Article
Neurosciences
Sheikh Mizanur Rahaman, Srikanta Chowdhury, Yasutaka Mukai, Daisuke Ono, Hiroshi Yamaguchi, Akihiro Yamanaka
Summary: GABAergic neurons in the ventral tegmental area (VTA) are responsive to different neurotransmitters and play a role in regulating sleep/wakefulness. These neurons have projections in brain areas related to sleep/wakefulness and are activated by cholinergic agonists, but inhibited by serotonin, dopamine, and histamine. VTA(Gad67+) neurons inhibit neurons in the dorsal raphe nucleus (DRN), but not in the central amygdala (CeA) and locus coeruleus (LC). They also monosynaptically inhibit serotonergic neurons in the DRN (DRN5-HT).
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Clinical Neurology
Ping Cai, Fu-Dan Wang, Jing Yao, Wen-Feng Wang, Yu-Duan Hu, Ren-Fu Liu, Zhang-Shu Li, Zhong-Hua Zhu, Yu-Tong Cai, Zhi-Hui Lin, Wei-Tao Tang, Cong-Wen Zhuang, Wen-Hao Xiao, Yu-Hang Zeng, Sheng-Nan Huang, Zhifei Fu, Wen-Xiang Wang, Li Chen
Summary: This study demonstrates the importance of GABAergic neurons in the dorsal raphe nucleus (DRN) in the induction and maintenance of wakefulness, promoting wakefulness through the GABAergic DRN-VTA pathway.
Review
Biology
Zachary A. Grieb, Joseph S. Lonstein
Summary: The interaction between oxytocin and central dopamine and serotonin systems is crucial for behavioral adaptations during the postpartum period. Oxytocin-dopamine interaction regulates maternal motivation and active caregiving behaviors, while oxytocin-serotonin interaction influences other aspects such as nursing, aggression, anxiety-like behavior, and stress coping strategy.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Tatyana Strekalova, Evgeniy Svirin, Jonas Waider, Anna Gorlova, Raymond Cespuglio, Allan Kalueff, Igor Pomytkin, Angelika G. Schmitt-Boehrer, Klaus-Peter Lesch, Daniel C. Anthony
Summary: Gene-environment interaction determines vulnerability to stress-related neuropsychiatric disorders, with Tph2 gene variants linked to increased impulsivity and aggression. Tph2+/- mice exhibit increased aggression, reduced sociability, and altered brain metabolism of serotonin, dopamine, and norepinephrine after predator stress exposure, showing resilience to stress. This study highlights how GxE interaction studies can reveal genetically determined predispositions and uncover latent behaviors.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Review
Behavioral Sciences
Emmanuelle Courtiol, Edenia C. Menezes, Catia M. Teixeira
Summary: Serotonin plays a critical role in development and behavior, with its involvement in reward being a topic of debate. Classical studies using electrical stimulation and pharmacological approaches have produced contradictory results on the role of serotonin in reward. More recent optogenetic studies suggest that activation of the serotonergic cells in the Raphe to VTA pathway can mediate reinforcement learning through the excitation of dopaminergic neurons. Understanding the interaction between the serotonergic and dopaminergic systems is crucial for insights into neuropsychiatric disorders.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Review
Neurosciences
Martin Metzger, Rudieri Souza, Leandro B. Lima, Debora Bueno, Luciano Goncalves, Chemutai Sego, Jose Donato, Sara J. Shammah-Lagnado
Summary: The habenula is an ancient epithalamic structure divided into medial and lateral complexes that play important roles in encoding aversive stimuli and loss of predicted rewards. Aberrant activity in the lateral habenula has been linked to major depressive disorder. Both medial and lateral habenula are involved in the reward circuitry and connected to monoaminergic nuclei in the brainstem, potentially mediating some functions through this complex network.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Matthew E. Glover, Keaton A. Unroe, Mohamad M. Moughnyeh, Chelsea McCoy, Ilan A. Kerman, Sarah M. Clinton
Summary: Serotonin plays a crucial role in regulating various functions and neurodevelopmental processes, and its genetic and environmental factors can have an impact on brain structure and behavior, potentially contributing to neuropsychiatric disorders.
