Okadaic Acid and Hypoxia Induced Dementia Model of Alzheimer’s Type in Rats

  • Alka Kaushal
  • Willayat Yousuf Wani
  • Amanjit Bal
  • Kiran Dip Gill
  • Jyotdeep KaurEmail author
Original Article


Alzheimer’s disease (AD) is the most common cause of progressive decline of memory function in aged humans. To study about a disease mechanism and progression, animal models for the specific disease are needed. For AD, although highly valid animal models exist, none of the existing models recapitulates all aspects of human AD. The pathogenic mechanisms involved in AD are diverse and thus it is difficult to recapitulate human AD in model organisms. Intracerebroventricular (ICV) injection of okadaic acid (OKA), a protein phosphatase 2A (PP2A) inhibitor, in rats causes neurotoxicity associated with neurofibrillary degeneration. However, this model lacks amyloid pathology as observed in AD. We aimed at combining two different treatments and hence producing a better animal model of AD which may mimic most of the neuropathological, neurobehavioral, and neurochemical changes observed in AD. For this, OKA (200 ng) was microinjected bilaterally into the hippocampus of male Wistar rats followed by exposure of same rats to hypoxic conditions (10%) for 3 days. The result of which, the combination model exhibited tau hyperphosphorylation along with Aβ upregulation as evident by western blotting and immunohistochemistry. The observed changes were accompanied with dysfunction of neurotransmitter system, i.e., decreased acetylcholine activity and expression. This combinatorial model also exhibited cognitive deficiency which was assessed by Morris water maze and avoidance tests along with enhanced oxidative stress which is thought to be a major player in AD pathogenesis. Taken together, we established an easily reproducible and reliable rat model for sporadic dementia of Alzheimer’s type in rats which allows effective testing of new therapeutic strategies.


Alzheimer disease Amyloid beta Neurodegeneration Stereotaxic surgery Okadaic acid Hypoxia 


Beta amyloid


Neurofibrillary tangles


Okadaic acid


Reactive oxygen species


Paired helical filament


2′,7′-Dichlorodihydrofluorescein diacetate


Superoxide dismutase



This study was funded by Council of Scientific and Industrial Research (CSIR).

Compliance with Ethical Standards

Conflict of Interest

No conflicts of interest are declared by the authors.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiochemistryPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.The Ken and Ruth Davee Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Department of HistopathologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

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