scholarly journals Lithium treatment and human hippocampal neurogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alish B. Palmos ◽  
Rodrigo R. R. Duarte ◽  
Demelza M. Smeeth ◽  
Erin C. Hedges ◽  
Douglas F. Nixon ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Dentate Gyrus ◽  
Lithium Treatment ◽  
Molecular Layer ◽  
Empirical Support ◽  
Hippocampal Volume ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
High Dose ◽  
Cell Parameters

AbstractLithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.75 mM) and high (2.25 mM) doses of lithium on human hippocampal progenitor cells and used immunocytochemistry to investigate the effects of lithium on cell parameters implicated in neurogenesis. Corresponding RNA-sequencing and gene-set enrichment analyses were used to evaluate whether genes affected by lithium in our model overlap with those regulating the volume of specific layers of the dentate gyrus. We observed that high-dose lithium treatment in human hippocampal progenitors increased the generation of neuroblasts (P ≤ 0.01), neurons (P ≤ 0.01), and glia (P ≤ 0.001), alongside the expression of genes, which regulate the volume of the molecular layer of the dentate gyrus. This study provides empirical support that adult hippocampal neurogenesis and gliogenesis are mechanisms that could contribute to the effects of lithium on human hippocampal volume.

scholarly journals Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

2016 ◽  
Vol 113 (18) ◽  
pp. E2536-E2545 ◽  
Author(s):  
Jonathan Moss ◽  
Elias Gebara ◽  
Eric A. Bushong ◽  
Irene Sánchez-Pascual ◽  
Ruadhan O’Laoi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dentate Gyrus ◽  
Radial Glia ◽  
Molecular Layer ◽  
Cell Activity ◽  
Local Environment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Granule Cell Layer ◽  
Neurogenic Niche

Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP–positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.

scholarly journals Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain

2020 ◽  
Vol 117 (41) ◽  
pp. 25818-25829
Author(s):  
Xinxing Wang ◽  
Hanxiao Liu ◽  
Johannes Morstein ◽  
Alexander J. E. Novak ◽  
Dirk Trauner ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Energy Homeostasis ◽  
Inhibitory Neuron ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Neuron Activity ◽  
Adult Mice ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms

Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study

2007 ◽  
Vol 195 (3) ◽  
pp. 357-367 ◽  
Author(s):  
Kaan Yucel ◽  
Margaret C. McKinnon ◽  
Valerie H. Taylor ◽  
Kathryn Macdonald ◽  
Martin Alda ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Lithium Treatment ◽  
Hippocampal Volume ◽  
Longitudinal Mri ◽  
Mri Study

scholarly journals Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalie N. Nawarawong ◽  
K. Ryan Thompson ◽  
Steven P. Guerin ◽  
Chinchusha Anasooya Shaji ◽  
Hui Peng ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Immature Neurons

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

scholarly journals Thyroid Functions and Bipolar Affective Disorder

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Subho Chakrabarti
Keyword(s):  
Bipolar Disorder ◽  
Affective Disorder ◽  
Clinical Course ◽  
Lithium Treatment ◽  
Bipolar Affective Disorder ◽  
High Dose ◽  
Careful Monitoring ◽  
Genetic Studies ◽  
Treatment Refractory ◽  
Hpt Axis

Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT) axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition.

scholarly journals Kruppel-Like Factor 9 Is Necessary for Late-Phase Neuronal Maturation in the Developing Dentate Gyrus and during Adult Hippocampal Neurogenesis

2009 ◽  
Vol 29 (31) ◽  
pp. 9875-9887 ◽  
Author(s):  
K. N. Scobie ◽  
B. J. Hall ◽  
S. A. Wilke ◽  
K. C. Klemenhagen ◽  
Y. Fujii-Kuriyama ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Late Phase ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Neuronal Maturation

Chronic stress targets adult hippocampal neurogenesis preferentially in the suprapyramidal blade of rat dorsal dentate gyrus

