Li 2014: CRH Autism

Li, H., Zhong, X., Chau, K. F., Williams, E. C., Chang, Q., & Xu, B. (2014). MeCP2 binds to CRH and regulates anxiety-related behaviors. Nature Neuroscience, 17(12), 1637–1645. doi: 10.1038/nn.3866 

This study investigated the role of the protein MeCP2, which is mutated in Rett Syndrome, a neurodevelopmental disorder that is often comorbid with autism spectrum disorder (ASD), in regulating anxiety-related behaviors.

The researchers found that MeCP2 binds to corticotrophin-releasing hormone (CRH) and regulates its expression in the paraventricular nucleus of the hypothalamus (PVN), a region of the brain known to be involved in stress and anxiety. They also found that mice with a mutation in MeCP2 had hyperactivity of CRH-PVN neurons and exhibited increased anxiety-like behaviors.

The study suggests that the hyperactivity of CRH-PVN neurons may contribute to the anxiety and social deficits observed in Rett Syndrome and possibly in ASD. The findings also highlight the importance of MeCP2 in regulating the expression of genes involved in the development and function of the brain.

Lee et al 2014 . GABAergic inhibition and Sleep-Wake cycle

 

1. Lee, E., Lee, J., Kim, E., Park, J., & Kim, Y. (2014). GABAergic inhibition of histaminergic neurons regulates active waking but not the sleep-wake switch or propofol-induced loss of consciousness. Nature Communications, 5, 4249. doi: 10.1038/ncomms5249

The study by Lee et al. (2014) investigated the role of GABAergic inhibition on histaminergic neurons in regulating sleep and wakefulness. The researchers focused on two specific aspects of sleep-wake regulation: active waking and the sleep-wake switch.

Active waking is a state of wakefulness in which an individual is alert and engaged in various activities, whereas the sleep-wake switch refers to the transition between sleep and wakefulness. The researchers used mice as a model organism and performed experiments to investigate the effects of GABAergic inhibition on these two aspects of sleep-wake regulation.

The researchers found that GABAergic inhibition of histaminergic neurons played a significant role in regulating active waking, but had no effect on the sleep-wake switch or propofol-induced loss of consciousness. This suggests that the histaminergic system may be specifically involved in regulating the state of active waking, which is characterized by increased attention and motor activity.

Overall, this study sheds light on the complex neural mechanisms involved in sleep-wake regulation and highlights the importance of GABAergic inhibition in controlling specific aspects of wakefulness. The findings have potential implications for the development of new treatments for sleep disorders and disorders of consciousness.

Zhong et al. (2019) : Autism and CRH-PVN

Zhong, S., Zhang, S., Fan, X., Wu, Q., Yan, L., Dong, J., & Li, L. (2019). Paraventricular nucleus corticotrophin-releasing hormone neurons mediate social behavioral deficits in a mouse model of autism. Translational Psychiatry, 9(1), 26. doi: 10.1038/s41398-019-0385-1 can you expand on findings in this paper

The study by Zhong et al. (2019) aimed to investigate the role of CRH-PVN neurons in social behavior deficits in a mouse model of ASD. The researchers used a mouse model that had a mutation in the SHANK3 gene, which is a gene that has been strongly associated with ASD in humans.

The authors found that mice with the SHANK3 mutation had alterations in the activity of CRH-PVN neurons compared to wild-type mice. Specifically, they found that the SHANK3 mutant mice had decreased activity of CRH-PVN neurons during social interaction compared to wild-type mice. They also found that optogenetic stimulation of CRH-PVN neurons in the SHANK3 mutant mice rescued social interaction deficits, suggesting that the deficits were due to the altered activity of these neurons.

The authors further showed that the social behavior deficits in the SHANK3 mutant mice were mediated by the CRH-PVN system. They found that infusion of a CRH antagonist into the PVN of the SHANK3 mutant mice improved social interaction deficits, while infusion of CRH into the PVN of wild-type mice impaired social interaction.

Overall, these findings suggest that alterations in the activity of CRH-PVN neurons may contribute to social behavior deficits in ASD. The study highlights the potential of targeting the CRH-PVN system as a therapeutic approach for ASD.

Sokolowski et al. (2017)

1. Sokolowski, K., Corbin, J. G., & Scherer, S. W. (2017). Autism spectrum disorder: old targets and new genes. Molecular Psychiatry, 22(4), 519-535. doi: 10.1038/mp.2016.198

 

The study by Sokolowski et al. (2017) aimed to investigate genetic and biological factors underlying ASD. The authors performed a comprehensive review of genetic studies on ASD, as well as studies examining various biological markers associated with ASD.

One of the markers they examined was corticotropin-releasing hormone (CRH), which is released by CRH-PVN neurons in the hypothalamus and is involved in the body's stress response system. The authors found that several studies have reported elevated levels of CRH in the cerebrospinal fluid of individuals with ASD compared to typically developing individuals.

The authors also discussed the potential role of the CRH-PVN system in the development of ASD. They noted that CRH-PVN neurons have been shown to play a critical role in the regulation of the HPA axis, which is involved in the body's response to stress. Dysregulation of the HPA axis has been reported in individuals with ASD, suggesting a potential role for the CRH-PVN system in the development of ASD.

Overall, the findings of the study suggest that dysregulation of the CRH-PVN system may be one of the biological factors underlying ASD. However, more research is needed to fully understand the role of this system in the development and pathophysiology of ASD.