Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice

Abstract Background Alzheimer's disease is accompanied by an abnormal high accumulation of cis-P tau. However, the long-term changes in behavior following tau accumulation remains under debate. The present study investigated the long-term effects of tauopathy on learning and memory, synaptic pl...

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Main Authors: Bakhtiarzadeh Fatemeh, Shahpasand Koorosh, Shojaei Amir, Fathollahi Yaghoub, Mirnajafi-Zadeh Javad
Format: Article
Language:English
Published: BMC 2023-05-01
Series:Behavioral and Brain Functions
Subjects:
Online Access:https://doi.org/10.1186/s12993-023-00211-0
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author Bakhtiarzadeh Fatemeh
Shahpasand Koorosh
Shojaei Amir
Fathollahi Yaghoub
Mirnajafi-Zadeh Javad
author_facet Bakhtiarzadeh Fatemeh
Shahpasand Koorosh
Shojaei Amir
Fathollahi Yaghoub
Mirnajafi-Zadeh Javad
author_sort Bakhtiarzadeh Fatemeh
collection DOAJ
description Abstract Background Alzheimer's disease is accompanied by an abnormal high accumulation of cis-P tau. However, the long-term changes in behavior following tau accumulation remains under debate. The present study investigated the long-term effects of tauopathy on learning and memory, synaptic plasticity, and hippocampal cell numbers. Results Cis-P tau was microinjected into the dorsal hippocampus to generate Alzheimer’s like-disease model in C57BL/6 mice. Cis-P tau injected animals showed a significant impairment in learning and memory in Y-maze and Barnes maze tests. In another group of animals, the generation of long-term potentiation (LTP) was evaluated in hippocampal slices 7 months after cis-P tau injection. LTP induction was disrupted only in the dorsal but not ventral hippocampal slices. The basal synaptic transmission was also reduced in dorsal hippocampal slices. In addition, hippocampal sampling was done, and the number of cells was assessed by Nissl staining. Obtained results indicated that the number of survived cells was significantly reduced in the dorsal and ventral hippocampus of cis P-tau injected animals compared to the animals in control group. However, the decrement of cell number was higher in the dorsal compared to the ventral hippocampus. Conclusions In conclusion, intra-hippocampal cis-P tau injection produced learning and memory impairment at 7 months after its injection. This impairment might result from LTP disruption and a significant decrease in the number of neurons in the dorsal hippocampus. Graphical Abstract
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spelling doaj.art-61384b579c5b473c8c05d9c19772f9c92023-05-28T11:23:17ZengBMCBehavioral and Brain Functions1744-90812023-05-0119111310.1186/s12993-023-00211-0Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in miceBakhtiarzadeh Fatemeh0Shahpasand Koorosh1Shojaei Amir2Fathollahi Yaghoub3Mirnajafi-Zadeh Javad4Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECRDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares UniversityDepartment of Physiology, Faculty of Medical Sciences, Tarbiat Modares UniversityAbstract Background Alzheimer's disease is accompanied by an abnormal high accumulation of cis-P tau. However, the long-term changes in behavior following tau accumulation remains under debate. The present study investigated the long-term effects of tauopathy on learning and memory, synaptic plasticity, and hippocampal cell numbers. Results Cis-P tau was microinjected into the dorsal hippocampus to generate Alzheimer’s like-disease model in C57BL/6 mice. Cis-P tau injected animals showed a significant impairment in learning and memory in Y-maze and Barnes maze tests. In another group of animals, the generation of long-term potentiation (LTP) was evaluated in hippocampal slices 7 months after cis-P tau injection. LTP induction was disrupted only in the dorsal but not ventral hippocampal slices. The basal synaptic transmission was also reduced in dorsal hippocampal slices. In addition, hippocampal sampling was done, and the number of cells was assessed by Nissl staining. Obtained results indicated that the number of survived cells was significantly reduced in the dorsal and ventral hippocampus of cis P-tau injected animals compared to the animals in control group. However, the decrement of cell number was higher in the dorsal compared to the ventral hippocampus. Conclusions In conclusion, intra-hippocampal cis-P tau injection produced learning and memory impairment at 7 months after its injection. This impairment might result from LTP disruption and a significant decrease in the number of neurons in the dorsal hippocampus. Graphical Abstracthttps://doi.org/10.1186/s12993-023-00211-0Alzheimer’s like diseaseCis P-tauDorsal and ventral hippocampusLearning and memory and synaptic plasticity
spellingShingle Bakhtiarzadeh Fatemeh
Shahpasand Koorosh
Shojaei Amir
Fathollahi Yaghoub
Mirnajafi-Zadeh Javad
Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice
Behavioral and Brain Functions
Alzheimer’s like disease
Cis P-tau
Dorsal and ventral hippocampus
Learning and memory and synaptic plasticity
title Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice
title_full Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice
title_fullStr Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice
title_full_unstemmed Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice
title_short Intra-hippocampal cis-P tau microinjection induces long-term changes in behavior and synaptic plasticity in mice
title_sort intra hippocampal cis p tau microinjection induces long term changes in behavior and synaptic plasticity in mice
topic Alzheimer’s like disease
Cis P-tau
Dorsal and ventral hippocampus
Learning and memory and synaptic plasticity
url https://doi.org/10.1186/s12993-023-00211-0
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