Decreased Microglia in <i>Pax2</i> Mutant Mice Leads to Impaired Learning and Memory

Lv, Na; Wang, Ying; Liu, Yongfeng; Tang, Jiaming; Lei, Qiang; Wang, Yizhuo; Wei, Huijie

doi:10.1021/acschemneuro.2c00352

Cited by 2 publications

(5 citation statements)

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“…Pax2 is one of the transcription factors expressed in many tissues, 8,19 and mutations in Pax2 lead to many diseases 9–11,20 . In previous studies, we found increased self‐grooming behavior and impaired spatial and memory abilities in Pax2 +/− mice 12,13 . In the present study, to investigate whether and how Pax2 ‐specific knockout in the nervous system affects the phenotypic behavior of mice, we assessed the behavioral phenotype, neural circuitry tracing, and RNA‐seq in the hippocampus of Nestin‐Pax2 mice and Pax2 flox mice.…”

Section: Discussionmentioning

confidence: 87%

“…[9][10][11]20 In previous studies, we found increased self-grooming behavior and impaired spatial and memory abilities in Pax2 +/− mice. 12,13 In the present study, to investigate Here, we identified the behavioral phenotypes of Nestin-Pax2 mice. We observed increased RRBs in both lower-order and higherorder.…”

Section: Discussionmentioning

confidence: 99%

“… 9 , 10 , 11 , 20 In previous studies, we found increased self‐grooming behavior and impaired spatial and memory abilities in Pax2 +/− mice. 12 , 13 In the present study, to investigate whether and how Pax2 ‐specific knockout in the nervous system affects the phenotypic behavior of mice, we assessed the behavioral phenotype, neural circuitry tracing, and RNA‐seq in the hippocampus of Nestin‐Pax2 mice and Pax2 flox mice. The results show increased RRBs in Nestin‐Pax2 mice, alterations in the mPFC → CA1/BLA neural circuitry, and deficits of IGFBP2 in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we investigated the behavioral phenotype and possible underlying mechanism in Pax2 heterozygous gene knockout mice ( Pax2 +/− mice). The Pax2 +/− mice showed increased self‐grooming behavior and impaired spatial and memory abilities, which were attributed to microglia‐mediated synaptic dysfunction 12,13 . Due to the limitations of heterozygous gene knockout, we generated Pax2 nervous system‐specific knockout mice ( Nestin‐Pax2 ) to reduce the impact of other systems on the research.…”

Section: Introductionmentioning

confidence: 99%

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Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors

Wang,

Tang

et al. 2023

CNS Neurosci Ther

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IntroductionRestricted repetitive behaviors (RRBs), which are associated with many different neurological and mental disorders, such as obsessive‐compulsive disorder (OCD) and autism, are patterns of behavior with little variation and little obvious function. Paired Box 2 (Pax2) is a transcription factor that is expressed in many systems, including the kidney and the central nervous system. The protein that is encoded by Pax2 has been implicated in the development of the nervous system and neurodevelopmental disorders. In our previous study, Pax2 heterozygous gene knockout mice (Pax2+/− mice) showed abnormally increased self‐grooming and impaired learning and memory abilities. However, it remains unclear which cell type is involved in this process. In this study, we deleted Pax2 only in the nervous system to determine the regulatory mechanism of Pax2 in RRBs.MethodsIn this study, Pax2 nervous system‐specific knockout mice (Nestin‐Pax2 mice) aged 6–8 weeks and Pax2 flox mice of the same age were recruited as the experimental group. Tamoxifen and vehicle were administered via intraperitoneal injection to induce Pax2 knockout after gene identification. Western blotting was used to detect Pax2 expression. After that, we assessed the general health of these two groups of mice. The self‐grooming test, marble burying test and T‐maze acquisition and reversal learning test were used to observe the lower‐order and higher‐order RRBs. The three‐chamber test, Y‐maze, and elevated plus‐maze were used to assess social ability, spatial memory ability, and anxiety. Neural circuitry tracing and transcriptome sequencing (RNA‐seq) were used to observe the abnormal neural circuitry, differentially expressed genes (DEGs) and signaling pathways affected by Pax2 gene knockout in the nervous system and the putative molecular mechanism.Results(1) The Nestin‐Pax2 mouse model was successfully constructed, and the Nestin‐Pax2 mice showed decreased expression of Pax2. (2) Nestin‐Pax2 mice showed increased self‐grooming behavior and impaired T‐maze reversal behavior compared with Pax2 flox mice. (3) An increased number of projection fibers can be found in the mPFC projecting to the CA1 and BLA, and a reduction in IGFBP2 can be found in the hippocampus of Nestin‐Pax2 mice.ConclusionThe results demonstrated that loss of Pax2 in the nervous system leads to restricted repetitive behaviors. The mechanism may be associated with impaired neural circuitry and a reduction in IGFBP2.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors

Wang,

Tang

et al. 2023

CNS Neurosci Ther

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“…Other differentially expressed genes in our data set, such as S-phase kinaseassociated protein 2 (BANY.1.2.g25897; skp2) [45,49], have been implicated in cognition function and neuronal growth in Alzheimer's studies using mice [88], as well as in eye development in D. melanogaster [89] (Fig 4). Paired box 2 (BANY.1.2.g21950; Pax2/sv), a member of the retinal determination gene network, is known to be primarily involved in eye/ photoreceptor development [90,91], but recent studies show that it also influences spatial learning in mice and autism spectrum disorders in humans and mice [92][93][94][95] (Fig 4).…”

Section: Discussionmentioning

confidence: 99%

Asynchronous temporal variance in learning behaviour and neural gene expression in a butterfly

Ter,

Westerman

2024

Preprint

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Mate preference learning, including imprinting-like learning, is pervasive across animal taxa, and can affect the selection and maintenance of certain phenotypes. However, not much is known about the temporal dynamics behind imprinting-like learning, or the genetic underpinnings underlying it. To uncover the temporal dynamics of imprinting-like learning, from both a behavioural and transcriptional perspective, we conducted learning and RNA-Seq time series using the butterfly Bicyclus anynana, a species where both sexes learn mate preferences. We exposed females to an unfamiliar, unpreferred male phenotype (4-spotted male) for five different exposure (training) periods, ranging from 30 minutes to three hours, and recorded their choice between the preferred, familiar male phenotype (2-spotted) and 4-spotted males in mate choice trials conducted two days after training. We also assessed differential gene expression of naive females and females exposed to trainer males for these same five exposure periods, to identify temporal patterns in gene expression associated with learning. While we found that the longest exposure had the strongest effect on preference learning, we did not observe a linear effect of exposure time on learning. We also show that the highest peak of differentially expressed genes (DEGs) was after one hour of exposure. While a number of genes were uniquely DE at each time point, one gene, associated with transcription initiation, was differentially expressed during learning across all five time points. We observed a similar decreasing trend in both gene expression and learned response after 1.5 hours of exposure, offering new insights to possible attention and forgetting mechanisms. Therefore, our results indicate that both gene expression and learning are temporally dynamic, and not linear through time. They also highlight the role of transcription in mate preference learning and memory formation in Lepidoptera, and illustrate that imprinting-like learning may exhibit similar molecular temporal dynamics as associative learning.

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Decreased Microglia in Pax2 Mutant Mice Leads to Impaired Learning and Memory

Cited by 2 publications

References 47 publications

Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors

Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors

Asynchronous temporal variance in learning behaviour and neural gene expression in a butterfly

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