The Association Between Medication, Dopamine Function, and Long-Term Symptom Severity in the Matured and Developing Brain in ADHD

Abstract Background Little is known about the extent of drug entry into developing brain, when administered to pregnant and lactating women. Lithium is commonly prescribed for bipolar disorder. Here we studied transfer of lithium given to dams, into blood, brain and cerebrospinal fluid (CSF) in embryonic and postnatal animals as well as adults. Methods Lithium chloride in a clinically relevant dose (3.2 mg/kg body weight) was injected intraperitoneally into pregnant (E15–18) and lactating dams (birth-P16/17) or directly into postnatal pups (P0–P16/17). Acute treatment involved a single injection; long-term treatment involved twice daily injections for the duration of the experiment. Following terminal anaesthesia blood plasma, CSF and brains were collected. Lithium levels and brain distribution were measured using Laser Ablation Inductively Coupled Plasma-Mass Spectrometry and total lithium levels were confirmed by Inductively Coupled Plasma-Mass Spectrometry. Results Lithium was detected in blood, CSF and brain of all fetal and postnatal pups following lithium treatment of dams. Its concentration in pups’ blood was consistently below that in maternal blood (30–35%) indicating significant protection by the placenta and breast tissue. However, much of the lithium that reached the fetus entered its brain. Levels of lithium in plasma fluctuated in different treatment groups but its concentration in CSF was stable at all ages, in agreement with known stable levels of endogenous ions in CSF. There was no significant increase of lithium transfer into CSF following application of Na+/K+ ATPase inhibitor (digoxin) in vivo, indicating that lithium transfer across choroid plexus epithelium is not likely to be via the Na+/K+ ATPase mechanism, at least early in development. Comparison with passive permeability markers suggested that in acute experiments lithium permeability was less than expected for diffusion but similar in long-term experiments at P2. Conclusions Information obtained on the distribution of lithium in developing brain provides a basis for studying possible deleterious effects on brain development and behaviour in offspring of mothers undergoing lithium therapy.

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Functions of Gtf2i and Gtf2ird1 in the developing brain: transcription, DNA-binding, and long term behavioral consequences

10.1101/854851 ◽

2019 ◽

Author(s):

Nathan D. Kopp ◽

Kayla R. Nygaard ◽

Katherine B. McCullough ◽

Susan E. Maloney ◽

Harrison W. Gabel ◽

...

Keyword(s):

Dna Binding ◽

Binding Sites ◽

Conditioned Fear ◽

Developing Brain ◽

Ctcf Binding ◽

Microdeletion Syndrome ◽

Behavioral Phenotypes ◽

Marble Burying ◽

And Behavior

AbstractGtf2ird1 and Gtf2i may mediate aspects of the cognitive and behavioral phenotypes of Williams Syndrome (WS) – a microdeletion syndrome encompassing these transcription factors (TFs). Knockout mouse models of each TF show behavioral phenotypes. Here we identify their genomic binding sites in the developing brain, and test for additive effects of their mutation on transcription and behavior. Both TFs target constrained chromatin modifier and synaptic protein genes, including a significant number of ASD genes. They bind promoters, strongly overlap CTCF binding and TAD boundaries, and moderately overlap each other, suggesting epistatic effects. We used single and double mutants to test whether mutating both TFs will modify transcriptional and behavioral phenotypes of single Gtf2ird1 mutants. Despite little difference in DNA-binding and transcriptome-wide expression, Gtf2ird1 mutation caused balance, marble burying, and conditioned fear phenotypes. However, mutating Gtf2i in addition to Gtf2ird1 did not further modify transcriptomic or most behavioral phenotypes, suggesting Gtf2ird1 mutation alone is sufficient.

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School Shootings and Trauma-Sensitive School Environment

10.4018/978-1-7998-5200-1.ch009 ◽

2022 ◽

pp. 164-189

Author(s):

Ezgi Ildirim

Keyword(s):

School Environment ◽

Traumatic Events ◽

Brain Structures ◽

Well Being ◽

School Shootings ◽

Developing Brain ◽

School Shooting ◽

Traumatic Symptoms

School shootings are traumatic events that have detrimental impacts on children. Studies revealed that after the school shooting children can suffer from traumatic symptoms which cause difficulties in learning and relationships. Traumas negatively affect developing brain structures of the children which can lead to long-term problems. For that reason, the trauma sensitive schools (TSS) model, which aimed to provide safe and secure environments for children, can be helpful to support the children and to improve their well-being after the school shooting.

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W1121 Long-Term Benefits of Dexlansoprazole MR on Quality of Life and Symptom Severity Among Gastroesophageal Reflux Disease (GERD) Patients

Gastroenterology ◽

10.1016/s0016-5085(10)63016-8 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-656

Author(s):

Reema Mody ◽

Stacie Hudgens ◽

Cong Han ◽

Maria Claudia Perez

Keyword(s):

Quality Of Life ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Symptom Severity

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Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3βSignaling Pathway

BioMed Research International ◽

10.1155/2016/7919640 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Guorong Tao ◽

Qingsheng Xue ◽

Yan Luo ◽

Guohui Li ◽

Yimeng Xia ◽

...

Keyword(s):

Signaling Pathway ◽

Learning And Memory ◽

Pediatric Anesthesia ◽

Developmental Neurotoxicity ◽

Developing Brain ◽

Spatial Learning And Memory ◽

Postnatal Exposure ◽

Multiple Exposures

Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3βsignaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3βand learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3βand learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β(ser9) expressions, which led to GSK3βoveractivation. Lithium prevented GSK3βoveractivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3βsignaling pathway partly participates in this process. GSK3βinhibition might be an effective way to protect against developmental neurotoxicity.

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