Article
Neurosciences
Kaleb Dee Miles, Caleb Andrew Doll
Summary: Developmental changes in ionic balance play a crucial role in neural circuit formation. The shift of GABAergic neurotransmission from depolarizing to hyperpolarizing output is induced by changes in Cl- gradients and is delayed in Fragile X syndrome (FXS) models. The absence of FMRP protein, which regulates chloride transporter expression, can significantly impact FXS phenotypes. This perspective summarizes the expression of Cl- transporters and discusses the imbalances in inhibitory neurotransmission in FXS, highlighting potential therapeutic strategies.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Bernard J. Varian, Katherine T. Weber, Lily J. Kim, Tony E. Chavarria, Sebastian E. Carrasco, Sureshkumar Muthupalani, Theofilos Poutahidis, Marwa Zafarullah, Reem R. Al Olaby, Mariana Barboza, Kemal Solakyildirim, Carlito Lebrilla, Flora Tassone, Fuqing Wu, Eric J. Alm, Susan E. Erdman
Summary: Maternal microbial dysbiosis may be related to adverse postnatal health conditions in infants. This study found that mice fed a Westernized diet with low fiber and extra fat resulted in offspring exhibiting phenotypes similar to Fragile X Syndrome. The researchers hypothesized that gut dysbiosis and inflammation during pregnancy may affect the prenatal uterine environment, leading to abnormal phenotypes in offspring. Supplementation with the anti-inflammatory probiotic microbe Lactobacillus reuteri during pregnancy was able to inhibit the FXS-like phenotypes in offspring. These findings suggest a strong association between diet-induced dysbiosis in the prenatal uterine environment and the incidence of neurological phenotypes in offspring.
Review
Cell Biology
Toshihiro Nomura
Summary: The imbalance of excitatory-inhibitory (E-I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD, and deficits in inhibitory circuits in FXS tip the E-I balance towards excitation. Manipulating the activity of inhibitory interneurons can ameliorate symptoms in FXS, suggesting the potential for targeting interneurons to correct disrupted E-I balance in FXS.
Review
Immunology
Lisa C. Gibbs, Keke C. Fairfax
Summary: Maternal infection during pregnancy can affect the development and function of offspring's immune system, leading to abnormal responses to childhood infections and immunizations. However, research on maternal parasitic infections is lacking, and many infected pregnant women are unable to receive mass drug administration due to lack of resources and concerns about adverse fetal outcomes.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Neurosciences
Luis A. Milla, Lucia Corral, Jhanpool Rivera, Nolberto Zuniga, Gabriela Pino, Alexia Nunez-Parra, Christian A. Cea-Del Rio
Summary: Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by the mutation and silencing of the FMR1 gene, leading to loss of FMRP expression. FXS is characterized by abnormal regulation of neuronal development, resulting in cognitive and behavioral phenotypes. This review highlights the importance of therapeutically targeting critical developmental periods, such as early postnatal stages, and discusses the past and current clinical trials in FXS. The potential benefits, limitations, and disadvantages of pharmacological approaches are also discussed based on preclinical and clinical research.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Ming F. Lu, Qiang Fu, Tian Y. Qiu, Jian H. Yang, Qing H. Peng, Zhen Z. Hu
Summary: This study reveals a new mechanism by which pCaMKII-GABA(B)R signaling can promote psychostimulant-induced behavioral sensitization. It was found that GABA(B)R in the nucleus accumbens affects the development of cocaine-induced behavioral sensitization by mediating its perinucleus internalization and membrane expression. Moreover, the membrane levels of GABA(B)R were decreased while the membrane expression of pCaMKII was increased after repeated cocaine treatment.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Dejan B. Budimirovic, Kelli C. Dominick, Lidia Gabis, Maxwell Adams, Mathews Adera, Linda Huang, Pamela Ventola, Nicole R. Tartaglia, Elizabeth Berry-Kravis
Summary: This study aimed to evaluate the safety, tolerability, efficacy, and optimal daily dose of the GABA(A) receptor agonist OV101 in patients with FXS. Results showed that OV101 was well tolerated across different treatment regimens and demonstrated potential efficacy in improving symptoms of FXS.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Yeri J. Song, Bo Xing, Aaron J. Barbour, Chengwen Zhou, Frances E. Jensen
Summary: This study found alterations in GABA(A) receptor-mediated inhibitory synaptic transmission in Fragile X syndrome models, affecting the maturation of E-I circuitry and synaptic plasticity, leading to impaired critical period and auditory deficits in the auditory cortex.
