Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus
Аутори
Martinović, JelenaSamardžić, Janko
Zarić Kontić, Marina
Ivković, Sanja
Dacić, Sanja
Major, Tamara
Radosavljević, Milica
Švob Štrac, Dubravka
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 th...e 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.
Кључне речи:
rats / GABA / adenosine / glutamate / hippocampus / Z drugs / zaleplonИзвор:
Brain Sciences, 2023, 13, 12Издавач:
- MDPI
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-MESTD-inst-2020-200017)
DOI: 10.3390/brainsci13121707
ISSN: 2076-3425
PubMed: 38137155
WoS: 001130643700001
Scopus: 2-s2.0-85180460356
Институција/група
PharmacyTY - JOUR AU - Martinović, Jelena AU - Samardžić, Janko AU - Zarić Kontić, Marina AU - Ivković, Sanja AU - Dacić, Sanja AU - Major, Tamara AU - Radosavljević, Milica AU - Švob Štrac, Dubravka PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5407 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. PB - MDPI 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 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 Švob Štrac, 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.", publisher = "MDPI", 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", doi = "10.3390/brainsci13121707" }
Martinović, J., Samardžić, J., Zarić Kontić, M., Ivković, S., Dacić, S., Major, T., Radosavljević, M.,& Švob Štrac, D.. (2023). Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences MDPI., 13(12). https://doi.org/10.3390/brainsci13121707
Martinović J, Samardžić J, Zarić Kontić M, Ivković S, Dacić S, Major T, Radosavljević M, Švob Štrac 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). doi:10.3390/brainsci13121707 .
Martinović, Jelena, Samardžić, Janko, Zarić Kontić, Marina, Ivković, Sanja, Dacić, Sanja, Major, Tamara, Radosavljević, Milica, Švob Štrac, 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), https://doi.org/10.3390/brainsci13121707 . .