Time-dependent effect of oligomeric amyloid-β (1–42)-induced hippocampal neurodegeneration in rat model of Alzheimer’s disease

Chennakesavan Karthick, Saravanan Nithiyanandan, Mohamed Musthafa Essa, Gilles J. Guillemin, Swaminathan K. Jayachandran, Muthuswamy Anusuyadevi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (Aβ) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that Aβ influences N-methyl d-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric Aβ(1–42) (oAβ1–42) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD. Methods: Aggregated forms of synthetic Aβ peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription–polymerase chain reaction. Results: oAβ1–42 decreased the gene expression level of α7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oAβ1–42 aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-β1–42 are highly expressed in 15 days after postinjection in hippocampus of adult rats. Conclusion: Acute exposure of oAβ1–42 modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments. Abbreviations: AD: Alzheimer’s disease, Aβ: amyloid-β; oAβ1–42: oligomeric amyloid-β 1–42 full length peptide; CAM: calmodulin; CNS: central nervous system; CR: Congo red; DG: dentate gyrus; EC: entorhinal cortex; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; IBO: ibotenic acid; NMDA: N-methyl d-aspartate; NMDAR: N-methyl d-aspartate receptor; NR2A: N-methyl d-aspartate receptor 2A; NR2B: N-methyl d-aspartate receptor 2B; ACh: acetylcholine; α7-nAChR: α7-nicotinic acetylcholine receptor; PBS: phosphate buffered saline; RAM: Radial Arm Maze; ThT: thioflavin T.

Original languageEnglish
JournalNeurological Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Amyloid
Alzheimer Disease
Cholinergic Receptors
Nicotinic Receptors
N-Methyl-D-Aspartate Receptors
Gene Expression
Messenger RNA
Hippocampus
Ibotenic Acid
Congo Red
Entorhinal Cortex
Peptides
Neurotransmitter Receptor
Amyloid beta-Peptides
Dentate Gyrus
Brain
N-Methylaspartate
Calmodulin
Aspartic Acid
Acetylcholine

Keywords

  • acetylcholine receptor
  • Alzheimer’s disease
  • amyloid-β
  • hippocampus
  • NMDA receptor
  • spatial learning and memory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Time-dependent effect of oligomeric amyloid-β (1–42)-induced hippocampal neurodegeneration in rat model of Alzheimer’s disease. / Karthick, Chennakesavan; Nithiyanandan, Saravanan; Essa, Mohamed Musthafa; Guillemin, Gilles J.; Jayachandran, Swaminathan K.; Anusuyadevi, Muthuswamy.

In: Neurological Research, 01.01.2018.

Research output: Contribution to journalArticle

Karthick, Chennakesavan ; Nithiyanandan, Saravanan ; Essa, Mohamed Musthafa ; Guillemin, Gilles J. ; Jayachandran, Swaminathan K. ; Anusuyadevi, Muthuswamy. / Time-dependent effect of oligomeric amyloid-β (1–42)-induced hippocampal neurodegeneration in rat model of Alzheimer’s disease. In: Neurological Research. 2018.
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author = "Chennakesavan Karthick and Saravanan Nithiyanandan and Essa, {Mohamed Musthafa} and Guillemin, {Gilles J.} and Jayachandran, {Swaminathan K.} and Muthuswamy Anusuyadevi",
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AU - Karthick, Chennakesavan

AU - Nithiyanandan, Saravanan

AU - Essa, Mohamed Musthafa

AU - Guillemin, Gilles J.

AU - Jayachandran, Swaminathan K.

AU - Anusuyadevi, Muthuswamy

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N2 - Objective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (Aβ) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that Aβ influences N-methyl d-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric Aβ(1–42) (oAβ1–42) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD. Methods: Aggregated forms of synthetic Aβ peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription–polymerase chain reaction. Results: oAβ1–42 decreased the gene expression level of α7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oAβ1–42 aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-β1–42 are highly expressed in 15 days after postinjection in hippocampus of adult rats. Conclusion: Acute exposure of oAβ1–42 modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments. Abbreviations: AD: Alzheimer’s disease, Aβ: amyloid-β; oAβ1–42: oligomeric amyloid-β 1–42 full length peptide; CAM: calmodulin; CNS: central nervous system; CR: Congo red; DG: dentate gyrus; EC: entorhinal cortex; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; IBO: ibotenic acid; NMDA: N-methyl d-aspartate; NMDAR: N-methyl d-aspartate receptor; NR2A: N-methyl d-aspartate receptor 2A; NR2B: N-methyl d-aspartate receptor 2B; ACh: acetylcholine; α7-nAChR: α7-nicotinic acetylcholine receptor; PBS: phosphate buffered saline; RAM: Radial Arm Maze; ThT: thioflavin T.

AB - Objective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (Aβ) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that Aβ influences N-methyl d-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric Aβ(1–42) (oAβ1–42) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD. Methods: Aggregated forms of synthetic Aβ peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription–polymerase chain reaction. Results: oAβ1–42 decreased the gene expression level of α7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oAβ1–42 aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-β1–42 are highly expressed in 15 days after postinjection in hippocampus of adult rats. Conclusion: Acute exposure of oAβ1–42 modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments. Abbreviations: AD: Alzheimer’s disease, Aβ: amyloid-β; oAβ1–42: oligomeric amyloid-β 1–42 full length peptide; CAM: calmodulin; CNS: central nervous system; CR: Congo red; DG: dentate gyrus; EC: entorhinal cortex; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; IBO: ibotenic acid; NMDA: N-methyl d-aspartate; NMDAR: N-methyl d-aspartate receptor; NR2A: N-methyl d-aspartate receptor 2A; NR2B: N-methyl d-aspartate receptor 2B; ACh: acetylcholine; α7-nAChR: α7-nicotinic acetylcholine receptor; PBS: phosphate buffered saline; RAM: Radial Arm Maze; ThT: thioflavin T.

KW - acetylcholine receptor

KW - Alzheimer’s disease

KW - amyloid-β

KW - hippocampus

KW - NMDA receptor

KW - spatial learning and memory

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