NEUROSCIENCE LETTERS
(2022)
Article
Behavioral Sciences
Zhang-Lin Liu, Xin-Qiang Wang, Ming-fan Liu, Bao-juan Ye
Summary: The TPH2 gene polymorphisms are associated with depression, with significant results in Chinese subjects. Further biological experiments are needed to understand the effects of different SNPs on depression.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Rosanna Caputo, Vincent-Joseph Poirel, Etienne Challet, Johanna H. Meijer, Sylvie Raison
Summary: This study investigates the functioning of the serotonin system in diurnal rodents. The results show that the synthesis of serotonin in these animals is rhythmic and correlates with their behavioral phenotype.
Article
Neurosciences
Sheila A. Engi, Erin J. Beebe, Victoria M. Ayvazian, Fabio C. Cruz, Joseph F. Cheer, Jennifer M. Wenzel, Natalie E. Zlebnik
Summary: Mesolimbic dopamine plays a crucial role in motivated behavior, with CB1 receptor signaling in the VTA being implicated in the phasic activation of dopamine. Cocaine-induced increases in motivation appear to require 2-AG signaling at CB1 receptors in the VTA, suggesting potential cannabinoid-based pharmacotherapeutic targets for substance abuse treatment.
Article
Biochemistry & Molecular Biology
Grazyna Jerzemowska, Karolina Plucinska, Aleksandra Piwka, Magdalena Podlacha, Jolanta Orzel-Gryglewska
Summary: In this study, the researchers investigated the role of opioid receptors (OR) in the pedunculopontine tegmental nucleus (PPN) in regulating motivated behaviors. They found that activation and blocking of OR in the PPN affected behavioral and neuronal activity, modulating the reward system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Wojciech B. Solecki, Michal Kielbinski, Michal Wilczkowski, Katarzyna Zajda, Karolina Karwowska, Bernacka Joanna, Zenon Rajfur, Ryszard Przewlocki
Summary: This study reveals the impact of locus coeruleus cells on the ventral tegmental area dopamine reward system and their crucial role in cocaine-seeking behavior. Non-contingent inhibition of noradrenergic terminals in the locus coeruleus reduces cocaine seeking, while contingent inhibition increases it.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biology
Kevin Beier
Summary: This study used a modified viral-genetic strategy to investigate both local and long-range inputs to dopamine cells in the ventral tegmental area (VTA) in mice. The findings revealed that nearly half of the inputs to VTA cells are located locally, which were previously overlooked. The main source of inhibition to VTA cells is from the substantia nigra pars reticulata, with substantial contributions from the VTA and substantia nigra pars compacta. Dopamine neurons also have connections with other dopamine neurons within the VTA and the nearby retrorubal field. Additionally, the study showed that VTA neurons receive inputs from serotonergic neurons distributed throughout the midbrain and hindbrain, with the majority coming from the dorsal raphe.
Article
Psychology, Multidisciplinary
Guanmao Chen, Pan Chen, Zibin Yang, Wenhao Ma, Hong Yan, Ting Su, Yuan Zhang, Zhangzhang Qi, Wenjie Fang, Lijun Jiang, Zhuoming Chen, Qian Tao, Ying Wang
Summary: Bright light therapy (BLT) improves subthreshold depressive symptoms and increases connectivity between midbrain monoamine-producing nuclei and the frontal cortex. Baseline functional connectivity between the dorsal raphe nucleus (DRN) and medial prefrontal cortex (mPFC) can predict changes in depressive symptoms after BLT treatment.
AMERICAN PSYCHOLOGIST
(2023)
Article
Neurosciences
Anna Gugula, Aleksandra Trenk, Aleksandra Celary, Katarzyna Cizio, Grzegorz Tylko, Anna Blasiak, Grzegorz Hess
Summary: Early-life stress has long-term consequences, including an increased risk for drug abuse and psychiatric disorders later in life, higher in women than in men. This study reveals the changes in stress sensitivity of specific neuronal populations in the ventral tegmental area and lateral hypothalamus caused by early-life stress.
