The PPARα agonist fenofibrate attenuates disruption of dopamine function in a maternal immune activation rat model of schizophrenia.
CNS Neurosci Ther
; 25(5): 549-561, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30461214
ABSTRACT
AIMS:
Prenatal maternal immune activation (MIA) is associated with a risk to develop schizophrenia and affects dopamine systems in the ventral tegmental area (VTA), key region in the neurobiology of psychoses. Considering the well-described sex differences in schizophrenia, we investigated whether sex affects MIA impact on dopamine system and on schizophrenia-related behavioral phenotype. Furthermore, considering peroxisome proliferator-activated receptor-α (PPARα) expression in the CNS as well as its anti-inflammatory and neuroprotective properties, we tested if PPARα activation by prenatal treatment with a clinically available fibrate (fenofibrate) may mitigate MIA-related effects.METHODS:
We induced MIA in rat dams with polyriboinosinic-polyribocytidylic acid (Poly IC) and assessed prepulse inhibition and dopamine neuron activity in the VTA by means of electrophysiological recordings in male and female preweaned and adult offspring.RESULTS:
Poly IC-treated males displayed prepulse inhibition deficits, reduced number and firing rate of VTA dopamine neurons, and paired-pulse facilitation of inhibitory and excitatory synapses. Prenatal fenofibrate administration attenuated detrimental effects induced by MIA on both the schizophrenia-like behavioral phenotype and dopamine transmission in male offspring.CONCLUSION:
Our study confirms previous evidence that females are less susceptible to MIA and highlights PPARα as a potential target for treatments in schizophrenia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complicações na Gravidez
/
Efeitos Tardios da Exposição Pré-Natal
/
Fenofibrato
/
Esquizofrenia
/
Dopamina
/
Substâncias Protetoras
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
CNS Neurosci Ther
Assunto da revista:
NEUROLOGIA
/
TERAPEUTICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália