scholarly journals Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders

2017 ◽  
Vol 23 (3) ◽  
pp. 544-555 ◽  
Author(s):  
N M Grissom ◽  
S E McKee ◽  
H Schoch ◽  
N Bowman ◽  
R Havekes ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Reward Learning ◽  
Natural Reward ◽  
Male Specific

scholarly journals Male-specific CREB signaling in the hippocampus controls spatial memory deficits in a mouse model of autism and intellectual disability

2018 ◽  
Author(s):  
Marta Zamarbide ◽  
Adele Mossa ◽  
Molly K. Wilkinson ◽  
Heather L. Pond ◽  
Adam W. Oaks ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Coiled Coil ◽  
Autism Spectrum ◽  
Behavioral Studies ◽  
Males And Females ◽  
Male Specific

ABSTRACTBackgroundThe prevalence of neurodevelopmental disorders is biased towards males with male: female ratios of 2:1 in intellectual disability (ID) and 4:1 in autism spectrum disorder (ASD). However, the molecular mechanisms of such bias remain unknown. While characterizing a mouse model for loss of the signaling scaffold coiled-coil and C2 domain containing 1A (CC2D1A), which is mutated in ID and ASD, we identified biochemical and behavioral differences between males and females, and explored whether CC2D1A controls male-specific intracellular signaling.MethodsCC2D1A is known to regulate phosphodiesterase 4D (PDE4D). We tested for activation PDE4D and downstream signaling molecules such as CREB in the hippocampus of Cc2d1a-deficient mice. We then performed behavioral studies in females to analyze learning and memory, social interactions, anxiety and hyperactivity. Finally, we targeted PDE4D activation with a PDE4D inhibitor to define how changes in PDE4D and CREB activity affect behavior in males and females.ResultsWe found that in Cc2d1a-deficient males PDE4D is hyperactive leading to a reduction in CREB signaling, but this molecular deficit is not present in females. Cc2d1a-deficient females only show impairment in novel object recognition, and no other cognitive and social deficits that have been found in males. Restoring PDE4D activity using an inhibitor rescues male-specific cognitive deficits, but has no effect on females.ConclusionsOur findings show that CC2D1A regulates intracellular signaling in a male-specific manner in the hippocampus leading to male-specific behavioral deficits. We propose that male-specific signaling mechanisms are involved in establishing sex bias in neurodevelopmental disorders.

Preeclampsia and Risk for Neurodevelopmental Disorders: Mouse Model Insights Into IL17 and Placental Function

2021 ◽  
Vol 89 (9) ◽  
pp. S65-S66
Author(s):  
Banu Gumusoglu ◽  
Akanksha Chilukuri ◽  
Sabrina Scroggins ◽  
Benjamin Hing ◽  
Jessica DeWitt ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Placental Function

scholarly journals Male-Specific cAMP Signaling in the Hippocampus Controls Spatial Memory Deficits in a Mouse Model of Autism and Intellectual Disability

2019 ◽  
Vol 85 (9) ◽  
pp. 760-768 ◽  
Author(s):  
Marta Zamarbide ◽  
Adele Mossa ◽  
Pablo Muñoz-Llancao ◽  
Molly K. Wilkinson ◽  
Heather L. Pond ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Spatial Memory ◽  
Memory Deficits ◽  
Camp Signaling ◽  
Male Specific

scholarly journals Developmental exposure to diesel exhaust upregulates transcription factor expression, decreases hippocampal neurogenesis, and alters cortical lamina organization: relevance to neurodevelopmental disorders

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Toby B. Cole ◽  
Yu-Chi Chang ◽  
Khoi Dao ◽  
Ray Daza ◽  
Robert Hevner ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Diesel Exhaust ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Hippocampal Neurogenesis ◽  
Behavioral Alterations ◽  
Developmental Exposure ◽  
Males And Females ◽  
Male Specific ◽  
Transcription Factor Expression

Abstract Background Exposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer’s disease (AD) or Parkinson’s disease (PD). Methods In the present study, C57BL/6 J mice were exposed to environmentally relevant levels (250+/−50 μg/m3) of diesel exhaust (DE) or filtered air (FA) during development (E0 to PND21). The expression of several transcription factors relevant for CNS development was assessed on PND3. To address possible mechanistic underpinnings of previously observed behavioral effects of DE exposure, adult neurogenesis in the hippocampus and laminar organization of neurons in the somatosensory cortex were analyzed on PND60. Results were analyzed separately for male and female mice. Results Developmental DE exposure caused a male-specific upregulation of Pax6, Tbr1, Tbr2, Sp1, and Creb1 on PND3. In contrast, in both males and females, Tbr2+ intermediate progenitor cells in the PND60 hippocampal dentate gyrus were decreased, as an indication of reduced adult neurogenesis. In the somatosensory region of the cerebral cortex, laminar distribution of Trb1, calbindin, and parvalbumin (but not of Ctip2 or Cux1) was altered by developmental DE exposure. Conclusions These results provide additional evidence to previous findings indicating the ability of developmental DE exposure to cause biochemical/molecular and behavioral alterations that may be involved in neurodevelopmental disorders such as ASD.

scholarly journals Impairments in sensory-motor gating and information processing in a mouse model of Ehmt1 haploinsufficiency

2020 ◽  
Vol 4 ◽  
pp. 239821282092864
Author(s):  
Brittany A Davis ◽  
François David ◽  
Ciara O’Regan ◽  
Manal A Adam ◽  
Adrian J Harwood ◽  
...  
Keyword(s):  
Information Processing ◽  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Auditory Evoked Potentials ◽  
Autism Spectrum ◽  
Oscillatory Activity ◽  
Kleefstra Syndrome ◽  
Sensory Motor ◽  
Processing Deficits ◽  
Information Processing Deficits

