scholarly journals Stable Adult Hippocampal Neurogenesis in Cannabinoid Receptor CB2 Deficient Mice

2019 ◽  
Vol 20 (15) ◽  
pp. 3759 ◽  
Author(s):  
Leonore Mensching ◽  
Nevena Djogo ◽  
Christina Keller ◽  
Sebastian Rading ◽  
Meliha Karsak
Keyword(s):  
Adult Neurogenesis ◽  
Cannabinoid Receptor ◽  
Hippocampal Neurogenesis ◽  
Neural Progenitors ◽  
Adult Hippocampal Neurogenesis ◽  
Double Positive ◽  
Cannabinoid Receptor 2 ◽  
Immature Neuron ◽  
G Protein Coupled ◽  
Deficient Mice

The G-protein coupled cannabinoid receptor 2 (CB2) has been implicated in the regulation of adult neurogenesis in the hippocampus. The contribution of CB2 towards basal levels of proliferation and the number of neural progenitors in the subgranular zone (SGZ) of the dentate gyrus, however, remain unclear. We stained hippocampal brain sections of 16- to 17-week-old wildtype and CB2-deficient mice, for neural progenitor and immature neuron markers doublecortin (DCX) and calretinin (CR) and for the proliferation marker Ki67 and quantified the number of positive cells in the SGZ. The quantification revealed that CB2 deficiency neither altered overall cell proliferation nor the size of the DCX+ or DCX and CR double-positive populations in the SGZ compared to control animals. The results indicate that CB2 might not contribute to basal levels of adult neurogenesis in four-month-old healthy mice. CB2 signaling might be more relevant in conditions where adult neurogenesis is dynamically regulated, such as neuroinflammation.

scholarly journals Cnr2 Deficiency Confers Resistance to Inflammation-Induced Preterm Birth in Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 4006-4014 ◽  
Author(s):  
Xiaofei Sun ◽  
Monica Cappelletti ◽  
Yingju Li ◽  
Christopher L. Karp ◽  
Senad Divanovic ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Cannabinoid Receptor ◽  
Serum Levels ◽  
Camp Accumulation ◽  
Serum Progesterone ◽  
Cannabinoid Receptor 2 ◽  
Lps Challenge ◽  
G Protein Coupled ◽  
Deficient Mice

Abstract Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate immune responses. We show here that Cnr2, but not Cnr1, deficient mice are resistant to lipopolysaccharide (LPS)-driven preterm birth and suppression of serum progesterone levels. After LPS challenge, Cnr2−/− mice exhibited increased serum levels of IL-10 with decreased IL-6 levels. These changes were associated with reduced LPS-induced Ptgs2 expression at the maternal-conceptus interface on day 16 of pregnancy. LPS stimulation of Cnr2−/− dendritic cells in vitro resulted in increased IL-10 with reduced IL-6 production and correlated with increased cAMP accumulation. Collectively, our results suggest that increased IL-10 production occurring via augmented cAMP accumulation represents a potential mechanism for the resistance of Cnr2−/− mice to LPS-induced preterm birth. These results may have clinical relevance, because currently, there are limited options to prevent preterm birth.

scholarly journals A non-linear relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin

2020 ◽  
Author(s):  
Indira Mendez-David ◽  
Denis J David ◽  
Claudine Deloménie ◽  
Jean-Martin Beaulieu ◽  
Alain M. Gardier ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chronic Stress ◽  
Granule Cells ◽  
Antidepressant Treatment ◽  
Hippocampal Neurogenesis ◽  
Neural Progenitors ◽  
Adult Hippocampal Neurogenesis ◽  
List Type ◽  
Stress Model ◽  
Immature Neuron

ABSTRACTWe investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule β2-arrestin is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and on survival of adult-born granule cells are absent in the β2-arrestin knockout (β2-Arr KO) mice. To our surprise fluoxetine induced a dramatic upregulation of doublecortin (DCX) in the β2-Arr KO mice, indicating that DCX expression can be increased even though AHN is not. We discovered two other conditions where DCX expression is regulated non linearly compared to levels of AHN: a chronic stress model where DCX is upregulated and an inflammation model where DCX is down regulated. We conclude that assessing DCX expression alone to quantify levels of AHN can be misleading and that caution should be applied when label retention techniques are not available.HIGHLIGHTSβ2-arrestin (β-Arr2) is required for the antidepressant-like effects of fluoxetine.A dramatic upregulation of doublecortin (DCX) is observed in the β2-Arr KO mice after antidepressant treatment whereas its effects on proliferation of neural progenitors and on survival of adult-born granule cells are absent.DCX is more upregulated than the number of young neurons in a mouse model of depression.DCX is more down regulated than the number of young neurons in a model of inflammation.microRNAs (miRs) may contribute to the regulation of DCX mRNA expression.

