Jana Tchekalarova | Institute of Neurobiology, Bulgarian Academy of Sciences (original) (raw)

Papers by Jana Tchekalarova

Methods and Findings in Experimental and Clinical Pharmacology, 1998

The present study was undertaken to further evaluate the effects of angiotensinergic agents: angi... more The present study was undertaken to further evaluate the effects of angiotensinergic agents: angiotensin II (AII), its analogues sarmesin ([Sar1, Tyr(Me)4]AII) and sarilesin ([Sar1, Ile8]AII), as well as DuP 753, a nonpeptide selective AT1 receptor antagonist, on apomorphine stereotypy in rats thus providing further evidence for AII-DAergic receptor interactions. All drugs were administered intracerebroventricularly (i.c.v.). Stereotyped behavior was evoked by an i.p. injection of 3 mg/kg apomorphine. AII (0.1-5 micrograms) exerted a decrease on stereotypies (U-shaped); the effect being significant at doses of 1 and 2 micrograms. Sarmesin significantly increased apomorphine stereotypy at a dose of 5 micrograms and decreased it at a dose of 20 micrograms. Sarmesin (10 micrograms) reversed the decreasing effect of AII (2 micrograms) leading to a more pronounced increase of stereotypies. Sarilesin (5 micrograms), which by itself is inactive, also demonstrated antagonistic properties when injected 5 min before AII (2 micrograms). DuP 753 (100 micrograms) alone had no significant effect on apomorphine stereotypy, but injected 5 min before AII (2 micrograms) it reversed the decreasing effect of AII on stereotypy. Taken together, the results further confirm the hypothesis that AII closely interacts with DAergic neurotransmission, an effect which is mediated predominantly by AT1 receptors.

Behavioural Brain Research, 2001

The functional interaction between ANG (3-8) (ANG IV) and adenosine A 1 receptor related drugs in... more The functional interaction between ANG (3-8) (ANG IV) and adenosine A 1 receptor related drugs in passive avoidance (step-through) task in rats was studied in Wistar rats. ANG IV exerted dose-dependent (inverted-U) improvement of the retention while sarilesin (an angiotensin II analog) impaired this effect. Co-administration of theophylline and ANG IV, both in ineffective doses, enhanced the retention. The selective adenosine A 1 receptor agonist cyclopentyladenosine (CPA) attenuated ANG IV-induced memory enhancement.

Life Sciences, 2018

Aims: Experimental and clinical studies have demonstrated that components of renin-angiotensin sy... more Aims: Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT 1 receptor) in limbic structures, as well as the effect of the AT1 receptor antagonist losartan in a model of comorbid hypertension and epilepsy. Main methods: The expression of AT 1 receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE). The effect of losartan was studied on AT 1 receptor expression in epileptic rats that were treated for a period of 4 weeks after status epilepticus.

Acta morphologica et anthropologica, Nov 1, 2022

Physiology & Behavior

The pineal gland is suggested to be an essential area involved in the programming of fertility, g... more The pineal gland is suggested to be an essential area involved in the programming of fertility, growth, aging, and death of mammals via the released hormone melatonin.The present study aimed to ascertain the effect of melatonin deficit on several physiological and metabolic parameters, closely associated with the aging process, at certain stages of ontogenesis. Sham and rats with pinealectomy, operated at ages 3, 14, and 18-months, respectively, were tested two months later. Sham rats demonstrated an age-related decline of muscle strength, exercise endurance, motor activity, food intake, calorimetric parameters, and impaired lipid profile. Pinealectomy reduced the maximal time to exhaustion and body weight gain while diminished motor activity, food intake, O2 consumption, CO2 production, and energy expenditure during the Dark phase in the youngest rat group. In addition, melatonin deficit elevated arterial blood pressure (systolic, diastolic, and mean arterial pressure) and increased serum glucose and triglyceride level in 3-month-old rats while decreased the liver enzyme activity in 14-month-old rats. In conclusion, the present study brought new insights confirming the complex impact of melatonin deficit on important physiological, metabolic and biochemical markers related to aging and demonstrated for the first time that the lack of melatonin hormone is harmful in young adult rats.

