Morphofunctional Changes in Mauthner Neurons During Exposure to the Neuropeptide Kyotorphin

García-Nimo

et al. 2013

Front. Aging Neurosci.

In Alzheimer’s disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP) is an endogenous analgesic dipeptide (Tyr-Arg) for which there is evidence of eventual neuroprotective and neuromodulatory properties. The objective of this work was to study the possible correlation between KTP and phosphorylated tau protein (p-tau) levels in cerebro-spinal fluid (CSF) samples of AD patients. CSF samples were collected from 25 AD patients and 13 age-matched controls (N), where p-tau and KTP levels were measured. We found a statistically significant difference between p-tau/KTP values in AD and N groups with an inverse correlation between p-tau and KTP values in AD samples. These results suggest that in the future KTP may be a candidate biomarker for neurodegeneration and may be a lead compound to be used pharmacologically for neuroprotection.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuropeptide Kyotorphin (Tyrosyl-Arginine) has Decreased Levels in the Cerebro-Spinal Fluid of Alzheimer’s Disease Patients: Potential Diagnostic and Pharmacological Implications

García-Nimo

et al. 2013

Front. Aging Neurosci.

“…Derivatization seems to enable CNS-targeting. Besides analgesia, it has been hypothesized that KTP has neuromodulating and neuroprotective properties ( Nazarenko et al, 1999 ; Bocheva and Dzambazova-Maximova, 2004 ), as well as an antiepileptic effect ( Godlevsky et al, 1995 ) and neuroleptic activity affecting calcium-dependent currents in postsynaptic membrane ( Santalova et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

Amidated and Ibuprofen-Conjugated Kyotorphins Promote Neuronal Rescue and Memory Recovery in Cerebral Hypoperfusion Dementia Model

Santos¹,

Santos²,

Pinto³

et al. 2016

Front. Aging Neurosci.

103

Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer’s disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP–NH2) and KTP–NH2 linked to ibuprofen (IbKTP–NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP–NH2 or IbKTP–NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP–NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.

“…The habituation was estimated as total ambulation (trajectory length travelled for 1 minute during 5 min of observation). 12…”

Section: Open Field Test (Oft)mentioning

confidence: 99%

“…7 Additionally to its main antinociceptive activity, KTP has shown to exert neuroleptic, antiepileptic and neuroprotective effects. 8,12,13 Some KTP derivatives have been shown to prevent the cognitive impairment and neuronal damage in the hippocampus induced by chronic cerebral hypoperfusion and to suppress locomotors activity at a moderate rate. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Angelova¹,

Krumova²,

Dzhambazova

et al. 2021

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.