Article
Biochemistry & Molecular Biology
Amanda L. Sharpe, Marta Trzeciak, Nicole L. Eliason, Harris E. Blankenship, Bre' Ana M. Byrd, Phillip D. Douglas, Willard M. Freeman, Michael J. Beckstead
Summary: The study reveals that the expression of GLAST and CRF2 in astrocytes in the SN/VTA is significantly affected by psychostimulant drugs, which may influence neurotransmission and related behaviors.
Review
Pharmacology & Pharmacy
Christopher A. Legare, Wesley M. Raup-Konsavage, Kent E. Vrana
Summary: This review summarizes the therapeutic uses of cannabis and CBD oil. The data support the role of cannabis/cannabinoids in pain relief, seizure disorders, appetite stimulation, muscle spasticity, and treatment of nausea/vomiting, but the data for central nervous system disorders and cancer treatment are less compelling.
Article
Endocrinology & Metabolism
Samim Ali Mondal, Roshini Sathiaseelan, Shivani N. Mann, Maria Kamal, Wenyi Luo, Tatiana D. Saccon, Jose V. V. Isola, Frederick F. Peelor III, Tiangang Li, Willard M. Freeman, Benjamin F. Miller, Michael B. Stout
Summary: The naturally occurring diastereomer of 17β-estradiol, 17α-estradiol, can reduce liver fibrosis by suppressing hepatic stellate cell activation and enhancing collagen degradation mechanisms.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Correction
Obstetrics & Gynecology
Emily R. R. Smith, William M. M. Curtin, Kevin P. P. Yeagle, Nurgul Carkaci-Salli, Serdar H. H. Ural
REPRODUCTIVE SCIENCES
(2023)
Article
Neurosciences
Sarah R. Ocanas, Victor A. Ansere, Collyn M. Kellogg, Jose V. V. Isola, Ana J. Chucair-Elliott, Willard M. Freeman
Summary: Biological sex influences neurodegenerative diseases through genetic and hormonal mechanisms. Microglial reactivity and the pro-inflammatory environment of the aging brain are influenced by sex, age, and disease state. Further research is needed to understand the regulation of microglial sex effects and develop sex-informed prevention and treatment strategies for brain diseases.
BRAIN RESEARCH BULLETIN
(2023)
Article
Oncology
Sabira Mohammed, Nidheesh Thadathil, Phoebe Ohene-Marfo, Albert L. Tran, Michael Van Der Veldt, Constantin Georgescu, Sangphil Oh, Evan H. Nicklas, Dawei Wang, Nair Hariprasad Haritha, Wenyi Luo, Ralf Janknecht, Benjamin F. Miller, Jonathan D. Wren, Willard M. Freeman, Sathyaseelan S. Deepa
Summary: Blocking necroptosis reduces inflammation and hepatocellular carcinoma (HCC) in a mouse model of diet-induced HCC, particularly in male mice, suggesting necroptosis as a potential therapeutic target for NAFLD-mediated HCC.
MOLECULAR CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sarah R. Ocanas, Jose V. V. Isola, Tatiana D. Saccon, Kevin D. Pham, Ana J. Chucair-Elliott, Augusto Schneider, Willard M. Freeman, Michael B. Stout
Summary: Assessing cell-type-specific epigenomic and transcriptomic changes are key to understanding ovarian aging. The optimization of TRAP and INTACT methods were performed using a transgenic NuTRAP mouse model to study the ovarian transcriptome and epigenome in specific cell types.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Geriatrics & Gerontology
Michael B. B. Stout, Kelli L. L. Vaughan, Jose V. V. Isola, Shivani N. N. Mann, Bayli Wellman, Jessica M. M. Hoffman, Hunter L. L. Porter, Willard M. M. Freeman, Julie A. A. Mattison
Summary: Recent studies have shown that 17 alpha-estradiol can extend the healthspan and lifespan of male mice through multiple mechanisms, making it a potential candidate for translation into humans. However, there is currently no established dosing paradigm for the treatment of aging and chronic disease in humans. This study aimed to assess the tolerability of 17 alpha-estradiol treatment and evaluate metabolic and endocrine responses in male rhesus macaque monkeys during a short treatment period. The results showed that the dosing regimens were well-tolerated and had mild benefits on metabolic parameters, but significant feminization effects were observed.
