Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism
Abstract Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experiment...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-04-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-024-02905-z |
| _version_ | 1797199227650048000 |
|---|---|
| author | Maria Bove Maria Adelaide Palmieri Martina Santoro Lisa Pia Agosti Silvana Gaetani Adele Romano Stefania Dimonte Giuseppe Costantino Vladyslav Sikora Paolo Tucci Stefania Schiavone Maria Grazia Morgese Luigia Trabace |
| author_facet | Maria Bove Maria Adelaide Palmieri Martina Santoro Lisa Pia Agosti Silvana Gaetani Adele Romano Stefania Dimonte Giuseppe Costantino Vladyslav Sikora Paolo Tucci Stefania Schiavone Maria Grazia Morgese Luigia Trabace |
| author_sort | Maria Bove |
| collection | DOAJ |
| description | Abstract Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala. |
| first_indexed | 2024-04-24T07:12:24Z |
| format | Article |
| id | doaj.art-efab544c43934ab29813574435abf3a8 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-24T07:12:24Z |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-efab544c43934ab29813574435abf3a82024-04-21T11:31:11ZengNature Publishing GroupTranslational Psychiatry2158-31882024-04-0114111010.1038/s41398-024-02905-zAmygdalar neurotransmission alterations in the BTBR mice model of idiopathic autismMaria Bove0Maria Adelaide Palmieri1Martina Santoro2Lisa Pia Agosti3Silvana Gaetani4Adele Romano5Stefania Dimonte6Giuseppe Costantino7Vladyslav Sikora8Paolo Tucci9Stefania Schiavone10Maria Grazia Morgese11Luigia Trabace12Department of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of RomeDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of RomeDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of RomeDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaDepartment of Clinical and Experimental Medicine, University of FoggiaAbstract Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.https://doi.org/10.1038/s41398-024-02905-z |
| spellingShingle | Maria Bove Maria Adelaide Palmieri Martina Santoro Lisa Pia Agosti Silvana Gaetani Adele Romano Stefania Dimonte Giuseppe Costantino Vladyslav Sikora Paolo Tucci Stefania Schiavone Maria Grazia Morgese Luigia Trabace Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism Translational Psychiatry |
| title | Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism |
| title_full | Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism |
| title_fullStr | Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism |
| title_full_unstemmed | Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism |
| title_short | Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism |
| title_sort | amygdalar neurotransmission alterations in the btbr mice model of idiopathic autism |
| url | https://doi.org/10.1038/s41398-024-02905-z |
| work_keys_str_mv | AT mariabove amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT mariaadelaidepalmieri amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT martinasantoro amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT lisapiaagosti amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT silvanagaetani amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT adeleromano amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT stefaniadimonte amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT giuseppecostantino amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT vladyslavsikora amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT paolotucci amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT stefaniaschiavone amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT mariagraziamorgese amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism AT luigiatrabace amygdalarneurotransmissionalterationsinthebtbrmicemodelofidiopathicautism |