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Despite the plethora of anti-epileptic drugs (AEDs) available, in one third of patients with epil... more Despite the plethora of anti-epileptic drugs (AEDs) available, in one third of patients with epilepsy the seizure control remains poor. Due to the similarity between the mechanisms of epileptogenesis and neuropathic pain, some AEDs have an indication for pain treatment. All of them, however, show adverse effects. There has been a recent strengthening of the specific regulatory restrictions for some AEDs, due to the recognised risk of fetal harm. The aim of the present study is to investigate the anti-convulsive and analgesic activity of newly synthesised hydrazide-hydrazone derivatives bearing 2Hchromene and coumarin scaffold in ICR mice. Male ICR mice were used (8 per group). Maximal electroshock (MES) test was applied to study anti-convulsive activity. Two tests were used to assess analgesic activity, i.e. the hot plate test and the formalin test. Antiseizure activity has been observed for p-chlorphenyl, 2-furyl and p-methoxyphenyl substituted derivatives of coumarin-hydrazide/hydrazones (4a, 4c) (ED50 99.71mg/kg, 81.29 mg/kg respectively, MES test), and for p-chlorphenyl and 2-furyl substituted derivatives of 2H-chromene based hydrazide/hydrazone (8a, 8b) (ED50 87.63 mg/kg and 12.51 mg/kg, respectively, MES test). During the hot plate test, 8b significantly increased the latency time when compared to the control group (median values 53.5 vs. 25 sec, p<0.05). During the first phase of the formalin test, 4a and 4c significantly shortened the licking time (median values 15 and 25 sec, respectively) when compared to the control group (51 sec, p<0.05). The investigated substances did not demonstrate anti-nociceptive effects during the second phase of the formalin test. The results from this study indicate that 4a, 4c and 8b possess anti-nociceptive and anti-convulsive effects. The connection between the chemical structure of the investigated compounds and the observed is to be elucidated by ongoing studies. These studies will also reveal certain molecular mechanisms of action.

Pharmaceuticals

The emergence of diverse peptide derivatives has been due to constant efforts to find a specific ... more The emergence of diverse peptide derivatives has been due to constant efforts to find a specific peptide with pronounced biological activity for effective application as a therapeutic. Spinorphin-peptide products have been reported to possess various applications and properties. In the present study, spinorphin peptides with a rhodamine residue and a modification in the amino acid backbone were synthesized by a solid-phase method using Fmoc chemistry. The results obtained from the spectral and electrochemical techniques used: Scanning electron microscopy (SEM), UV-vis, fluorescence, infrared spectroscopy (IR), and voltammetry were used to elucidate the structural characteristics and some physicochemical properties to gain insight into their behavior in the solid state and in aqueous solutions with different pHs. Both Rh-S5 and Rh-S6 had compound anticonvulsant effect comparable to Rh-S against psychomotor seizures at the highest dose of 20 μg. Furthermore, Rh-S6 showed a strong abil...

European Neuropsychopharmacology, 2019

International Journal of Molecular Sciences, Feb 3, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

The selective AT1 receptor antagonist Losartan has been shown to have neuroprotective and anticon... more The selective AT1 receptor antagonist Losartan has been shown to have neuroprotective and anticonvulsant effect in acute seizure models [ref:1]. The aim of the present study was to analyze the effect of chronic Losartan treatment during epileptogenesis on diurnal rhythms of behavior in Wistar[for full text, please go to the a.m. URL]

19 February, 2016, Sofia, Bulgaria Bulgarian Society of Physiological Sciences Sofia branch Scien... more 19 February, 2016, Sofia, Bulgaria Bulgarian Society of Physiological Sciences Sofia branch Scientific Meeting, 19 Feb, 2016 2 LOCAL ORGANIZING COMMITTEE Assoc. Prof. Elena Dzhambazova, PhD Assist. Prof. Milena Mihailova, PhD Assist. Prof. Rene Mileva, PhD Assist. Prof. Polina Mateeva, PhD Assist. Prof. Boris Kadinov, PhD Bulgarian Society of Physiological Sciences Sofia branch Scientific Meeting, 19 Feb, 2016 3 Programme Overview

International Journal of Molecular Sciences

The hallmark of aging is an organism’s difficulty to maintain proper homeostasis, leading to a di... more The hallmark of aging is an organism’s difficulty to maintain proper homeostasis, leading to a disrupted balance between the endogenous antioxidant system and the production of free radicals, a progressive inflammatory process, and increased susceptibility to (neurodegenerative diseases [...]

