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Auteur Amaicha Mara DEPINO |
Documents disponibles écrits par cet auteur (2)
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Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism / Luciana LUCCHINA in Autism Research, 7-2 (April 2014)
[article]
Titre : Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism Type de document : Texte imprimé et/ou numérique Auteurs : Luciana LUCCHINA, Auteur ; Amaicha Mara DEPINO, Auteur Article en page(s) : p.273-289 Mots-clés : valproic acid cytokines microglia astroglia hypothalamus–pituitary–adrenal axis behavior Index. décimale : PER Périodiques Résumé : Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600?mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism-related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. En ligne : http://dx.doi.org/10.1002/aur.1338 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=230
in Autism Research > 7-2 (April 2014) . - p.273-289[article] Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism [Texte imprimé et/ou numérique] / Luciana LUCCHINA, Auteur ; Amaicha Mara DEPINO, Auteur . - p.273-289.
in Autism Research > 7-2 (April 2014) . - p.273-289
Mots-clés : valproic acid cytokines microglia astroglia hypothalamus–pituitary–adrenal axis behavior Index. décimale : PER Périodiques Résumé : Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600?mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism-related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. En ligne : http://dx.doi.org/10.1002/aur.1338 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=230 Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment / M. CAMPOLONGO in Molecular Autism, 9 (2018)
[article]
Titre : Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment Type de document : Texte imprimé et/ou numérique Auteurs : M. CAMPOLONGO, Auteur ; N. KAZLAUSKAS, Auteur ; G. FALASCO, Auteur ; L. URRUTIA, Auteur ; N. SALGUEIRO, Auteur ; C. HOCHT, Auteur ; Amaicha Mara DEPINO, Auteur Article en page(s) : 36p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/etiology/therapy Brain/diagnostic imaging Female Male Mice Pregnancy Prenatal Exposure Delayed Effects/drug therapy/etiology Social Behavior Socioenvironmental Therapy/methods Valproic Acid/administration & dosage/toxicity Autism spectrum disorder Dopamine Piriform cortex Sociability Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown. By analyzing the effects of early social stimulation on ASD-related behavior in the mouse, we aimed to identify brain structures that contribute to these behaviors. Methods: We injected pregnant mice with 600-mg/kg valproic acid (VPA) or saline (SAL) at gestational day 12.5 and evaluated the effect of weaning their offspring in cages containing only VPA animals, only SAL animals, or mixed. We analyzed juvenile play at PD21 and performed a battery of behavioral tests in adulthood. We then used preclinical PET imaging for an unbiased analysis of the whole brain of these mice and studied the function of the piriform cortex by c-Fos immunoreactivity and HPLC. Results: Compared to control animals, VPA-exposed animals play less as juveniles and exhibit a lower frequency of social interaction in adulthood when reared with other VPA mice. In addition, these animals were less likely to investigate social odors in the habituation/dishabituation olfactory test. However, when VPA animals were weaned with control animals, these behavioral alterations were not observed. Interestingly, repetitive behaviors and depression-related behaviors were not affected by social enrichment. We also found that VPA animals present high levels of glucose metabolism bilaterally in the piriform cortex (Pir), a region known to be involved in social behaviors. Moreover, we found alterations in the somatosensory, motor, and insular cortices. Remarkably, these effects were mostly reversed after social stimulation. To evaluate if changes in glucose metabolism in the Pir correlated with changes in neuronal activity, we measured c-Fos immunoreactivity in the Pir and found it increased in animals prenatally exposed to VPA. We further found increased dopamine turnover in the Pir. Both alterations were largely reversed by social enrichment. Conclusions: We show that early social enrichment can specifically rescue social deficits in a mouse model of ASD. Our results identified the Pir as a structure affected by VPA-exposure and social enrichment, suggesting that it could be a key component of the social brain circuitry. En ligne : https://dx.doi.org/10.1186/s13229-018-0221-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 36p.[article] Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment [Texte imprimé et/ou numérique] / M. CAMPOLONGO, Auteur ; N. KAZLAUSKAS, Auteur ; G. FALASCO, Auteur ; L. URRUTIA, Auteur ; N. SALGUEIRO, Auteur ; C. HOCHT, Auteur ; Amaicha Mara DEPINO, Auteur . - 36p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 36p.
Mots-clés : Animals Autism Spectrum Disorder/etiology/therapy Brain/diagnostic imaging Female Male Mice Pregnancy Prenatal Exposure Delayed Effects/drug therapy/etiology Social Behavior Socioenvironmental Therapy/methods Valproic Acid/administration & dosage/toxicity Autism spectrum disorder Dopamine Piriform cortex Sociability Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown. By analyzing the effects of early social stimulation on ASD-related behavior in the mouse, we aimed to identify brain structures that contribute to these behaviors. Methods: We injected pregnant mice with 600-mg/kg valproic acid (VPA) or saline (SAL) at gestational day 12.5 and evaluated the effect of weaning their offspring in cages containing only VPA animals, only SAL animals, or mixed. We analyzed juvenile play at PD21 and performed a battery of behavioral tests in adulthood. We then used preclinical PET imaging for an unbiased analysis of the whole brain of these mice and studied the function of the piriform cortex by c-Fos immunoreactivity and HPLC. Results: Compared to control animals, VPA-exposed animals play less as juveniles and exhibit a lower frequency of social interaction in adulthood when reared with other VPA mice. In addition, these animals were less likely to investigate social odors in the habituation/dishabituation olfactory test. However, when VPA animals were weaned with control animals, these behavioral alterations were not observed. Interestingly, repetitive behaviors and depression-related behaviors were not affected by social enrichment. We also found that VPA animals present high levels of glucose metabolism bilaterally in the piriform cortex (Pir), a region known to be involved in social behaviors. Moreover, we found alterations in the somatosensory, motor, and insular cortices. Remarkably, these effects were mostly reversed after social stimulation. To evaluate if changes in glucose metabolism in the Pir correlated with changes in neuronal activity, we measured c-Fos immunoreactivity in the Pir and found it increased in animals prenatally exposed to VPA. We further found increased dopamine turnover in the Pir. Both alterations were largely reversed by social enrichment. Conclusions: We show that early social enrichment can specifically rescue social deficits in a mouse model of ASD. Our results identified the Pir as a structure affected by VPA-exposure and social enrichment, suggesting that it could be a key component of the social brain circuitry. En ligne : https://dx.doi.org/10.1186/s13229-018-0221-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371