spatial working [27] memory, and in associative learning of conditioned taste aversion [28]. Other abnormalities reported in CRND8 mice included increased stereotypic behavior [29], brain inflammation [30] and increased sensitivity to experimentally induced seizures [31].

In our study, we adopted a delay fear conditioning (FC) training paradigm in which an initially neutral conditioned stimulus (CS), usually a tone, is simultaneously presented or co-terminates with an unconditioned stimulus (US), typically a foot-shock [32,33]. Following the CS-US pairing(s), mice display an anti-predatory freezing response both in the presence of a salient CS (tone conditioned fear memory) or when being placed in the original training chamber in which they experienced the US (contextual fear conditioning memory). It has been shown that the contextual fear memory depends on an intact hippocampus [34,35], while the cued fear memory depends on an intact amygdala [36,37].

The aim of the present study was to evaluate the contextual Entinostat and cued fear memory of CRND8 mice at the age of three, six, and 12 months, which corresponded to the onset of e-book low, moderate, and severe A?? plaque deposition in the brain of these mice [38], and to associate the A?? plaque burden with the context and tone memory indices. The results demonstrated that the A?? plaque burden significantly increased within the studied age range, and it was significantly associated with an overall impairment in contextual and tone fear memory in CRND8 mice. The oldest, 12 month-old, CRND8 mice showed impairment in both types of memory.

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