Dyes and Pigments

ABSTRACT In the present study, a novel analogue of azobenzene-containing hemorphin-4 has been syn... more ABSTRACT In the present study, a novel analogue of azobenzene-containing hemorphin-4 has been synthesized and investigated for assessment of spectral, electrochemical, and biological effects. The synthesis was achieved by a modified solid-phase peptide synthesis (SPPS) by Fmoc-strategy. This compound represents a newly synthesized and unstudied peptide-based chemosensor bearing azobenzene side-chain with different spectral and electrochemical properties in the two trans-/cis-states depending on the solvent polarity. Their fluorescence intensity, as well as voltammetric behavior, was found to depend on both the polarity of the solvents and the type of isomers of the azopeptide compound. The influence of the metal ions such as Zn 2+ , Ni 2+ , and Cu 2+ on the fluorescence emission intensity of trans-forms in a water solution of the azopeptide has been also studied. Both isomer forms have shown significant pH dependence, as the fluorescence peak and intensity are significantly distinguished in acidic and neutral medium. The electrochemical behavior before and after 90 min UV illumination was investigated using a cyclic voltammetric mode at three-electrode system with HMDE electrode as the working electrode. The novel biopeptide Azo-Tyr-Pro-Trp-Thr-NH2 was explored in vivo for potential anticonvulsant activity by 6-Hz seizure test and maximal electroshock test (MES) in ICR mice. The cis-Az-H4 isomer showed stronger potency than the trans-Az-H4 against both the 6 Hz-induced psychomotor seizures and tonic-clonic seizures in the maximal electroshock test with 100 % protection demonstrated at the lowest dose of 1 μg administered intracerebroventricularly in mice. The effect of 1 and 5 μg cis-Az-H4 and 5 μg trans-Az-H4 was comparable to the positive control valproate in the 6-Hz test. None of the tested isomers displayed neurotoxicity in the rotarod test. Our results suggest that modified biopeptide in the N-terminus of hemorphin-4 with azobenzene deserve further exploration as a promising candidate with both anticonvulsant activity and as a chemosensor for pH determination.

Drug Development Research, 2019

VV-Hemorphin-5 is an endogenous opioid peptide of the Hemorphin family with affinity at opioid re... more VV-Hemorphin-5 is an endogenous opioid peptide of the Hemorphin family with affinity at opioid receptors. A series of C-amide analogues have been synthesized, based on the structure of VV-Hemorphin-5, modified at position 1 and 7 by the un/natural amino acids (Aa8-Val-Val-Tyr-Pro-Trp-Thr-Gln-NH 2 and Val-Val-Tyr-Pro-Trp-Thr-Aa1-NH 2) using SPPS, Fmoc-chemistry. The peptide derivatives were evaluated for their anticonvulsant activity in three acute seizure tests in male ICR mice, the maximal electroshock (MES), the 6 Hz psychomotor seizure test, and the timed intravenous pentylenetetrazole (ivPTZ) infusion test. Their neurotoxicity was assessed in the rotarod test. Among the tested peptide analogues, V4 showed anticonvulsant activity in the three seizure tests that was comparable to the VV-Hemorphin-5 (V1) used as a positive control. While V5, V6, and V7 peptide derivatives exhibited anticonvulsant activity in the MES and 6 Hz test, they were inactive (V7) or showed pro-convulsant effect (V5 and V6) in the i.v. PTZ test. At a dose of 10 μg/mouse the peptide V2 was effective against clonic seizures induced by PTZ. Motor coordination was not affected by newly developed analogues of VV-Hemorphin-5. Docking study results suggest that kappa opioid receptor binding could be the mechanism of action of peptide derivatives with anticonvulsant activity. The results suggest that incorporation of nonproteinogenic and/or natural amino acids at position 1 and 7 of the VV-Hemorphin-5 scaffold deserve further evaluation in models of epilepsy and derivatization.

Physiological Research, 2011

Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in corti... more Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules – highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 – were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental...

Proceedings of the Bulgarian Academy of Sciences

Untoward events during pregnancy negatively affect offspring mental development. We investigated ... more Untoward events during pregnancy negatively affect offspring mental development. We investigated sex-dependent differences of emotional problems in offspring with a history of prenatal stress (PNS). Female rats demonstrated decreased anxiety-like behaviour in comparison to male controls, shown in the light-dark test. Male and female offspring of prenatally stressed mothers were characterized by higher anxiety levels, compared to unstressed controls. PNS induced depression-like behaviour in both sexes without differences among them, indicated with decreased intake of sweet solution in the sucrose consumption tests and increased immobility time spent in the forced swim test. Control females showed higher plasma corticosteroid (CORT) concentrantions after acute stress and decreased recovery (120 min after the stressor) than control males. Both male and female PNS-offspring were with elevated levels of CORT in the plasma, which remained high 120 min after application of the stressogenic...

International Journal of Molecular Sciences, 2022

The pineal gland regulates the aging process via the hormone melatonin. The present report aims t... more The pineal gland regulates the aging process via the hormone melatonin. The present report aims to evaluate the effect of pinealectomy (pin) on behavioral and oxidative stress-induced alterations in cholesterol and sphingomyelin (SM) levels in young adult, mature and aging rats. Sham and pin rats aged 3, 14 and 18 months were tested in behavioral tests for motor activity, anxiety, and depression. The ELISA test explored oxidative stress parameters and SM in the hippocampus, while total cholesterol was measured in serum via a commercial autoanalyzer. Mature and aged sham rats showed low motor activity and increased anxiety compared to the youngest rats. Pinealectomy affected emotional responses, induced depressive-like behavior, and elevated cholesterol levels in the youngest rats. However, removal of the pineal gland enhanced oxidative stress by diminishing antioxidant capacity and increasing the MDA level, and decreased SM level in the hippocampus of 14-month-old rats. Our findings...