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Adult hippocampal n...
Adult hippocampal neurogenesis and social behavioural deficits in the R451C Neuroligin3 mouse model of autism are reverted by the antidepressant fluoxetine
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- Gioia, Roberta (author)
- Sapienza University of Rome
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- Seri, Tommaso (author)
- Sapienza University of Rome
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- Diamanti, Tamara (author)
- Sapienza University of Rome
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- Fimmanò, Stefania (author)
- Sapienza University of Rome
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- Vitale, Marina (author)
- Sapienza University of Rome
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- Ahlenius, Henrik (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Stamceller, åldrande och neurodegeneration,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Stem Cells, Aging and Neurodegeneration,Lund University Research Groups
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- Kokaia, Zaal (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Skåne University Hospital
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- Tirone, Felice (author)
- CNR Istituto per le Tecnologie Applicate ai Beni Culturali (CNR-ITABC)
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- Micheli, Laura (author)
- CNR Istituto per le Tecnologie Applicate ai Beni Culturali (CNR-ITABC)
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- Biagioni, Stefano (author)
- Sapienza University of Rome
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- Lupo, Giuseppe (author)
- Sapienza University of Rome
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- Rinaldi, Arianna (author)
- Sapienza University of Rome
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- De Jaco, Antonella (author)
- Sapienza University of Rome
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- Cacci, Emanuele (author)
- Sapienza University of Rome
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(creator_code:org_t)
- 2023-01-09
- 2023
- English.
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 165:3, s. 318-333
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Abstract
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- Neuron generation persists throughout life in the hippocampus but is altered in animal models of neurological and neuropsychiatric diseases, suggesting that disease-associated decline in cognitive and emotional hippocampal-dependent behaviours might be functionally linked with dysregulation of postnatal neurogenesis. Depletion of the adult neural stem/progenitor cell (NSPCs) pool and neurogenic decline have been recently described in mice expressing synaptic susceptibility genes associated with autism spectrum disorder (ASDs). To gain further insight into mechanisms regulating neurogenesis in mice carrying mutations in synaptic genes related to monogenic ASDs, we used the R451C Neuroligin3 knock-in (Nlgn3 KI) mouse, which is characterized by structural brain abnormalities, deficits in synaptic functions and reduced sociability. We show that the number of adult-born neurons, but not the size of the NSPC pool, was reduced in the ventral dentate gyrus in knock-in mice. Notably, this neurogenic decline was rescued by daily injecting mice with 10 mg/Kg of the antidepressant fluoxetine for 20 consecutive days. Sustained treatment also improved KI mice's sociability and increased the number of c-Fos active adult-born neurons, compared with vehicle-injected KI mice. Our study uncovers neurogenesis-mediated alterations in the brain of R451C KI mouse, showing that the R451C Nlgn3 mutation leads to lasting, albeit pharmacologically reversible, changes in the brain, affecting neuron formation in the adult hippocampus. Our results suggest that fluoxetine can ameliorate social behaviour in KI mice, at least in part, by rescuing adult hippocampal neurogenesis, which may be relevant for the pharmacological treatment of ASDs. (Figure presented.).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Gioia, Roberta
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Seri, Tommaso
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Diamanti, Tamara
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Fimmanò, Stefani ...
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Vitale, Marina
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Ahlenius, Henrik
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show more...
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Kokaia, Zaal
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Tirone, Felice
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Micheli, Laura
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Biagioni, Stefan ...
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Lupo, Giuseppe
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Rinaldi, Arianna
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De Jaco, Antonel ...
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Cacci, Emanuele
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Neuro ...
- By the university
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Lund University