S137. Long-Term Effects of Vortioxetine (Lu AA21004) on Adult Hippocampal Neurogenesis Prevents Reinstatement of Anxiety/Depression-Like Phenotype in Mice

Background: Alzheimer’s disease (AD), with cognitive impairment as the main clinical manifestation, is a progressive neurodegenerative disease. The assembly of amyloid-β (Aβ) as senile plaques is one of the most well-known histopathological alterations in AD. Several studies reported that cognitive training reduced Aβ deposition and delayed memory loss. However, the long-term benefits of spatial training and the underlying neurobiological mechanisms have not yet been elucidated. Objective: To explore the long-term effects of spatial training on AD-related pathogenic processes in APP/PS1 mice. Methods: We used Morris water maze (MWM), Open Field, Barnes Maze, western blotting, qPCR, and immunofluorescence. Results: One-month MWM training in APP/PS1 mice at 2.5 months of age could attenuate Aβ deposition and decrease the expression of β-secretase (BACE1) and amyloid-β protein precursor (AβPP) with long-term effects. Simultaneously, regular spatial training increased the expression of synapse-related proteins in the hippocampus. Moreover, MWM training increased adult hippocampal neurogenesis in AD model mice. Nonetheless, cognitive deficits in APP/PS1 transgenic mice at 7 months of age were not attenuated by MWM training at an early stage. Conclusion: Our study demonstrates that MWM training alleviates amyloid plaque burden and adult hippocampal neurogenesis deficits with long-term effects in AD model mice.

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Long-term effects of autoimmune CNS inflammation on adult hippocampal neurogenesis

Journal of Neuroscience Research ◽

10.1002/jnr.23982 ◽

2016 ◽

Vol 95 (7) ◽

pp. 1446-1458 ◽

Cited By ~ 14

Author(s):

Aggeliki Giannakopoulou ◽

George A. Lyras ◽

Nikolaos Grigoriadis

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Long Term Effects ◽

Cns Inflammation

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Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

Frontiers in Neuroscience ◽

10.3389/fnins.2014.00174 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 28

Author(s):

Christina M. Merkley ◽

Charles Jian ◽

Adam Mosa ◽

Yao-Fang Tan ◽

J. Martin Wojtowicz

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Homeostatic Regulation ◽

Long Term Effects ◽

Aging Rats ◽

Early Exercise

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Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

Scientific Reports ◽

10.1038/s41598-021-84600-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mariano Guardia Clausi ◽

Alexander M. Stessin ◽

Zirun Zhao ◽

Stella E. Tsirka ◽

Samuel Ryu

Keyword(s):

Brain Tissue ◽

Cranial Irradiation ◽

Subcortical White Matter ◽

Glioma Cell Line ◽

Hippocampal Neurogenesis ◽

Normal Brain ◽

Long Term Effects ◽

Normal Brain Tissue ◽

Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

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Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

Current Medicinal Chemistry ◽

10.2174/0929867328666210923143713 ◽

2021 ◽

Vol 28 ◽

Author(s):

Lucas Alexandre Santos Marzano ◽

Fabyolla Lúcia Macedo de Castro ◽

Caroline Amaral Machado ◽

João Luís Vieira Monteiro de Barros ◽

Thiago Macedo e Cordeiro ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Clinical Studies ◽

Molecular Mechanisms ◽

Hippocampal Neurogenesis ◽

Cognitive Outcomes ◽

Adult Hippocampal Neurogenesis ◽

The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

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Long-Term Overconsumption of Sugar Starting at Adolescence Produces Persistent Hyperactivity and Neurocognitive Deficits in Adulthood

Frontiers in Neuroscience ◽

10.3389/fnins.2021.670430 ◽

2021 ◽

Vol 15 ◽

Author(s):

Kate Beecher ◽

Ignatius Alvarez Cooper ◽

Joshua Wang ◽

Shaun B. Walters ◽

Fatemeh Chehrehasa ◽

...