scholarly journals Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

2021 ◽  
Vol 22 (14) ◽  
pp. 7339
Author(s):  
Julia Leschik ◽  
Beat Lutz ◽  
Antonietta Gentile
Keyword(s):  
Major Depression ◽  
Adult Neurogenesis ◽  
Current Knowledge ◽  
Functional Relation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Special Focus ◽  
Extrinsic Cues ◽  
Health And Disease ◽  
Newborn Neurons

Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.

scholarly journals Does Impairment of Adult Neurogenesis Contribute to Pathophysiology of Alzheimer's Disease? A Still Open Question

2021 ◽  
Vol 13 ◽  
Author(s):  
Domenica Donatella Li Puma ◽  
Roberto Piacentini ◽  
Claudio Grassi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Adult Neurogenesis ◽  
Memory Formation ◽  
Hippocampal Neurogenesis ◽  
Synaptic Function ◽  
Adult Hippocampal Neurogenesis ◽  
Amyloid Β Protein

Adult hippocampal neurogenesis is a physiological mechanism contributing to hippocampal memory formation. Several studies associated altered hippocampal neurogenesis with aging and Alzheimer's disease (AD). However, whether amyloid-β protein (Aβ)/tau accumulation impairs adult hippocampal neurogenesis and, consequently, the hippocampal circuitry, involved in memory formation, or altered neurogenesis is an epiphenomenon of AD neuropathology contributing negligibly to the AD phenotype, is, especially in humans, still debated. The detrimental effects of Aβ/tau on synaptic function and neuronal viability have been clearly addressed both in in vitro and in vivo experimental models. Until some years ago, studies carried out on in vitro models investigating the action of Aβ/tau on proliferation and differentiation of hippocampal neural stem cells led to contrasting results, mainly due to discrepancies arising from different experimental conditions (e.g., different cellular/animal models, different Aβ and/or tau isoforms, concentrations, and/or aggregation profiles). To date, studies investigating in situ adult hippocampal neurogenesis indicate severe impairment in most of transgenic AD mice; this impairment precedes by several months cognitive dysfunction. Using experimental tools, which only became available in the last few years, research in humans indicated that hippocampal neurogenesis is altered in cognitive declined individuals affected by either mild cognitive impairment or AD as well as in normal cognitive elderly with a significant inverse relationship between the number of newly formed neurons and cognitive impairment. However, despite that such information is available, the question whether impaired neurogenesis contributes to AD pathogenesis or is a mere consequence of Aβ/pTau accumulation is not definitively answered. Herein, we attempted to shed light on this complex and very intriguing topic by reviewing relevant literature on impairment of adult neurogenesis in mouse models of AD and in AD patients analyzing the temporal relationship between the occurrence of altered neurogenesis and the appearance of AD hallmarks and cognitive dysfunctions.

scholarly journals Acute Ethanol Inhibition of Adult Hippocampal Neurogenesis Involves CB1 Cannabinoid Receptor Signaling

2018 ◽  
Vol 42 (4) ◽  
pp. 718-726 ◽  
Author(s):  
Dal Khatri ◽  
Genevieve Laroche ◽  
Marion L. Grant ◽  
Victoria M. Jones ◽  
Ryan P. Vetreno ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Receptor Signaling ◽  
Ethanol Inhibition ◽  
Cb1 Cannabinoid Receptor ◽  
Acute Ethanol

scholarly journals The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis

2020 ◽  
Vol 29 (12) ◽  
pp. 1950-1968
Author(s):  
Charlotte Castillon ◽  
Laurine Gonzalez ◽  
Florence Domenichini ◽  
Sandrine Guyon ◽  
Kevin Da Silva ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Spatial Memory ◽  
Adult Neurogenesis ◽  
Hippocampal Neurons ◽  
Memory Task ◽  
Clinical Signs ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Adult Born Neurons

Abstract The link between mutations associated with intellectual disability (ID) and the mechanisms underlying cognitive dysfunctions remains largely unknown. Here, we focused on PAK3, a serine/threonine kinase whose gene mutations cause X-linked ID. We generated a new mutant mouse model bearing the missense R67C mutation of the Pak3 gene (Pak3-R67C), known to cause moderate to severe ID in humans without other clinical signs and investigated hippocampal-dependent memory and adult hippocampal neurogenesis. Adult male Pak3-R67C mice exhibited selective impairments in long-term spatial memory and pattern separation function, suggestive of altered hippocampal neurogenesis. A delayed non-matching to place paradigm testing memory flexibility and proactive interference, reported here as being adult neurogenesis-dependent, revealed a hypersensitivity to high interference in Pak3-R67C mice. Analyzing adult hippocampal neurogenesis in Pak3-R67C mice reveals no alteration in the first steps of adult neurogenesis, but an accelerated death of a population of adult-born neurons during the critical period of 18–28 days after their birth. We then investigated the recruitment of hippocampal adult-born neurons after spatial memory recall. Post-recall activation of mature dentate granule cells in Pak3-R67C mice was unaffected, but a complete failure of activation of young DCX + newborn neurons was found, suggesting they were not recruited during the memory task. Decreased expression of the KCC2b chloride cotransporter and altered dendritic development indicate that young adult-born neurons are not fully functional in Pak3-R67C mice. We suggest that these defects in the dynamics and learning-associated recruitment of newborn hippocampal neurons may contribute to the selective cognitive deficits observed in this mouse model of ID.

