Jana TchekalarovaBulgarian Academy of Sciences | BAS · Institute of Neurobiology
Jana Tchekalarova
PhD in pharmacology
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185
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Publications (185)
In the search for Alzheimer’s disease (AD) therapies, most animal models focus on familial AD, which accounts for a small fraction of cases. The majority of AD cases arise from stress factors, such as oxidative stress, leading to neurological changes (sporadic AD). Early in AD progression, dysfunction in γ-secretase causes the formation of insolubl...
The novel cinnamic acid (CA) ( H4‐CA, H5‐CA , and H7‐CA ) and caffeic acid (KA) ( H4‐KA, H5‐KA , and H7‐KA ) hemorphin analogs have recently been synthesized and their trans isomers have been tested for antiseizure and antinociceptive activity. In the present study, the cis forms of these compounds were tested and compared with their trans isomers...
Memory decline is considered a normal part of aging, while the relationship between melatonin deficiency and cognitive function is complex and not fully understood. The present study investigated the role of melatonin deficiency functioning as a hormone at different ages on working and short-term recognition and spatial memory in rats. An age-relat...
Both hypertension and aging are known to increase the vulnerability of the brain to neurovascular damage, resulting in cognitive impairment. The present study investigated the efficacy of the antihypertensive drug losartan on age-and hypertension-associated cognitive decline and the possible mechanism underlying its effect in spontaneously hyperten...
Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatoni...
The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well-established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within the BLA governs these modulatory effects. However, most current evidence has been obtained...
The discovery of new peptides and their derivatives is an outcome of ongoing efforts to identify a peptide with significant biological activity for effective usage as a possible therapeutic agent. Spinorphin peptides have been documented to exhibit numerous applications and features. In this study, biologically active peptide derivatives based on n...
A plethora of pathophysiological events have been shown to play a synergistic role in neurodegeneration, revealing multiple potential targets for the pharmacological modulation of Alzheimer’s disease (AD). In continuation to our previous work on new indole- and/or donepezil-based hybrids as neuroprotective agents, the present study reports on the b...
Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and...
Some new hemorphin-4 analogs with structures of Xxx-Pro-Trp-Thr-NH2 and Tyr-Yyy-Trp-Thr-NH2, where Xxx is 2-amino-3-(4−hydroxy-2,6-dimethylphenyl)propanoic acid or 2-amino-3-(4-dibenzylamino-2,6-dimethylphenyl)propanoic acid, and Yyy is (2S,4S)-4-amino-pyrrolidine-2-carboxylic acid, were synthesized and characterized by electrochemical and spectral...
Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency. It...
The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within BLA governs these modulatory effects. However, most of the current evidence has been obtai...
Background Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate their inherited life "clock. " The present study aimed to explore the impact of plasma melatonin deficiency on anxiety responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock protein...
Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate
their inherited life “clock.” The present study aimed to explore the impact of plasma melatonin deficiency on anxiety
responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock
proteins (Hsp) 70 a...
Based on the pharmacophore model of opioid receptors, our team recently synthesized a series of short‐chain hemorphin peptide analogs containing non‐natural amino acids. They demonstrated anticonvulsant and antinociceptive activity with low neurotoxicity. In the present study, a series of novel bioconjugates of N-modified hemorphin analogs containi...
A reduction in melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding the molecular processes of melatonin-related signaling is critical for intervention in AD progression. Recently, we synthesized a series of melatonin analogues with donepezil fragments and tested them in silico and in vitro. In this stud...
A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of...
Background
The hormone melatonin has an advantage compared to other available antioxidants for the therapeutic strategy of Alzheimer diseases (AD) because of its protective activity against amyloid‐beta (Ab1‐42) accumulation, low toxicity effect, and readly passage through the blood‐brain barrier. The beneficial role of melatonin supplementation on...
Citation: Tchekalarova, J.; Todorov, P.; Stoyanova, T.; Atanasova, M. Comparative Analysis of Anticonvulsant Activity of Trans and Cis 5,5-Diphenylhydantoin Schiff Bases. Int. Abstract: Recently, the four 5,5-diphenylhydantoin Schiff bases, possessing different aromatic species (SB1-Ph, SB2-Ph, SB3-Ph and SB4-Ph) were synthesized, characterized, an...
Exogenous treatment during pregnancy with steroid hormones (estrogens, androgens, or glucocorticoids) affects the development of the fetus and the sexually mature generation. In clinical practice, the hormone progesterone is used therapeutically in programmes for assisted reproduction, infertility treatment, threatened abortion and premature birth....
Citation: Tchekalarova, J.; Todorov, P.; Rangelov, M.; Stoyanova, T.; Todorova, N. Additive Anticonvulsant Profile and Molecular Docking Analysis of 5,5-Diphenylhydantoin Schiff Bases and Phenytoin. Biomedicines 2023, 11, 2912. https://doi. Abstract: Four 5,5-diphenylhydantoin Schiff bases possessing different aromatic species (SB1-SB4) were recent...