Keyword(s):

Dietary Habits ◽

Hippocampal Neurogenesis ◽

Neurocognitive Deficits ◽

Long Term Effects ◽

Sugar Consumption ◽

Food And Beverages ◽

Increased Risk ◽

Newborn Neurons ◽

Dependent Learning

Sugar has become embedded in modern food and beverages. This has led to overconsumption of sugar in children, adolescents, and adults, with more than 60 countries consuming more than four times (>100 g/person/day) the WHO recommendations (25 g/person/day). Recent evidence suggests that obesity and impulsivity from poor dietary habits leads to further overconsumption of processed food and beverages. The long-term effects on cognitive processes and hyperactivity from sugar overconsumption, beginning at adolescence are not known. Using a well-validated mouse model of sugar consumption, we found that long-term sugar consumption, at a level that significantly augments weight gain, elicits an abnormal hyperlocomotor response to novelty and alters both episodic and spatial memory. Our results are similar to those reported in attention deficit and hyperactivity disorders. The deficits in hippocampal-dependent learning and memory were accompanied by altered hippocampal neurogenesis, with an overall decrease in the proliferation and differentiation of newborn neurons within the dentate gyrus. This suggests that long-term overconsumption of sugar, as that which occurs in the Western Diet might contribute to an increased risk of developing persistent hyperactivity and neurocognitive deficits in adulthood.

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Estrogenic Regulation of Hippocampal Neurogenesis Throughout the Lifespan

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0016 ◽

2020 ◽

pp. 253-281

Author(s):

Shunya Yagi ◽

Rand S. Eid ◽

Wansu Qiu ◽

Paula Duarte-Guterman ◽

Liisa A. M. Galea

Keyword(s):

Steroid Hormones ◽

Cognitive Training ◽

Adult Female ◽

Ovarian Hormones ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Maternal Experience ◽

Number Of Factors ◽

Estrogenic Regulation

Neurogenesis in the hippocampus exists across a number of species, including humans. Steroid hormones, such as estrogens, modulate neurogenesis dependent on age, reproductive experience and sex. Findings are discussed in the chapter with reference to how neurogenesis in the hippocampus is related to learning and memory. Natural fluctuations in ovarian hormones or removal of ovaries modulate neurogenesis in the short term but not in the long term. Maternal experience has long-lasting effects on neurogenesis in the hippocampus. Acute estrogens increase proliferation in adult female rodents, but influence survival of new neurons dependent on a number of factors including sex, cognitive training, type of estrogen, and whether or not cells were produced under estrogens. This chapter outlines findings indicating that estrogens can be strong modulators of adult hippocampal neurogenesis, which may have implications for disorders involving hippocampal dysfunction that target women.

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Long-Term Changes of Symptoms of Anxiety, Depression, and Fatigue in Cancer Patients 6 Months After the End of Yoga Therapy

Integrative Cancer Therapies ◽

10.1177/1534735418822096 ◽

2019 ◽

Vol 18 ◽

pp. 153473541882209 ◽

Cited By ~ 3

Author(s):

Anna Lundt ◽

Elisabeth Jentschke

Keyword(s):

Cancer Patients ◽

Controlled Study ◽

Life Questionnaire ◽

Long Term Effects ◽

European Organization ◽

Yoga Therapy ◽

Randomized Controlled ◽

Long Term Changes ◽

Anxiety Depression

Background: Symptoms of anxiety, depression, and cancer-related fatigue are commonly associated with cancer. Cancer patients increasingly use complementary and alternative treatments, such as yoga, to cope with psychological and physical impairments. In the present article, long-term changes of anxiety, depression, and fatigue in cancer are examined 6 months after a yoga intervention. Method: We used an observational design based on a randomized controlled study in cancer patients with mixed diagnoses to evaluate long-term changes of symptoms of anxiety, depression, and fatigue 6 months after the end of yoga therapy. We measured anxiety symptoms with the Generalized Anxiety Disorder scale (GAD-7), depressive symptoms with the Patient Health Questionnaire–2 (PHQ-2), and fatigue with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Fatigue Scale (EORTC QLQ-FA13). Yoga therapy was provided in yoga classes of 60 minutes each once a week for 8 weeks in total. The exercises provided contained both body and breathing activities as well as meditation. Results: A total of 58 patients participated in the study. Six months after the end of yoga therapy, symptoms of anxiety, depression, and fatigue were significantly reduced compared with baseline. However, symptoms of anxiety and fatigue slightly increased during the follow-up period, whereas symptoms of depression remained stable. Conclusion: Our results are promising and support the integration of yoga interventions in supportive cancer treatment concepts but should be confirmed by randomized controlled trials. Long-term effects of yoga therapy on cancer patients should be the subject of further research.

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