2017 ◽  
Vol 27 ◽  
pp. S1013-S1014
Author(s):  
N.D. Alves ◽  
P. Patrício ◽  
J.S. Correia ◽  
A. Mateus-Pinheiro ◽  
A.R. Machado-Santos ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Chronic Stress ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Pneumococcal Cell Wall-Induced Meningitis Impairs Adult Hippocampal Neurogenesis

2007 ◽  
Vol 75 (9) ◽  
pp. 4289-4297 ◽  
Author(s):  
Olaf Hoffmann ◽  
Cordula Mahrhofer ◽  
Nina Rueter ◽  
Dorette Freyer ◽  
Bettina Bert ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Neuronal Degeneration ◽  
Continuous Process ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
High Rate ◽  
Induction Treatment ◽  
The Impact

ABSTRACT Bacterial meningitis is a major infectious cause of neuronal degeneration in the hippocampus. Neurogenesis, a continuous process in the adult hippocampus, could ameliorate such loss. Yet the high rate of sequelae from meningitis suggests that this repair mechanism is inefficient. Here we used a mouse model of nonreplicative bacterial meningitis to determine the impact of transient intracranial inflammation on adult neurogenesis. Experimental meningitis resulted in a net loss of neurons, diminished volume, and impaired neurogenesis in the dentate gyrus for weeks following recovery from the insult. Inducible nitric oxide synthase (iNOS) immunoreactivity was prominent in microglia in nonproliferating areas of the dentate gyrus and hilus region after meningitis induction. Treatment with the specific iNOS inhibitor N6-(1-iminoethyl)-l-lysine restored neurogenesis in experimental meningitis. These data suggest that local central nervous system inflammation in and of itself suppresses adult neurogenesis by affecting both proliferation and neuronal differentiation. Repair of cognitive dysfunction following meningitis could be improved by intervention to interrupt these actively suppressive effects.

scholarly journals Bilateral Hippocampal Volume Increase in Patients with Bipolar Disorder and Short-term Lithium Treatment

2007 ◽  
Vol 33 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Kaan Yucel ◽  
Valerie H Taylor ◽  
Margaret C McKinnon ◽  
Kathryn MacDonald ◽  
Martin Alda ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Lithium Treatment ◽  
Hippocampal Volume ◽  
Short Term ◽  
Volume Increase

scholarly journals Vangl2, a core component of the WNT/PCP pathway, regulates adult hippocampal neurogenesis and age-related decline in cognitive flexibility

2021 ◽  
Author(s):  
M Koehl ◽  
E Ladevèze ◽  
M Montcouquiol ◽  
DN Abrous
Keyword(s):  
Episodic Memory ◽  
Dentate Gyrus ◽  
Cognitive Flexibility ◽  
Adult Neurogenesis ◽  
Continuous Production ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Core Component ◽  
Dominant Negative Mutation ◽  
Age Related

AbstractDecline in episodic memory is one of the hallmarks of aging and represents one of the most important health problems facing western societies. A key structure in episodic memory is the hippocampal formation and the dentate gyrus in particular, as the continuous production of new dentate granule neurons in this brain region was found to play a crucial role in memory and in age-related decline in memory. As such, understanding the molecular processes that regulate the relationship between adult neurogenesis and aging of memory function holds great therapeutic potential. Recently, we found that Vang-gogh like 2 (Vangl2), a core component of the planar cell polarity signaling pathway, is enriched in the dentate gyrus of adult mice. In this context, we sought to evaluate the involvement of this effector of the Wnt/PCP pathway in both adult neurogenesis and memory abilities in adult and middle-aged mice. Using a heterozygous mouse model carrying a dominant negative mutation in Vangl2 gene, we show that alteration in Vangl2 expression decreases the survival of adult-born granule cells and advances the onset of decrease in cognitive flexibility. Inability of mutant mice to erase old irrelevant information to the benefit of new relevant ones highlights a key role of Vangl2 in interference-based forgetting. Taken together, our findings show for the first that Vangl2 activity may constitute an interesting target to prevent age-related decline in hippocampal plasticity and memory.

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