MEMORY DEFICIT IN RATS SUBMITTED TO INDUCTION ALZHEIMER'S DISEASE IN INFUSION OF INTRACEREBRA L B-AMILOIDE1-42

Abstract

Alzheimer's disease (AD) was established as the neurodegenerative dementia, which leads to progressive and irreversible cognitive decline, memory loss, attention and judgment. lt is characterized by molecular injuries resulting from the accumulation of charged neuritic plaques of 13-amyloid and neurofibrillary tangles causing oxidative damage and inflammatory. Thus, the aim of this study was to evaluate the leaming and memory of rats seven days after infusion of 13-amiloide1-42. The 13-amiloide1-42 was prepared in saline protein (1ug / uL) and incubated at 37 º C for three days to form the aggregate. The animais were anesthetized with the combination of ketamine (100 mg / kg) and xylazine (10 mg / kg) intraperitoneally, and fixed in a stereotaxic route. The aggregate was infused directly in the hippocampus (SUL bilaterally) in the coordinates, AP : -3.5 mm; LL: ± 2.0 mm; DV: -3.5. The learning and memory was assessed using the Morris water maze. The apparatus consists of a circular water tank (120 cm diameter and 60 cm high) with an escape platform (12 .5 cm in diameter and 38 cm high) positioned invisible to the mice 2 cm below the water levei. The tank was divided by imaginary lines {N, S, L, and O) in four quadrants (1, 2, 3 and 4) and identified by the sarne geometrical symbols, which remained the sarne throughout the study. The animais were placed facing the geometric shapes and the exhaust time measured during four consecutive days (training) . ln the fifth and final day it was taken to the escape platform and computed the total residence time in the target quadrant (test). The maximum time for each step was 60s. This study was approved by Ethics Committee for Animal Use (CEUA) of the State University of Ceará (UECE) by the number 2542310/2015 . To analyze the learning we used the ANOVA two way with Bonferroni post-test. To verify differences in memory between the groups we used the Student t test. P <0 .05 significance levei was adopted . The results show no difference in learning the animais infused with 13-amiloide1-42 compareci with Sham group (Sham day 1=11,2±4,9, 2=7,5±5,1 3=6,67±4,8 4=7,8±4,1; Alzheimer day 1=12,9±4,0; 2=8,1±3,4; 3=5,7±2,1; 4=8,9±4,5), possibly caused by compensatory mechanisms, as DA begins with mild cognitive impairment (MCI) did not present symptoms such as aphasia, apraxia and agnosia. However, the memory test showed marked decline in latency time (memory) in the animais (Escape latency Sham=25,2±3,8; Alzheimer= 15,8±3,7 p<0,0001), suggesting that the aggregate is able to quickly lock the new memories formation mechanism, altering synaptic plasticity, in addition to discontinue synaptic function already after seven day infusion. Notwithstanding the Ar.. accumulation interrupts the correct release of neurotransmitter due to stimulation of presynaptic receptor. Therefore, it is concluded that the infusion of A13 1-42 was able to decrease the memory seven days after infusion without significant changes in learning.