Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA(A) and GABA(B) Receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00531146" target="_blank" >RIV/67985823:_____/20:00531146 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/20:10418456

Výsledek na webu

<a href="https://www.mdpi.com/1422-0067/21/9/3184" target="_blank" >https://www.mdpi.com/1422-0067/21/9/3184</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21093184" target="_blank" >10.3390/ijms21093184</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA(A) and GABA(B) Receptors

Popis výsledku v původním jazyce

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life, however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP, 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABA(A) receptor subunits (alpha 1, alpha 2, alpha 4, gamma 2, and delta) and the GABA(B) B2 subunit, and GABA(A), benzodiazepine, and GABA(B) receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the alpha 2 subunit was upregulated, whereas that of the delta subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the alpha 4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABA(A) receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABA(B) receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.

Název v anglickém jazyce

Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA(A) and GABA(B) Receptors

Popis výsledku anglicky

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life, however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP, 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABA(A) receptor subunits (alpha 1, alpha 2, alpha 4, gamma 2, and delta) and the GABA(B) B2 subunit, and GABA(A), benzodiazepine, and GABA(B) receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the alpha 2 subunit was upregulated, whereas that of the delta subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the alpha 4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABA(A) receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABA(B) receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA19-11931S" target="_blank" >GA19-11931S: Role miRNA ve vývoji glutamatergní a GABAergní signalizace po záchvatech v novorozeneckém období</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

20

Strana od-do

3184

Kód UT WoS článku

000535581700155

EID výsledku v databázi Scopus

2-s2.0-85084276453