Article
Medicine, General & Internal
Coral Garcia-Gonzalez, Elena Nunez, Huijing Zhang, Kypros H. Nicolaides, Marietta Charakida
Summary: Hypertensive disorders of pregnancy (HDP) may increase cardiovascular risk for the mother, but it is unclear whether there are cardiovascular changes in the postpartum period. This study recruited women with HDP and compared them to a control group to assess maternal and offspring cardiac function. The results showed that mothers with HDP had higher blood pressure, higher left-ventricular mass, and reduced left-ventricular diastolic function postpartum. However, there were no significant differences in cardiac function between groups for the offspring. These findings suggest the need for cardio-obstetric follow-up for mothers with HDP in the postpartum period.
Article
Pediatrics
Hui Xing Lau, Michelle Zhi Ling Kee, Qai Ven Yap, Elizabeth Huiwen Tham, Yiong Huak Chan, Anne Eng Neo Goh, Oon Hoe Teoh, Johan Gunnar Eriksson, Keith M. Godfrey, Peter D. Gluckman, Yap Seng Chong, Jerry Kok Yen Chan, Hugo Van Bever, Bee Wah Lee, Lynette Pei-chi Shek, Michael J. Meaney, Evelyn Xiu Ling Loo
Summary: The study found that maternal distress during the preconception and pregnancy periods is associated with an increased risk of offspring wheeze in the first 18 months of life. Emotional and practical support from family can reduce the risk of offspring wheeze.
FRONTIERS IN PEDIATRICS
(2022)
Article
Psychiatry
Heather Fielding-Gebhardt, Rebecca Swinburne Romine, Shelley Bredin-Oja, Nancy Brady, Steven F. Warren
Summary: Mothers of children with fragile X syndrome are more likely to experience anxiety and depression due to genetic risk and parenting stress. During the COVID-19 pandemic, their levels of anxiety and depression were elevated. The impacts of the pandemic and related stressors on their families directly affected their mental well-being.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Shifeng Xue, Thanh Thao Nguyen Ly, Raunak S. Vijayakar, Jingyi Chen, Joel Ng, Ajay S. Mathuru, Frederique Magdinier, Bruno Reversade
Summary: This study reveals that Smchd1 regulates Hox gene expression at an epigenetic level in mammals, and its loss causes precocious and ectopic Hox transcription. The loss of maternal Smchd1 also leads to Hox epimutations and affects the vertebral patterning in offspring. Furthermore, the regulation is mediated by the direct interacting partner Lrif1.
NATURE COMMUNICATIONS
(2022)
Article
Psychology, Biological
Yingchun Shang, Runwen Chen, Fangjuan Li, Hui Zhang, Haiyun Wang, Tao Zhang
Summary: Prenatal stress has negative effects on cognitive, behavioral, and physical health of offspring, especially in the early developmental stage. Studies suggest that the GABA system plays a key role in this process, and prenatal stress may disrupt GABA function, affecting memory and hippocampal synaptic plasticity.
PHYSIOLOGY & BEHAVIOR
(2021)
Review
Psychiatry
Khaleel A. Razak, Devin K. Binder, Iryna M. Ethell
Summary: This study explored the association between autism spectrum disorders and sensory processing disorders, as well as the neural correlates of Fragile X Syndrome. Findings indicated that individuals with Fragile X Syndrome often exhibit atypical sensory processing, including auditory hypersensitivity. By analyzing Fmr1 KO mice, the study revealed the neural mechanisms underlying auditory hypersensitivity and proposed new therapeutic approaches.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Neurosciences
Rachel E. Martin, Madison T. Green, Jessica A. Kinkade, Robert R. Schmidt, Tess E. Willemse, A. Katrin Schenk, Jiude Mao, Cheryl S. Rosenfeld
Summary: The research demonstrates that maternal exposure to oxycodone can result in neurobehavioral disorders and gene expression changes in offspring. These offspring showed persistent alterations in social communication, cognitive impairments, and other negative effects, possibly due to epigenetic changes in the brain.