Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like
Alterations in the Neurodevelopmental MAM Model of
Schizophrenia

J 2022

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

ŠTARK, Tibor, Fabio Arturo IANNOTI, Serena DI MARTINO, Martina DI BARTOLOMEO, Jana RUDÁ et. al.

Basic information

Original name

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

Name in Czech

Časná blokáda CB1 receptorů normalizuje schizofrenii-podobné alterace v neurovývojovém MAM modelu schizofrenie

Authors

ŠTARK, Tibor (703 Slovakia, belonging to the institution), Fabio Arturo IANNOTI (380 Italy), Serena DI MARTINO (380 Italy), Martina DI BARTOLOMEO (380 Italy), Jana RUDÁ (203 Czech Republic, guarantor, belonging to the institution), Fabiana PISCITELLI (380 Italy), Carsten T. WOTJAK (276 Germany), Claudio D’ADDARIO (380 Italy), Filippo DRAGO (380 Italy), Vincenzo DI MARZO (380 Italy) and Vincenzo MICALE (380 Italy)

Edition

Biomolecules, Basel, Switzerland, MDPI AG, 2022, 2218-273X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.500

RIV identification code

RIV/00216224:14110/22:00125204

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/biom12010108

UT WoS

000758489500001

Keywords in English

MAM model; schizophrenia; AM251; endocannabinoid system; 2-arachidonoylglycerol (2-AG); cannabinoid CB1 receptor

Abstract

V originále

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.

Links

MUNI/A/1440/2021, interní kód MU

Name: Preklinický a klinický výzkum Farmakologického ústavu v oblasti farmakokinetiky, neurobiologie závislostí a personalizované farmakoterapie v onkologii (Acronym: Farm-Pre-Klin)

Investor: Masaryk University

3SGA5789, interní kód MU

Name: PRECIPITATION OF SCHIZOPHRENIA-LIKE PHENOTYPE BY PRENATAL INFLUENCES: ASSESSING THE ROLE OF THE ENDOCANNABINOID SYSTEM (Acronym: ncRNAPain)

Investor: South-Moravian Region, Incoming grants

Citovat

ŠTARK, Tibor, Fabio Arturo IANNOTI, Serena DI MARTINO, Martina DI BARTOLOMEO, Jana RUDÁ, Fabiana PISCITELLI, Carsten T. WOTJAK, Claudio D’ADDARIO, Filippo DRAGO, Vincenzo DI MARZO and Vincenzo MICALE. Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia. Biomolecules. Basel, Switzerland: MDPI AG, 2022, vol. 12, No 1, p. 1-15. ISSN 2218-273X. Available from: https://dx.doi.org/10.3390/biom12010108.

@article{1824340,
   author = {Štark, Tibor and Iannoti, Fabio Arturo and Di Martino, Serena and Di Bartolomeo, Martina and Rudá, Jana and Piscitelli, Fabiana and Wotjak, Carsten T. and D’Addario, Claudio and Drago, Filippo and Di Marzo, Vincenzo and Micale, Vincenzo},
   article_location = {Basel, Switzerland},
   article_number = {1},
   doi = {http://dx.doi.org/10.3390/biom12010108},
   keywords = {MAM model; schizophrenia; AM251; endocannabinoid system; 2-arachidonoylglycerol (2-AG); cannabinoid CB1 receptor},
   language = {eng},
   issn = {2218-273X},
   journal = {Biomolecules},
   title = {Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia},
   url = {https://www.mdpi.com/2218-273X/12/1/108},
   volume = {12},
   year = {2022}
}

TY  - JOUR
ID  - 1824340
AU  - Štark, Tibor - Iannoti, Fabio Arturo - Di Martino, Serena - Di Bartolomeo, Martina - Rudá, Jana - Piscitelli, Fabiana - Wotjak, Carsten T. - D’Addario, Claudio - Drago, Filippo - Di Marzo, Vincenzo - Micale, Vincenzo
PY  - 2022
TI  - Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia
JF  - Biomolecules
VL  - 12
IS  - 1
SP  - 1-15
EP  - 1-15
PB  - MDPI AG
SN  - 2218273X
KW  - MAM model
KW  - schizophrenia
KW  - AM251
KW  - endocannabinoid system
KW  - 2-arachidonoylglycerol (2-AG)
KW  - cannabinoid CB1 receptor
UR  - https://www.mdpi.com/2218-273X/12/1/108
N2  - In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.
ER  -

ŠTARK, Tibor, Fabio Arturo IANNOTI, Serena DI MARTINO, Martina DI BARTOLOMEO, Jana RUDÁ, Fabiana PISCITELLI, Carsten T. WOTJAK, Claudio D’ADDARIO, Filippo DRAGO, Vincenzo DI MARZO and Vincenzo MICALE. Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia. \textit{Biomolecules}. Basel, Switzerland: MDPI AG, 2022, vol.~12, No~1, p.~1-15. ISSN~2218-273X. Available from: https://dx.doi.org/10.3390/biom12010108.

Detailed Information on Publication Record