title: Alzheimer's disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior.
abstract: OBJECTIVE
  Amyloid-beta (Aβ) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer's disease (AD), but soluble oligomeric Aβ is considered to be more potent and has been hypothesized to directly impair learning and memory. Also, evidences from some clinical studies indicated that Aβ oligomer formation is the major cause for early AD onset. However, the biochemical mechanism involved in the oligomer-induced toxicity is not very well addressed. So, thise present study was undertaken to study the effects of single intracerebroventricular (icv) injection of protofibrillar Aβ 1-42 on the behavioral and biochemical profile in rats.
  
  
  METHODS
  Rats were divided into two groups (n = 8 per group): (1) sham control group and (2) Aβ 1-42 injected group. A single dose of protofibrillar Aβ 1-42 (5 ul) through icv injection was bilaterally administered into the dorsal hippocampus, while sham control animals were administered with 5 µl of vehicle.
  
  
  RESULTS
  The results demonstrated that the protofibrillar Aβ significantly inhibited long-term memory retention and increased anxiety levels as shown by the behavioral studies. The amyloid deposits were present inside the brain even six weeks after injection as confirmed by thioflavin-T staining and the neurodegeneration induced by these deposits was confirmed by Nissl's staining in hippocampal and cortical regions. The amyloid aggregates induced reactive oxygen species (ROS) production, acetylcholinesterase activity, nitrite levels, lipid peroxidation, and inhibited antioxidant enzyme activity in hippocampus, cortex, and striatum regions of rat brain after six weeks.
  
  
  CONCLUSIONS
  The present study indicated that protofibrillar Aβ 1-42 injection altered long term memory, induced anxiety-like behavior and also developed Alzheimer's disease like pathology in rats.
authors.affiliation: a Department of Biophysics, Basic Medical Sciences Block II , Panjab University , Chandigarh , India.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Sharma
authors.affiliation: a Department of Biophysics, Basic Medical Sciences Block II , Panjab University , Chandigarh , India.
authors.forename: Sonia
authors.initials: S
authors.lastname: Verma
authors.affiliation: a Department of Biophysics, Basic Medical Sciences Block II , Panjab University , Chandigarh , India.
authors.forename: Monika
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: a Department of Biophysics, Basic Medical Sciences Block II , Panjab University , Chandigarh , India.
authors.forename: Avneet
authors.initials: A
authors.lastname: Saini
authors.affiliation: a Department of Biophysics, Basic Medical Sciences Block II , Panjab University , Chandigarh , India.
authors.forename: Bimla
authors.initials: B
authors.lastname: Nehru
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000150:complications* / Q000401:mortality; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001007:Anxiety / Q000209:etiology*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D007276:Injections, Intraventricular; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000633:toxicity*; D066329:Protein Aggregates / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D009573:Nitrites; D010446:Peptide Fragments; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D000110:Acetylcholinesterase
keywords: AChE, Acetylcholinesterase; AD, Alzheimer’s disease; APP, Amyloid precursor protein; Alzheimer’s disease; Amyloid beta 1-42; Anxiety; Aβ, Amyloid beta; CA1, Cornus ammonis; DCFH-DA, 2,7-dichlorofluorescein diacetate; DMSO, Dimethylsulphoxide; LPO, lipid peroxidation; LTP, Long term potentiation; MDA, Malondialdehyde; Memory retention; NFT, neurofibrillary tangle; Oxidative stress; ROS, Reactive oxygen species; SOD, Superoxide dismutase; TBA, Thiobarbituric acid; Th-T, Thioflavin-T; icv, intracerebroventricular