Effects of L-thyrosyl - L-arginine (kyotorphin) on the behavior of rats and goldfish

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%

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.

“…In this case, the necessity for implantation of electrodes, which hinder studying of the free behavior of the object (goldfish), is ruled out, and simultaneous experiments on a number of the animals (fishes) become possible. A technique of simultaneous application of the substances to both MNs localized in the medulla of the fish has been developed and is now extensively used in our laboratory [18,19]. Our study was aimed at: (i) examination of the effects of separate applications of Glu and DA, as well as of combined applications of these agents or their combinations with natural long-lasting vestibular stimulation, on the functional state of MNs, which determines the ability of fishes to perform turnings in the course of motor behavior, and (ii) examination of morphological consequences of such applications; the latter approach may help us to understand structural mechanisms responsible for disturbances of the functional balance between these neurotransmitter systems at the cellular level.…”

Section: Introductionmentioning

confidence: 99%

Morphofunctional effects of applications of glutamate and dopamine on the goldfish Mauthner neurons

et al. 2006

In the goldfish, we studied the effects of intramedullar applications of glutamate (Glu), dopamine (DA), and of long-lasting rotational stimulation on the functional activity, dimensional characteristics, and ultrastructure of Mauthner neurons (MNs). Applications of Glu, especially when combined with rotational stimulation, were found to result in suppression of the function of MNs, in a decrease in their dimensions and lengths of desmosome-like contacts (DLCs, whose structure is determined by filamentous actin) in afferent mixed and chemical synapses, and in destruction of actin microfilaments in the cytoskeleton of MNs. Applications of DA, vice versa, induced an increase in the resistance to the effects of long-lasting stimulation and stabilized the dimensions of MNs; the length of DLCs increased in afferent synapses of both the above types, and the number of fibrillar actin bridges in the DLC cleft of mixed synapses also increased. Bundles of the actin filaments, which were preserved after stimulation, appeared in the cytoskeleton of MNs. Testing of the action of neurotransmitters on actin preparations in vitro showed that Glu entirely depolymerizes filamentous actin, while DA, vice versa, polymerizes monomeric actin. Thus, the Glu-and DA-induced reactions are similar in their types and are of a reciprocal nature both in the actin cytoskeleton of MNs in situ and in purified actin in vitro; these effects correlate with suppression of the functional state of MNs under the influence of Glu and with stabilization of this state under the influence of DA. These results agree with the concept on the roles of depolymerization and polymerization of actin in changes of the morphofunctional state of MNs and show that actin of the cytoskeleton of MNs is a cellular target for the actions of Glu and DA. The similarity between the effects of tested neurotransmitters on actin in MNs in situ and in cell-free preparations in vitro allows us to hypothesize that these transmitters can penetrate into the neuron.

“…Published papers have explored KTP role as antiepileptic (Godlevsky et al, 1995), thermoregulator (Sakurada et al, 1983), anti-hibernation regulator (Ignat’ev et al, 1998) and stress (Summy-Long et al, 1998) and behavior (Kolaeva et al, 2000) modulators.…”

Section: Ktpwas Clustered In Classes According To Regular Intervals Omentioning

confidence: 99%

“…Behavioral studies in rats and goldfish showed KTP reduced exploratory behavior mediated probably by the monoaminergic brain systems (Kolaeva et al, 2000). …”

Section: Ktpwas Clustered In Classes According To Regular Intervals Omentioning

confidence: 99%

Pharmacological Potential of the Endogenous Dipeptide Kyotorphin and Selected Derivatives

2017

The endogenous peptide kyotorphin (KTP) has been extensively studied since it was discovered in 1979. The dipeptide is distributed unevenly over the brain but the majority is concentrated in the cerebral cortex. The putative KTP receptor has not been identified yet. As many other neuropeptides, KTP clearance is mediated by extracellular peptidases and peptide transporters. From the wide spectrum of biological activity of KTP, analgesia was by far the most studied. The mechanism of action is still unclear, but researchers agree that KTP induces Met-enkephalins release. More recently, KTP was proposed as biomarker of Alzheimer disease. Despite all that, KTP limited pharmacological value prompted researchers to develop derivatives more lipophilic and therefore more prone to cross the blood–brain barrier (BBB), and also more resistant to enzymatic degradation. Conjugation of KTP with functional molecules, such as ibuprofen, generated a new class of compounds with additional biological properties. Moreover, the safety profile of these derivatives compared to opioids and their efficacy as neuroprotective agents greatly increases their pharmacological value.