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个人简介
Research and Practice Interests
(1) Antidepressant Risks: We have shown that third-trimester-equivalent exposure to an SSRI causes learning deficits in rat offspring and reductions in serotonin. New clinical evidence indicates that prenatal SSRI exposure increases the risk of Autism Spectrum Disorder (ASD). In new studies, we are testing social, emotional, and cognitive functions. We are also collaborating with Dr. Steve Danzer. He developed a mouse in which the tumor suppressor gene, Pten, is deleted in the hippocampus. These KO mice show a phenotype consistent with ASD.
(2) Attention Deficit: ADHD affects 9.5% of school age children. Concordance among monozygotic twins is 80%, and 30% among dizygotic twins. Studies have identified the Latrophilin-3 (LPHN3) gene with ADHD. Recently, it was found that Flrt3 binds to the extracellular domain of Lphn3. We have an Lphn3 KO rat that shows hyperactivity, hyper-reactivity, and impaired sensorimotor gating. We are determining if Lphn3 KO rats show inattention and impulsivity, and whether medications reverse these effects.
(3) Depression: Despite success, up to 50% of patients do not benefit or benefit incompletely from these medications. No new antidepressant has been developed in 25 years. We created a KO mouse of phosphodiesterase-1B (Pde1b). PDEs hydrolyze cAMP and cGMP. PDE4 inhibitors were effective antidepressants but had adverse side-effects. Pde1b KO mice have an antidepressant phenotype. We are working with a company that has a Pde1 agonist. The drug has antidepressant activity in WT mice but not in KO mice.
(4) Environmental Agents: High manganese (Mn) exposure causes Parkinson-like, but effects during development are poorly understood. Mn is affected by iron. In those with iron insufficiency, Mn more readily crosses the blood brain barrier. We are developing a model of iron-insufficiency in combination with Mn and barren cages
(5) Insecticides: Pyrethroids are among the most widely used insecticides in the world. In recent years questions have arisen about the safety of some of the most widely used pyrethroids for children who are exposed when these are sprayed in schools, playgrounds, lawns, and in canned spray insecticides. We tested the effects of one of these, deltamethrin, given to rats shortly after birth for 3 weeks. As adults, the rats had learning impairments and differential responses to the NMDA receptor antagonist MK-801. They also showed differences in several markers of dopamine function in the brain. These studies are continuing to identify the mechanisms that underlies these long-term cognitive effects.
研究兴趣
论文共 444 篇作者统计合作学者相似作者
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CURRENT RESEARCH IN TOXICOLOGY (2024): 100151-100151
Neurotoxicology and Teratology (2024): 107356-107356
Chiho Sugimoto, Marla K. Perna,Samantha L. Regan,Erin A. Tepe, Rosalyn Liou,Adam L. Fritz,Michael T. Williams,Charles V. Vorhees,Matthew R. Skelton
BRAIN RESEARCH (2024)
Neurotoxicology and Teratology (2023): 107276-107276
NEUROTOXICOLOGY AND TERATOLOGY (2023): 1094698-1094698
Monica S. Carbajal,Asiah J. C. Bounmy, Olivia B. Harrison,Hunter G. Nolen,Samantha L. Regan,Michael T. Williams,Charles V. Vorhees,Helen J. K. Sable
Proceedings of the National Academy of Sciences of the United States of Americano. 24 (2023)
Neurotoxicology and Teratology (2023): 107271-107271
Chiho Sugimoto, Marla K Perna,Samantha L Regan,Erin A Tepe, Rosalyn Liou,Adam L Fritz,Michael T Williams,Charles V Vorhees,Matthew R Skelton
Brain research (2023): 148690-148690
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