Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence
Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for centr...
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MDPI AG
2022-01-01
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| author | Balaji Gouda Sukesh Narayan Sinha Meram Chalamaiah Validandi Vakdevi Patangay Shashikala Bantal Veeresh Venkata Mullapudi Surekha Vasudev Kasturi Naveen Kumar Boiroju |
| author_facet | Balaji Gouda Sukesh Narayan Sinha Meram Chalamaiah Validandi Vakdevi Patangay Shashikala Bantal Veeresh Venkata Mullapudi Surekha Vasudev Kasturi Naveen Kumar Boiroju |
| author_sort | Balaji Gouda |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females. |
| first_indexed | 2024-03-10T01:53:49Z |
| format | Article |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T01:53:49Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Biology |
| spelling | doaj.art-3ab56c15f6044603a96ba1933420e5612023-11-23T13:00:50ZengMDPI AGBiology2079-77372022-01-011117910.3390/biology11010079Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker EvidenceBalaji Gouda0Sukesh Narayan Sinha1Meram Chalamaiah2Validandi Vakdevi3Patangay Shashikala4Bantal Veeresh5Venkata Mullapudi Surekha6Vasudev Kasturi7Naveen Kumar Boiroju8Division of Food Safety, Indian Council of Medical Research, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, IndiaDivision of Food Safety, Indian Council of Medical Research, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, IndiaDrug Safety Division, Indian Council of Medical Research, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, IndiaDivision of Food Safety, Indian Council of Medical Research, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, IndiaDepartment of Pharmacy, University College of Technology, Osmania University, Hyderabad 500027, IndiaDepartment of Pharmacology, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad 500028, IndiaDivision of Pathology and Microbiology, Indian Council of Medical Research, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, IndiaDivision of Food Safety, Indian Council of Medical Research, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, IndiaDivision of Biostatistics, Indian Council of Medical Research, National Institute of Nutrition, Tarnaka, Hyderabad 500007, IndiaAutism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females.https://www.mdpi.com/2079-7737/11/1/79autism spectrum disorderBALB/c micevalproic acidbrain histologyscanning electron microscopy5-HT2A receptor protein |
| spellingShingle | Balaji Gouda Sukesh Narayan Sinha Meram Chalamaiah Validandi Vakdevi Patangay Shashikala Bantal Veeresh Venkata Mullapudi Surekha Vasudev Kasturi Naveen Kumar Boiroju Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence Biology autism spectrum disorder BALB/c mice valproic acid brain histology scanning electron microscopy 5-HT2A receptor protein |
| title | Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence |
| title_full | Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence |
| title_fullStr | Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence |
| title_full_unstemmed | Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence |
| title_short | Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence |
| title_sort | sex differences in animal models of sodium valproate induced autism in postnatal balb c mice whole brain histoarchitecture and 5 ht2a receptor biomarker evidence |
| topic | autism spectrum disorder BALB/c mice valproic acid brain histology scanning electron microscopy 5-HT2A receptor protein |
| url | https://www.mdpi.com/2079-7737/11/1/79 |
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