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Amyloid-beta (1-42) lesion of CA1 rat dorsal hippocampus reduces contextual fear memory and increases expression of microglial genes regulating neuroinflammation.
Behav Brain Res. 2020 Jun 30; 393:112795.BB

Abstract

Emerging evidence indicates that the pathogenesis of Alzheimer's disease (AD) is not confined to neuronal disruptions but robustly communicates with the brain's immune system. Genome-wide analysis suggests that several genes, which increase the risk for AD, encode for factors that regulate the glial clearance of misfolded proteins and the inflammatory reaction. This study reappraises the amyloid hypothesis by focusing on the impact of neuroinflammation in a beta-amyloid model of AD, how this possibly exacerbates the disease's progression, and the correlation between genes regulating neuroinflammation (CD33 and TREM2) with post-training recall. Male Sprague-Dawley rats were used for this study, randomly divided into a vehicle group of rats (n = 40) that were infused with phosphate-buffered saline (PBS) and an Aβ(1-42) group (n = 40) that were infused with the neurotoxin Aβ(1-42) peptide. Fear conditioning test (FCT) to assess fear memory was conducted pre and post-lesion. The polymerase chain reaction was performed to determine the expression levels of CD33 and TREM2 genes. Our results show that Aβ(1-42) lesion of the rat CA1 hippocampal subregion significantly reduces contextual fear memory, and this reduction was exacerbated as the post-lesion days increased. We also observed an increase in the expression levels of CD33 and TREM2 genes in the Aβ(1-42) lesioned groups compared to their corresponding vehicle groups. Taken together, the behavioral and gene expression data provide inferential evidence that Aβ(1-42) infusion impairs contextual memory by disrupting cellular pattern separation processes in the hippocampus, thus linking neuroinflammation to specific neural circuit disruption and cognitive deficit.

Authors+Show Affiliations

Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa. Electronic address: 217082125@stu.ukzn.ac.za.Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32619564

Citation

Shallie, Oluwadamilola F., and Musa V. Mabandla. "Amyloid-beta (1-42) Lesion of CA1 Rat Dorsal Hippocampus Reduces Contextual Fear Memory and Increases Expression of Microglial Genes Regulating Neuroinflammation." Behavioural Brain Research, vol. 393, 2020, p. 112795.
Shallie OF, Mabandla MV. Amyloid-beta (1-42) lesion of CA1 rat dorsal hippocampus reduces contextual fear memory and increases expression of microglial genes regulating neuroinflammation. Behav Brain Res. 2020;393:112795.
Shallie, O. F., & Mabandla, M. V. (2020). Amyloid-beta (1-42) lesion of CA1 rat dorsal hippocampus reduces contextual fear memory and increases expression of microglial genes regulating neuroinflammation. Behavioural Brain Research, 393, 112795. https://doi.org/10.1016/j.bbr.2020.112795
Shallie OF, Mabandla MV. Amyloid-beta (1-42) Lesion of CA1 Rat Dorsal Hippocampus Reduces Contextual Fear Memory and Increases Expression of Microglial Genes Regulating Neuroinflammation. Behav Brain Res. 2020 Jun 30;393:112795. PubMed PMID: 32619564.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid-beta (1-42) lesion of CA1 rat dorsal hippocampus reduces contextual fear memory and increases expression of microglial genes regulating neuroinflammation. AU - Shallie,Oluwadamilola F, AU - Mabandla,Musa V, Y1 - 2020/06/30/ PY - 2020/04/06/received PY - 2020/05/26/revised PY - 2020/06/27/accepted PY - 2020/7/4/pubmed PY - 2020/7/4/medline PY - 2020/7/4/entrez KW - Alzheimer’s disease KW - Amyloid beta KW - Contextual memory KW - Cornu ammonis 1 KW - Fear conditioning KW - Microglial genes SP - 112795 EP - 112795 JF - Behavioural brain research JO - Behav. Brain Res. VL - 393 N2 - Emerging evidence indicates that the pathogenesis of Alzheimer's disease (AD) is not confined to neuronal disruptions but robustly communicates with the brain's immune system. Genome-wide analysis suggests that several genes, which increase the risk for AD, encode for factors that regulate the glial clearance of misfolded proteins and the inflammatory reaction. This study reappraises the amyloid hypothesis by focusing on the impact of neuroinflammation in a beta-amyloid model of AD, how this possibly exacerbates the disease's progression, and the correlation between genes regulating neuroinflammation (CD33 and TREM2) with post-training recall. Male Sprague-Dawley rats were used for this study, randomly divided into a vehicle group of rats (n = 40) that were infused with phosphate-buffered saline (PBS) and an Aβ(1-42) group (n = 40) that were infused with the neurotoxin Aβ(1-42) peptide. Fear conditioning test (FCT) to assess fear memory was conducted pre and post-lesion. The polymerase chain reaction was performed to determine the expression levels of CD33 and TREM2 genes. Our results show that Aβ(1-42) lesion of the rat CA1 hippocampal subregion significantly reduces contextual fear memory, and this reduction was exacerbated as the post-lesion days increased. We also observed an increase in the expression levels of CD33 and TREM2 genes in the Aβ(1-42) lesioned groups compared to their corresponding vehicle groups. Taken together, the behavioral and gene expression data provide inferential evidence that Aβ(1-42) infusion impairs contextual memory by disrupting cellular pattern separation processes in the hippocampus, thus linking neuroinflammation to specific neural circuit disruption and cognitive deficit. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/32619564/AMYLOID-BETA_(1-42)_LESION_OF_CA1_RAT_DORSAL_HIPPOCAMPUS_REDUCES_CONTEXTUAL_FEAR_MEMORY_AND_INCREASES_EXPRESSION_OF_MICROGLIAL_GENES_REGULATING_NEUROINFLAMMATION L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(20)30494-0 DB - PRIME DP - Unbound Medicine ER -
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