TY  - JOUR
AU  - Martinović, Jelena
AU  - Samardžić, Janko
AU  - Zarić Kontić, Marina
AU  - Ivković, Sanja
AU  - Dacić, Sanja
AU  - Major, Tamara
AU  - Radosavljević, Milica
AU  - Svob Strac, Dubravka
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12975
AB  - Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.
T2  - Brain Sciences
T1  - Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus
VL  - 13
IS  - 12
SP  - 1707
DO  - 10.3390/brainsci13121707
ER  - 

@article{
author = "Martinović, Jelena and Samardžić, Janko and Zarić Kontić, Marina and Ivković, Sanja and Dacić, Sanja and Major, Tamara and Radosavljević, Milica and Svob Strac, Dubravka",
year = "2023",
abstract = "Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.",
journal = "Brain Sciences",
title = "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus",
volume = "13",
number = "12",
pages = "1707",
doi = "10.3390/brainsci13121707"
}

Martinović, J., Samardžić, J., Zarić Kontić, M., Ivković, S., Dacić, S., Major, T., Radosavljević, M.,& Svob Strac, D.. (2023). Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences, 13(12), 1707.
https://doi.org/10.3390/brainsci13121707

Martinović J, Samardžić J, Zarić Kontić M, Ivković S, Dacić S, Major T, Radosavljević M, Svob Strac D. Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences. 2023;13(12):1707.
doi:10.3390/brainsci13121707 .

Martinović, Jelena, Samardžić, Janko, Zarić Kontić, Marina, Ivković, Sanja, Dacić, Sanja, Major, Tamara, Radosavljević, Milica, Svob Strac, Dubravka, "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus" in Brain Sciences, 13, no. 12 (2023):1707,
https://doi.org/10.3390/brainsci13121707 . .

TY  - CONF
AU  - Martinović, Jelena
AU  - Zarić Kontić, Marina
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša
AU  - Grković, Ivana
AU  - Stojanović, Zoran
AU  - Drakulić, Dunja
AU  - Samardžić, Janko
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11047
AB  - Zaleplon, a member of Z-drugs, is a pyrazolopyrimidine hypnotic with sedative, anxiolytic, anticonvulsant and muscle relaxant properties. Zaleplon is approved for the short-term management of insomnia since acting as positive γ-aminobutyric acid (GABA) receptor allosteric modulator increases efficacy of inhibition on brain excitability. Importantly, for the proper functioning of the brain a balance between inhibitory (i.e., GABAergic) and excitatory (i.e., glutamatergic) system must be accomplished. This may be fulfilled by control of presynaptic elements (synthesis or degradation of glutamate and GABA neurotransmitters, their compartmentation, releasing and recycling) and regulation of expression and function of glutamate and GABA receptors. Hence, we aimed to investigate effects of prolonged zaleplon treatment on the expression of proteins involved in the gabaergic and glutamatergic signalization in the hippocampus of adult male Wistar rats. Five-day intraperitoneal administration increased level of components of GABAergic signalization (glutamate decarboxylase 67-GAD67, vesicular GABA transporter-VGAT and α1 subunit of GABA receptor-GABAAα1). This was accompanied by increased level of glutamatergic components (vesicular glutamate transporter 1-vGlut1 and subunits of glutamate N-Methyl-d-aspartate receptor-NMDAR, namely NR1, NR2A, NR2B), which clearly indicate maintenance of balance between main inhibitory and excitatory neurotransmitters. Given the importance of equilibrium of these systems for neuronal excitability, synaptic plasticity and cognitive functions, as well as its involvement in the mood, feeding behavior, reproductive functions, pain sensitivity, aging, etc., the current and prospective pharmaceuticals increasingly rely on GABA/glutamate balance
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats
SP  - 59
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11047
ER  - 

@conference{
author = "Martinović, Jelena and Zarić Kontić, Marina and Guševac Stojanović, Ivana and Mitrović, Nataša and Grković, Ivana and Stojanović, Zoran and Drakulić, Dunja and Samardžić, Janko",
year = "2023",
abstract = "Zaleplon, a member of Z-drugs, is a pyrazolopyrimidine hypnotic with sedative, anxiolytic, anticonvulsant and muscle relaxant properties. Zaleplon is approved for the short-term management of insomnia since acting as positive γ-aminobutyric acid (GABA) receptor allosteric modulator increases efficacy of inhibition on brain excitability. Importantly, for the proper functioning of the brain a balance between inhibitory (i.e., GABAergic) and excitatory (i.e., glutamatergic) system must be accomplished. This may be fulfilled by control of presynaptic elements (synthesis or degradation of glutamate and GABA neurotransmitters, their compartmentation, releasing and recycling) and regulation of expression and function of glutamate and GABA receptors. Hence, we aimed to investigate effects of prolonged zaleplon treatment on the expression of proteins involved in the gabaergic and glutamatergic signalization in the hippocampus of adult male Wistar rats. Five-day intraperitoneal administration increased level of components of GABAergic signalization (glutamate decarboxylase 67-GAD67, vesicular GABA transporter-VGAT and α1 subunit of GABA receptor-GABAAα1). This was accompanied by increased level of glutamatergic components (vesicular glutamate transporter 1-vGlut1 and subunits of glutamate N-Methyl-d-aspartate receptor-NMDAR, namely NR1, NR2A, NR2B), which clearly indicate maintenance of balance between main inhibitory and excitatory neurotransmitters. Given the importance of equilibrium of these systems for neuronal excitability, synaptic plasticity and cognitive functions, as well as its involvement in the mood, feeding behavior, reproductive functions, pain sensitivity, aging, etc., the current and prospective pharmaceuticals increasingly rely on GABA/glutamate balance",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats",
pages = "59",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11047"
}

Martinović, J., Zarić Kontić, M., Guševac Stojanović, I., Mitrović, N., Grković, I., Stojanović, Z., Drakulić, D.,& Samardžić, J.. (2023). Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 59.
https://hdl.handle.net/21.15107/rcub_vinar_11047

Martinović J, Zarić Kontić M, Guševac Stojanović I, Mitrović N, Grković I, Stojanović Z, Drakulić D, Samardžić J. Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:59.
https://hdl.handle.net/21.15107/rcub_vinar_11047 .

Martinović, Jelena, Zarić Kontić, Marina, Guševac Stojanović, Ivana, Mitrović, Nataša, Grković, Ivana, Stojanović, Zoran, Drakulić, Dunja, Samardžić, Janko, "Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):59,
https://hdl.handle.net/21.15107/rcub_vinar_11047 .