scholarly journals Adult Hippocampal Neurogenesis in Different Taxonomic Groups: Possible Functional Similarities and Striking Controversies

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 125 ◽  
Author(s):  
Marcus Augusto-Oliveira ◽  
Gabriela Arrifano ◽  
João Malva ◽  
Maria Crespo-Lopez
Keyword(s):  
Cognitive Processes ◽  
Adult Neurogenesis ◽  
Spatial Navigation ◽  
Absolute Number ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Consolidation Process ◽  
Apparent Reduction ◽  
Taxonomic Groups ◽  
Intense Debate

Adult neurogenesis occurs in many species, from fish to mammals, with an apparent reduction in the number of both neurogenic zones and new neurons inserted into established circuits with increasing brain complexity. Although the absolute number of new neurons is high in some species, the ratio of these cells to those already existing in the circuit is low. Continuous replacement/addition plays a role in spatial navigation (migration) and other cognitive processes in birds and rodents, but none of the literature relates adult neurogenesis to spatial navigation and memory in primates and humans. Some models developed by computational neuroscience attribute a high weight to hippocampal adult neurogenesis in learning and memory processes, with greater relevance to pattern separation. In contrast to theories involving neurogenesis in cognitive processes, absence/rarity of neurogenesis in the hippocampus of primates and adult humans was recently suggested and is under intense debate. Although the learning process is supported by plasticity, the retention of memories requires a certain degree of consolidated circuitry structures, otherwise the consolidation process would be hampered. Here, we compare and discuss hippocampal adult neurogenesis in different species and the inherent paradoxical aspects.

scholarly journals Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis

2010 ◽  
Vol 13 (2) ◽  
pp. 191-205 ◽  
Author(s):  
Francisco Alén ◽  
Aurélie Mouret ◽  
Maria-Paz Viveros ◽  
Ricardo Llorente ◽  
Gabriel Lepousez ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Cannabinoid Receptor ◽  
Receptor Activation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise

2017 ◽  
Vol 28 (7) ◽  
pp. 693-703 ◽  
Author(s):  
Lina Sun ◽  
Qingshan Sun ◽  
Jinshun Qi
Keyword(s):  
Adult Neurogenesis ◽  
Healthy Lifestyle ◽  
Brain Plasticity ◽  
Treatment Method ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Brain Functions ◽  
Antidepressant Effects ◽  
Exercise Activity ◽  
The Brain

AbstractDepression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

scholarly journals Running Promotes Spatial Bias Independently of Adult Neurogenesis

2017 ◽  
Author(s):  
Jason S. Snyder ◽  
Shaina P. Cahill ◽  
Paul W. Frankland
Keyword(s):  
Adult Neurogenesis ◽  
Dorsal Striatum ◽  
Memory Systems ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Response Strategy ◽  
Response Strategies ◽  
Spatial Strategies ◽  
Conflict Situations ◽  
Exercise Induced

ABSTRACTDifferent memory systems offer distinct advantages to navigational behavior. The hippocampus forms complex associations between environmental stimuli, enabling flexible navigation through space. In contrast, the dorsal striatum associates discrete cues and favorable behavioral responses, enabling habit-like, automated navigation. While these two systems often complement one another, there are instances where striatal-dependent responses (e.g. approach a cue) conflict with hippocampal representations of spatial goals. In conflict situations, preference for spatial vs. response strategies varies across individuals and depends on previous experience, plasticity and the integrity of these two memory systems. Here, we investigated the role of adult hippocampal neurogenesis and exercise on mouse search strategies in a water maze task that can be solved with either a hippocampal-dependent place strategy or a striatal-dependent cue-response strategy. We predicted that inhibiting adult neurogenesis would impair hippocampal function and shift behavior towards striatal-dependent cue responses. However, blocking neurogenesis in a transgenic nestin-TK mouse did not affect strategy choice. We then investigated whether a pro-neurogenic stimulus, running, would bias mice towards hippocampal-dependent spatial strategies. While running indeed promoted spatial strategies, it did so even when neurogenesis was inhibited in nestin-TK mice. These findings indicate that exercise-induced increases in neurogenesis are not always required for enhanced cognitive function. Furthermore, our data identify exercise as a potentially useful strategy for promoting flexible, cognitive forms of memory in habit-related disorders that are characterized by excessive responding to discrete cues.

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