Two series of new VV‐hemorphin‐5 analogs with structures Val–Val–Tyr–Xxx–Trp–Thr–Gln–NH 2 and Adam–Val–Val–Tyr–Xxx–Trp–Thr–Gln–NH 2 , where Xxx is Ac5c (1‐aminocyclopentane‐1‐carboxylic acid), Ac6c (1‐aminocyclohexane‐1‐carboxylic acid), Ac7c (1‐aminocycloheptane‐1‐carboxylic acid), and Adam is the low‐molecular‐weight lipophilic adamantyl building...
Melatonin deficiency caused by a prolonged light regime leads to a disturbance in the circadian rhythmicity of a number of physiological and biochemical parameters, including disruption of the synchronizing role of the hormone on endocrine and metabolic functions in the body. The aim of the present study was to explore the sex-dependent consequence...
Endothelial cells are constantly exposed to environmental stress factors that, above a certain threshold, trigger cellular senescence and apoptosis. The altered vascular function affects new vessel formation and endothelial fitness, contributing to the progression of age-related diseases. This narrative review highlights the complex interplay betwe...
Spontaneously hypertensive rats (SHRs) are widely accepted for modeling essential hypertension and Attention deficit hyperactivity disorder (ADHD). However, data concerning central nervous system changes associated with behavioral responses of this strain and usage of Wistar Kyoto (WKY) rats as controls are confounding. The objective of the present...
Aging and neurodegenerative diseases share common hallmarks, including mitochondrial dysfunction and protein aggregation. Moreover, one of the major issues of the demographic crisis today is related to the progressive rise in costs for care and maintenance of the standard living condition of aged patients with neurodegenerative diseases. There is a...
Prenatal stress impairs cognitive function in rats, while Piromelatine treatment corrects memory decline in male rats with chronic mild stress. In the present study, we aimed to evaluate the effect of chronic treatment with the melatonin analogue Piromelatine on the associative and spatial hippocampus-dependent memory of male and female offspring w...
The endogenous hemorphins are bioactive peptides with activity on opioid receptors. They are extensively studied and summarized in numerous reviews. During the last decade, several research teams have synthesized, characterized, and pharmacologically evaluated synthetic hemorphin analogs containing unusual amino acids, D-amino acids, α-aminophospho...
Aging is a natural phenomenon that involves many biological changes, including behavioral responses, DNA damage, diminished protein regulation, and mitochondrial dysfunction. The pineal gland has a crucial role in the programming fertility, growth, aging and death of mammals via the released hormone melatonin. The present study aimed to ascertain t...
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 [...]
Age-related neurological complications are common and affect the quality of life. The present study was designed to investigate age-dependent changes in behavioral responses and the role of protective heat shock proteins (Hsp)s 70 and Hsp 90, which expression in the frontal cortex (FC) might be vulnerable to aging processes in rats. We report that...
Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobio-logical, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and und...
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...
Prenatal stress (PNS) impairs the circadian rhythm of the sleep/wake cycle. The melatonin (MT) analogue Piromelatine (Pir) was designed for the treatment of insomnia. The present study aimed to explore effects of Pir on circadian rhythmicity, motor activity, and sleep structure in male and female rats with a history of prenatal stress (PNS). In add...
Epilepsy is a widespread neurological disorder frequently associated with a lot of comorbidities. The present study aimed to evaluate the effects of the antiseizure medication topiramate (TPM) on spontaneous motor seizures, the pathogenesis of comorbid mood and cognitive impairments, hippocampal neuronal loss, and oxidative stress and inflammation...
Taking into consideration the latest reported beneficial anticolvusant effects of cannabidiol (CBD) and cannabiodiolic acid (CBDA) for clinical applications and the advantages of lipid nano-systems as carriers for targeted brain delivery, the aim of this study was set in direction of in vitro physico-chemical and biopharmaceutical characterization...
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 pr...
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 t...
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...
In the present study, the aim was to compare the role of melatonin deficiency on emotional status in two different models, chronic constant light (CCL) and pinealectomy in male Wistar rats. While the rats with pinealectomy (Pin) showed impulsive behaviour (increased motor activity and lack of anxiety), CCL-rats demonstrated higher anxiety in the el...
We synthesized a series of novel indole compounds containing aroylhydrazone moieties and evaluated them in mice to check their anticonvulsant activity. In the present study the most potent C3-modified derivative 3e, containing 2-furyl fragment was evaluated in kainate (KA)-induced status epilepticus (SE) and the consequences on oxidative stress and...
In the present study, a series of new analogues of both LVV- and VV-hemorphin-7 have been synthesized and characterized. They were modified at the N- and C-terminus with varied amino acids (Ile, D-Leu, D-Val, D-Phe) and enantiopure chiral S- and R- α-aminophosphonic acids ((dimethoxyphosphoryl)methyl)-valine and ((dimethoxyphosphoryl) methyl)-leuci...
