Ultrasonic vocalization phenotypes in the Ts65Dn and Dp(16)1Yey mouse models of Down syndrome

Glass, Tiffany J.; Lenell, Charles; Fisher, Erin H.; Yang, Qiuyu; Connor, Nadine P.

doi:10.1016/j.physbeh.2023.114323

Cited by 2 publications

(1 citation statement)

References 80 publications

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“…We therefore chose to measure the pups’ behavioral and social responses on P7 and P8 (before eye opening), when the weight difference is smaller. Our results suggest that early social communication is impaired in Dp(16)1Yey pups, previously demonstrated at 5 months of age [ 25 ]. This impairment might be related to neurodevelopmental disorders [ 26 ], although we cannot rule out an influence of poor olfaction or low locomotor activity.…”

Section: Discussionsupporting

confidence: 74%

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Moreau,

Dard,

Madani

et al. 2024

Cell. Mol. Life Sci.

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Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

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Section: Discussionsupporting

confidence: 74%

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Moreau,

Dard,

Madani

et al. 2024

Cell. Mol. Life Sci.

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Prepartum bumetanide treatment reverses altered neonatal social communication but nonspecifically reduces postpubertal social behavior in a mouse model of fragile X syndrome

Sakamoto,

Takano,

Shimoyama

et al. 2024

Genomic Psychiatry

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Fragile X syndrome is caused by monogenic silencing of the FMR1 gene and is characterized by high rates of autism spectrum disorder. A previous study demonstrated that prepartum administration of bumetanide, a chloride transporter blocker, normalized neonatal vocalization in non-congenic Fmr1 knockout (KO) pups. However, the genuine contribution of Fmr1 deletion to this phenotype in a congenic Fmr1 KO mouse model and the long-lasting effect of prepartum bumetanide administration on postpubertal social interaction remains unclear. The current study aimed to determine the impact of prepartum bumetanide administration on vocalization at postnatal day 7 and social interaction at 6 and 8 weeks of age in a congenic Fmr1 KO mouse model in which the genetic backgrounds were homogeneous between KO and wild-type (WT) littermates. Moreover, we applied a computational analytical algorithm and determined predictive variables of neonatal vocalization for postpubertal social interaction. Our data showed that (1) KO mice exhibited altered numbers and sequences of distinct call types during neonatal vocalization and reduced social interaction at 6 weeks, (2) select sets of neonatal vocalization variables predicted postpubertal social interaction levels, and (3) bumetanide restored neonatal vocalization in KO pups but nonspecifically reduced social interaction in WT and KO mice at 6 weeks. These data indicate that Fmr1 deletion selectively impacts distinct elements of neonatal vocalization and postpubertal social interaction. Additionally, bumetanide selectively restores neonatal vocalization but has a transient nonspecific negative impact on subsequent postpubertal social interaction.

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Ultrasonic vocalization phenotypes in the Ts65Dn and Dp(16)1Yey mouse models of Down syndrome

Cited by 2 publications

References 80 publications

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Prepartum bumetanide treatment reverses altered neonatal social communication but nonspecifically reduces postpubertal social behavior in a mouse model of fragile X syndrome

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