Article
Immunology
Sarah R. Ocanas, Kevin D. Pham, Jillian E. J. Cox, Alex W. Keck, Sunghwan Ko, Felix A. Ampadu, Hunter L. Porter, Victor A. Ansere, Adam Kulpa, Collyn M. Kellogg, Adeline H. Machalinski, Manu A. Thomas, Zsabre Wright, Ana J. Chucair-Elliott, Willard M. Freeman
Summary: This study compared the transcriptome and translatome of hippocampal microglia between young and old mice and found sex differences in microglial gene expression. In old age, these differences were primarily female-biased and enriched in markers of senescence and disease. These findings may explain the differences in susceptibility and disease progression in Alzheimer's disease between males and females. Further studies are needed to explore the role of sex differences in microglial heterogeneity and the involvement of sex-specific regulators in response to Alzheimer's pathology.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Geriatrics & Gerontology
Victor A. Ansere, Matthew P. Bubak, Benjamin F. Miller, Willard M. Freeman
Summary: Experimental approaches like Heterochronic Plasma Transfer (HPT) are important tools for studying aging, but they have limitations and design challenges. This review provides insights into the considerations and caveats of HPT as a research tool, including plasma preparation, administration route, dosing regimen, and appropriate controls, to assist investigators in achieving their experimental goals.
REJUVENATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Nurgul Carkaci-Salli, Maria C. Bewley, Izel Tekin, John M. Flanagan, Kent E. Vrana
Summary: Human tryptophan hydroxylase 2 (hTPH2) is the rate-limiting enzyme for serotonin biosynthesis in the brain. A missense polymorphism rs2887147 (A328 V/E) in hTPH2 has been found to decrease enzyme activity and stability, while the variant A328E is inactive. In the absence of the N-terminal regulatory domain, the A328V substitution has no effect on enzyme activity and stability. This polymorphism-induced reduction in serotonin synthesis may contribute to behavioral perturbations, emotional stress, and eating disorders.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2023)
Article
Oncology
Michael Pennock, Balazs Halmos, William Bodner, Haiying Cheng, Rasim Gucalp, Nitin Ohri
Summary: For most locally advanced non-small cell lung cancer (LA-NSCLC) patients who complete definitive chemoradiotherapy (CRT) and do not experience disease progression, one year of adjuvant durvalumab is recommended. This study explores the causes and consequences of early durvalumab discontinuation and suggests that the extent of cardiac irradiation may be a risk factor for immunotherapy discontinuation, disease recurrence, and death.
CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY
(2023)
Article
Geriatrics & Gerontology
Collyn M. Kellogg, Kevin Pham, Adeline H. Machalinski, Hunter L. Porter, Harris E. Blankenship, Kyla B. Tooley, Michael B. Stout, Heather C. Rice, Amanda L. Sharpe, Michael J. Beckstead, Ana J. Chucair-Elliott, Sarah R. Ocanas, Willard M. Freeman
Summary: This study reveals that microglia are the primary source of MHC-I in mice and humans, with its expression increasing with aging and in Alzheimer's disease. The expression of Lilrs and Pilrs, MHC-I binding receptor families, also increases with aging and AD. These findings suggest the possibility of cell-autonomous MHC-I signaling in regulating microglial reactivation and neurodegeneration.
Article
Geriatrics & Gerontology
Ramasamy Selvarani, Hoang Van Michelle Nguyen, Nidheesh Thadathil, Roman F. Wolf, Willard M. Freeman, Christopher D. Wiley, Sathyaseelan S. Deepa, Arlan Richardson
Summary: This study utilized knockin mouse models to investigate the impact of necroptosis-induced chronic inflammation on aging and age-related diseases. The findings revealed a significant association between increased necroptosis, inflammation, and various age-related pathological changes.
Meeting Abstract
Ophthalmology
Ana J. Chucair-Elliott, Sarah Ocanas, Kevin Pham, Michael Van der Veldt, Ashley Cheyney, David Stanford, Michael H. Elliott, Willard Freeman
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)