Delayed BDNF alterations in the prefrontal cortex of rats exposed to prenatal stress: preventive effect of lurasidone treatment during adolescence.
Psychiatric diseases may often represent the consequence of exposure to adverse events early in life. Accordingly, exposure to stress during gestation in rats has a strong impact on development and can cause long-term abnormalities in adult behavior. Considering that neuronal plasticity has emerged as a major vulnerability element in psychiatric disorders, we investigated the postnatal developmental profile of Brain-Derived Neurotrophic Factor expression (BDNF), an important mediator for long-term functional deterioration associated to mental illness, in male and female rats following exposure to prenatal stress (PNS). Since we found that the majority of alterations became fully manifest at early adulthood, we tried to prevent these abnormalities with an early pharmacological intervention. To address this point, we treated rats during adolescence with the multi-receptor antipsychotic lurasidone, which was proven to be effective in animal models of schizophrenia. Interestingly, we show that lurasidone treatment was able to prevent the reduction of BDNF expression in adult rats that were exposed to PNS. Collectively, our results provide further support to the notion that exposure to early life stress has a negative impact on neuronal plasticity and that pharmacological intervention during critical time windows may prove effective in preventing neuroplastic dysfunction, leading to long-term beneficial effects on brain function.
Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy.
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Luoni
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, I-00161 Rome, Italy.
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Berry
Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy.
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Calabrese
IRCCS "Centro San Giovanni di Dio" Fatebenefratelli, I-25134 Brescia, Italy.
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Capoccia
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, I-00161 Rome, Italy.
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Bellisario
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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Gass
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, I-00161 Rome, Italy.
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Cirulli
Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy. Electronic address: M.Riva@unimi.it.
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Riva
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D054833:Isoindoles / Q000494:pharmacology*; D000069056:Lurasidone Hydrochloride; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D054833:Isoindoles; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride
BDNF; Gestational stress; Lurasidone; Postnatal development