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

Angelova, Hristina; Pechlivanova, Daniela; Krumova, Ekaterina; Miteva‐Staleva, Jeny; Kostadinova, Nedelina; Dzhambazova, Elena; Landzhov, Boycho

doi:10.1007/s00726-019-02784-5

Cited by 8 publications

(9 citation statements)

References 70 publications

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“…33 We have previously shown that ICV infusion of KTP in a model of Alzheimer's disease prevented the disintegration of normal anxiety behavior in rats treated with streptozotocin. 13,16 The present results from the OFT showed a dose-dependent improvement of the habituation to a new environment of rats treated with KTP as compared to the controls. The only literature data found was related to the effects of two halogen analogs of KTP on the behavior, which demonstrated improved habituation to a new environment after two or three ICV injections in mice, while a single injection did not exert any effect on the exploration.…”

Section: Discussionsupporting

confidence: 55%

“…We have previously shown that KTP can prevent the development of Alzheimer's type of impairment of the recognition memory when the peptide was infused chronically before and after the injection of streptozotocin. 16 The present data revealed that KTP itself has not memory-enhancing action and its action in the Alzheimer's experimental model perhaps is a result of prevention against the deleterious impact of the streptozotocin both in the early and the late phase of the development of the experimental model. 13,16 Altogether, our results showed that KTP administered directly into the brain ventricles exerted its main antinociceptive effect without affecting negatively the blood and hippocampal carbonylated proteins or basic behavioral parameters related to exploration, motivation and memory formation in healthy rats.…”

Section: Discussionmentioning

confidence: 51%

“…14,15 The chronic intracerebroventricular (ICV) treatment with KTP displayed a mild protective effect on the deleterious consequences from an experimental model of Alzheimer's disease. 13,16…”

Section: Introductionmentioning

confidence: 99%

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Effects of the antinociceptive dipeptide L-tyrosine-L-arginine (kyotorphin) on the motivation, anxiety, and memory in rats

Angelova¹,

Krumova²,

Dzhambazova

et al. 2021

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Introduction: The endogenous dipeptide L-tyrosine-L-arginine (kyotorphin, KTP) is found in brain structures related to the processing of information for nociception, the control of emotions, and memory formation. Besides the antinociceptive effect of KTP, it has a mild protective activity against the deleterious influence of the brain hypoperfusion and streptozotocin on the behavior and memory.  Aim: We aimed to study the effects of the intracerebroventricular injection of effective antinociceptive doses of KTP on the motivational behavior, memory, and blood and hippocampal levels of the carbonylated proteins in healthy male adult Wistar rats. Materials and methods: We used a paw-pressure test for assessment of acute nociception, an open field test for assessment of exploration and habituation to a new environment, elevated plus maze test for the evaluation of anxiety-like behavior, and novel object recognition test for working memory. Carbonylated protein assay was used for the assessment of the oxidative impairment of the proteins. The results were analyzed by ANOVA. Results: The present data showed that all single doses of KTP exerted an antinociceptive effect, but this effect was not observed after chronic administration. Only the highest dose of 100 µg was able to induce anxiolytic and motor inhibiting effects. None of the doses used showed effects on the recognition memory or the level of the carbonylated protein.  Conclusion: Our results showed that KTP exerted its antinociceptive effect without affecting negatively the blood and brain carbonylated protein or basic behavioral parameters related to the exploration, motivation, and memory formation in healthy rats.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 51%

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Effects of the antinociceptive dipeptide L-tyrosine-L-arginine (kyotorphin) on the motivation, anxiety, and memory in rats

Angelova¹,

Krumova²,

Dzhambazova

et al. 2021

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“…Alzheimer’s disease is clinically divided into two types including sporadic AD (SAD) and familial AD (FD), and the SAD accounts for 95% of the all AD cases [ 16 ]. Intracerebroventricular (ICV) injection of streptozotocin (STZ) is a universally accepted method to establish the model of sporadic ADs [ 3 , 23 ]. Preclinical studies have found the memory and learning deficits along with the observation of cerebral atrophy, amyloid plaques, and neuroﬁbrillary tangles in STZ-treated rats [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Schisandrin ameliorates cognitive deficits, endoplasmic reticulum stress and neuroinflammation in streptozotocin (STZ)-induced Alzheimer’s disease rats

et al. 2020

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Schisandrin, an active component extracted from Schisandra chinensis (Turcz.) Baill has been reported to alleviate the cognitive impairment in neurodegenerative disorder like Alzheimer's disease (AD). However, the mechanism by which schisandrin regulates the cognitive decline is still unclear. In our study, intracerebroventricular injection of streptozotocin (STZ) was employed to establish AD model in male Wistar rats, and indicated dose of schisandrin was further administered. The Morris water maze test was performed to evaluate the ability of learning and memory in rats with schisandrin treatment. The results indicated that schisandrin improved the capacity of cognition in STZ-induced rats. The contents of pro-inflammatory cytokines in brain tissue were determined by ELISA, and the expressions of these cytokines were assessed by western-blot and immunohistochemistry. The results showed that treatment of schisandrin significantly reduced the production of inflammation mediators including tumor necrosis factor-α, interleukin-1β and interleukin-6. Further study suggested a remarkable decrease in the expressions of ER stress maker proteins like C/EBP-homologous protein, glucose-regulated protein 78 and cleaved caspase-12 in the presence of schisandrin, meanwhile the up-regulation of sirtuin 1 (SIRT1) was also observed in the same group. Additionally, the results of western-blot and EMSA demonstrated that schisandrin inhibited NF-κB signaling in the brain of STZ-induced rats. In conclusion, schisandrin ameliorated STZ-induced cognitive dysfunction, ER stress and neuroinflammation which may be associated with up-regulation of sirtuin 1 (SIRT1). Our study provides novel mechanisms for the neuroprotective effect of 3 schisandrin in AD treatment.

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“…Despite the encouraging recent data showing that intracerebroventricular (i.c.v) injection of KTP ameliorates memory impairments in a sporadic AD rat model ( Angelova et al., 2019 ), its weak activity when administered systemically ( Chen et al., 1998 ) renders KTP as an unrealistic pharmacological tool to fight AD. Amidated-kyotorphin (KTP-NH 2 ), is a KTP derivative capable of crossing the blood brain barrier (BBB) ( Ribeiro et al., 2011a ; Ribeiro et al., 2011b ), and with efficacy to decrease neuronal damage induced by cerebral hypoperfusion ( Sá Santos et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer’s Disease Pathophysiology

et al. 2020

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Kyotorphin (KTP, L-tyrosyl-L-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer's disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH 2 , when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid b peptide (Ab). Animals were treated for 20 days with KTP-NH 2 (32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Ab administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH 2 treatment, Ab-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Ab-injected rats that

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

Cited by 8 publications

References 70 publications

Effects of the antinociceptive dipeptide L-tyrosine-L-arginine (kyotorphin) on the motivation, anxiety, and memory in rats

Effects of the antinociceptive dipeptide L-tyrosine-L-arginine (kyotorphin) on the motivation, anxiety, and memory in rats

Schisandrin ameliorates cognitive deficits, endoplasmic reticulum stress and neuroinflammation in streptozotocin (STZ)-induced Alzheimer’s disease rats

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer’s Disease Pathophysiology

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