Amino Acids

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Moderate protective effect of Kyotorphin against the late consequences of intracerebroventricular streptozotocin model of Alzheimer’s disease

  • Hristina Angelova
  • Daniela PechlivanovaEmail author
  • Ekaterina Krumova
  • Jeny Miteva-Staleva
  • Nedelina Kostadinova
  • Elena Dzhambazova
  • Boycho Landzhov
Original Article


The established decrease in the level of endogenous kyotorphin (KTP) into the cerebrospinal fluid of patients with an advanced stage of Alzheimer’s disease (AD) and the found neuroprotective activity of KTP suggested its participation in the pathophysiology of the disease. We aimed to study the effects of subchronic intracerebroventricular (ICV) treatment (14 days) with KTP on the behavioral, biochemical and histological changes in rats with streptozotocin (STZ-ICV)-induced model of sporadic AD (sAD). Three months after the administration of STZ-ICV, rats developed increased locomotor activity, decreased level of anxiety, impaired spatial and working memory. Histological data from the STZ-ICV group demonstrated decreased number of neurons in the CA1 and CA3 subfields of the hippocampus. The STZ-ICV group was characterized with a decrease of total protein content in the hippocampus and the prefrontal cortex as well as increased levels of the carbonylated proteins in the hippocampus. KTP treatment of STZ-ICV rats normalized anxiety level and regained object recognition memory. KTP abolished the protein loss in prefrontal cortex and decrease the neuronal loss in the CA3 subfield of the hippocampus. STZ-ICV rats, treated with KTP, did not show significant changes in the levels of the carbonylated proteins in specific brain structures or in motor activity and spatial memory compared to the saline-treated STZ-ICV group. Our data show a moderate and selective protective effect of a subchronic ICV administration of the dipeptide KTP on the pathological changes induced by an experimental model of sAD in rats.


Kyotorphin Alzheimer’s disease Anxiety Memory Hippocampus 



The research was supported by Grant 18/2016 of the Medical University of Sofia, Bulgaria.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experiments were approved by Bulgarian Food Safety Agency (No 144/04.08.2021) that is in accordance with EC Directive 2010/63/EU for animal experiments.


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© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of NeurobiologyBulgarian Academy of SciencesSofiaBulgaria
  2. 2.Institute of MicrobiologyBulgarian Academy of SciencesSofiaBulgaria
  3. 3.Faculty of MedicineSofia UniversitySofiaBulgaria
  4. 4.Department of AnatomyMedical University-SofiaSofiaBulgaria

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