Regulators of chromatin dynamics and transcription are increasingly implicated in the aetiology of neurodevelopmental disorders. Haploinsufficiency of EHMT1, encoding a histone methyltransferase, is associated with several neurodevelopmental disorders, including Kleefstra syndrome, developmental delay and autism spectrum disorder. Using a mouse model of Ehmt1 haploinsufficiency ( Ehmt1D6Cre/+), we examined a number of brain and behavioural endophenotypes of relevance to neurodevelopmental disorders. Specifically, we show that Ehmt1D6Cre/+ mice have deficits in information processing, evidenced by abnormal sensory-motor gating, a complete absence of object recognition memory, and a reduced magnitude of auditory evoked potentials in both paired-pulse inhibition and mismatch negativity. The electrophysiological experiments show that differences in magnitude response to auditory stimulus were associated with marked reductions in total and evoked beta- and gamma-band oscillatory activity, as well as significant reductions in phase synchronisation. The pattern of electrophysiological deficits in Ehmt1D6Cre/+ matches those seen in control mice following administration of the selective NMDA-R antagonist, ketamine. This, coupled with reduction of Grin1 mRNA expression in Ehmt1D6Cre/+ hippocampus, suggests that Ehmt1 haploinsufficiency may lead to disruption in NMDA-R. Taken together, these data indicate that reduced Ehmt1 dosage during forebrain development leads to abnormal circuitry formation, which in turn results in profound information processing deficits. Such information processing deficits are likely paramount to our understanding of the cognitive and neurological dysfunctions shared across the neurodevelopmental disorders associated with EHMT1 haploinsufficiency.

scholarly journals Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders

2020 ◽  
Vol 14 ◽  
Author(s):  
Daisuke Ibi ◽  
Genki Nakasai ◽  
Nayu Koide ◽  
Masahito Sawahata ◽  
Takao Kohno ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Abnormal Behavior

scholarly journals Specific profile of ultrasonic communication in a mouse model of neurodevelopmental disorders

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marika Premoli ◽  
Sara Anna Bonini ◽  
Andrea Mastinu ◽  
Giuseppina Maccarinelli ◽  
Francesca Aria ◽  
...  
Keyword(s):  
Mouse Model ◽  
Social Communication ◽  
Neurodevelopmental Disorders ◽  
Environmental Enrichment ◽  
Maternal Separation ◽  
Wild Type ◽  
Social Investigation ◽  
Behavioural Phenotyping ◽  
Ultrasonic Communication ◽  
Specific Profile

Abstract Mice emit ultrasonic vocalizations (USVs) in different social conditions: pups maternal separation, juveniles play, adults mating and social investigation. The USVs measurement has become an important instrument for behavioural phenotyping in neurodevelopmental disorders (NDDs). Recently, we have demonstrated that the deletion of the NFκB1 gene, which encodes the p50 NF-κB subunit, causes NDDs phenotype in mice. In this study, we investigated the ultrasonic communication and the effects of an early social enrichment in mice lacking the NF-κB p50 subunit (p50 KO). In particular, USVs of wild-type (WT), p50 KO and KO exposed to early social enrichment (KO enriched) were recorded using an ultrasound sensitive microphone and analysed by Avisoft software. USVs analysis showed that p50 KO pups emit more and longer vocalizations compared to WT pups. On the contrary, in adulthood, p50 KO mice emit less USVs than WT mice. We also found significant qualitative differences in p50 KO mice USVs compared to WT mice; the changes specifically involved two USVs categories. Early social enrichment had no effect on USVs number, duration and type in p50 KO mice. Together, these data revealed social communication alterations in a mouse model of NDDs; these deficits were not recovered by early social enrichment, strengthening the fact that genetic background prevails on environmental enrichment.

scholarly journals Involvement of cAMP-Dependent Protein Kinase in the Nucleus Accumbens in Cocaine Versus Social Interaction Reward

2020 ◽  
Vol 22 (1) ◽  
pp. 345
Author(s):  
Inês M. Amaral ◽  
Cristina Lemos ◽  
Isabella Cera ◽  
Georg Dechant ◽  
Alex Hofer ◽  
...  
Keyword(s):  
Social Interaction ◽  
Nucleus Accumbens ◽  
Essential Role ◽  
Social Preference ◽  
Reward Learning ◽  
Social Reward ◽  
Dependent Protein Kinase ◽  
Natural Reward ◽  
Affect Expression ◽  
Dependent Protein

Evidence suggests that PKA activity in the nucleus accumbens (NAc) plays an essential role in reward-related learning. In this study, we investigated whether PKA is differentially involved in the expression of learning produced by either natural reinforcers or psychostimulants. For that purpose, we inhibited PKA through a bilateral infusion of Rp-cAMPS, a specific PKA inhibitor, directly into the NAc. The effects of PKA inhibition in the NAc on the expression of concurrent conditioned place preference (CPP) for cocaine (drug) and social interaction (natural reward) in rats were evaluated. We found that PKA inhibition increased the expression of cocaine preference. This effect was not due to altered stress levels or decreased social reward. PKA inhibition did not affect the expression of natural reward as intra-NAc Rp-cAMPS infusion did not affect expression of social preference. When rats were trained to express cocaine or social interaction CPP and tested for eventual persisting preference 7 and 14 days after CPP expression, cocaine preference was persistent, but social preference was abolished after the first test. These results suggest that PKA in the NAc is involved in drug reward learning that might lead to addiction and that only drug, but not natural, reward is persistent.

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