Herein, the synthesis and characterization of some novel N-modified hybrid analogues of hemorphins containing a C-5 substituted hydantoin residue as potential anticonvulsants and blockade of sodium channels are presented. Their structure-property relationships have been highlighted by electrochemical and Fourier Transform Infrared Spectroscopy (FT-...
One of the pathological hallmarks of Alzheimer's disease (AD) associated with its progression that contributes to β-amyloid (Aβ) generation is oxidative stress (OS). Clinical data suggest that melatonin is a potent antioxidant that might be effective in the adjunctive therapy of this neurodegenerative disease. The present study aimed to explore the...
Ръководството за практически упражнения по физиология на човека е предназна-чено за студенти от втори курс на магистърската програма по медицина на Медицинския факултет, СУ „Св. Климент Охридски“. То включва теми за упражнения от одобрена учебна програма, които покриват голяма част от курса по физиология на човека и са организирани по следния начин...
Ръководството за практически упражнения по физиология на човека е предназна-чено за студенти от втори курс на магистърската програма по медицина на Медицинския факултет, СУ „Св. Климент Охридски“. То включва теми за упражнения от одобрена учебна програма, които покриват голяма част от курса по физиология на човека и са организирани по следния начин...
Recently, we reported that the atypical antidepressant agomelatine (Ago) exerted a beneficial impact on behavioral changes and concomitant neuropathological events in icvSTZ rat model of sporadic Alzheimer diseases (AD). In the present study, we aimed to explore the effect of Ago (40 mg/kg, i.p. for 30 days) on beta-amyloid (Aβ) metabolism in icvAβ...
Experimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological pr...
The prenatal stress (PNS) model in rodents can induce different abnormal responses that replicate the pathophysiology of depression. We applied this model to evaluate the efficacy of piromelatine (Pir), a novel melatonin analog developed for the treatment of insomnia, in male and female offspring. Adult PNS rats from both sexes showed comparable di...
Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflamma...
Aim/objective. When applied in pharmacological doses, the indole derivative melatonin exhibits neuroactive and neuroprotective effects. Indoles and their metabolites, such as kynurenine, are ligands of aryl hydrocarbon receptors (AhR). This study aimed to evaluate the antiepileptic and analgesic activity of melatonin and two synthetic melatonin der...
Depression, concomitant with epilepsy, may cause serious impairment in one’s quality of life, not limited to seizures. Investigations of biomarkers and new therapeutic approaches targeting comorbid depression in epilepsy have been in progress for the past decade. In the attempt to find the mechanisms underlying the development of depression in epil...
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-base...
Background:
Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induce...
Introduction: Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients.
Aim: The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus.
Materials and methods: Male Wis...
An increased risk of developing Alzheimer’s disease (AD) exists in patients with a history of depression. In the present study, we demonstrated that chronic agomelatine intraperitoneal treatment, at a dose of 40 mg/ kg for 21 days, starting one month after inducing AD by intracerebroventricular injection of amyloid-beta (Aβ) corrected anhedonia, de...
Call for Paper: [Int J Mol Sci – IF 4.556] Special Issue “Significance of Antioxidants on Aging and Neurodegeneration”
Based on the pharmacophore model of melatonin (MT 1) receptor, we recently synthesized a series of indole derivatives that showed anticonvulsant activity with low neurotoxicity and hepatotoxicity in rodents. In the present study, the three most potent C3-modified derivatives with hydrazine structure 3c, 3e, and 3f, with 2-chlorophenyl, 2-furyl, and...
The bicyclic sesquiterpene β-caryophyllene (BCP) has diverse biological activities, including antioxidant, anti-inflammatory, antidiabetic, and analgesic effects. This study evaluates anxiolytic, toxicity, and antioxidant effects of BCP using in vitro and in vivo test models. The anxiolytic effects were tested in Swiss albino mice (Mus musculus) by...
In the present study, several new analogues of hemorphin-4, modified with unnatural conformationally restricted amino acids followed the structure Aaa–Tyr–Xxx–Trp–Thr–NH2, where Aaa is the low-molecular-weight lipophilic adamantyl building block, and Xxx is Ac5c (1-aminocyclopentanecarboxylic acid) or Ac6c (1-aminocyclohexane carboxylic acid) was s...
Pinealectomy can cause a disturbance in emotional status and circadian rhythms of the endocrine and metabolic functions in the body. Endurance training is considered a part of the complex therapy of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we aimed to study the effect of endurance...
Herein, some new analogues of VV-hemorphin-7, modified at position 4 and 7 by the unnatural amino acids followed the structure Val-Val-Tyr-Xxx-Trp-Thr-Yyy-Arg-Phe-NH2, where Xxx is Ac5c (1-aminocyclopentanecarboxylic acid) or Ac6c (1-aminocyclohexane carboxylic acid) and Yyy is Dap (diaminopropanoic acid) or Dab (diaminobutanoic acid), were synthes...
Rationale
Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity.
Objectives
In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in...