scholarly journals Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Amanda Sierra ◽  
Sol Beccari ◽  
Irune Diaz-Aparicio ◽  
Juan M. Encinas ◽  
Samuel Comeau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Trophic Factors ◽  
Normal Brain ◽  
Positive Contribution ◽  
Brain Functions ◽  
Wide Range ◽  
Trauma Injury

Microglia cells are the major orchestrator of the brain inflammatory response. As such, they are traditionally studied in various contexts of trauma, injury, and disease, where they are well-known for regulating a wide range of physiological processes by their release of proinflammatory cytokines, reactive oxygen species, and trophic factors, among other crucial mediators. In the last few years, however, this classical view of microglia was challenged by a series of discoveries showing their active and positive contribution to normal brain functions. In light of these discoveries, surveillant microglia are now emerging as an important effector of cellular plasticity in the healthy brain, alongside astrocytes and other types of inflammatory cells. Here, we will review the roles of microglia in adult hippocampal neurogenesis and their regulation by inflammation during chronic stress, aging, and neurodegenerative diseases, with a particular emphasis on their underlying molecular mechanisms and their functional consequences for learning and memory.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

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.

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 Enriched Environment Ameliorates Adult Hippocampal Neurogenesis Deficits in Tcf4 Haploinsufficient Mice

2020 ◽  
Author(s):  
Katharina Braun ◽  
Benjamin M. Häberle ◽  
Marie-Theres Wittmann ◽  
Dieter Chichung Lie
Keyword(s):  
Transcription Factor ◽  
Intellectual Disability ◽  
Knockout Mice ◽  
Negative Impact ◽  
Brain Regions ◽  
Nervous System Development ◽  
Hippocampal Neurogenesis ◽  
Enriched Environment ◽  
Adult Hippocampal Neurogenesis ◽  
Wide Range

Abstract Background: Transcription factor 4 (TCF4) has been linked to human neurodevelopmental disorders such as intellectual disability, Pitt-Hopkins Syndrome (PTHS), autism, and schizophrenia. Recent work demonstrated that TCF4 participates in the control of a wide range of neurodevelopmental processes in mammalian nervous system development including neural precursor proliferation, timing of differentiation, migration, dendritogenesis and synapse formation. TCF4 is highly expressed in the adult hippocampal dentate gyrus – one of the few brain regions where neural stem / progenitor cells generate new functional neurons throughout life.Results: We here investigated whether TCF4 haploinsufficiency, which in humans causes non-syndromic forms of intellectual disability and PTHS, affects adult hippocampal neurogenesis, a process that is essential for hippocampal plasticity in rodents and potentially in humans. Young adult Tcf4 heterozygote knockout mice showed a major reduction in the level of adult hippocampal neurogenesis, which was at least in part caused by lower stem/progenitor cell numbers and impaired maturation and survival of adult-generated neurons. Interestingly, housing in an enriched environment was sufficient to enhance maturation and survival of new neurons and to substantially augment neurogenesis levels in Tcf4 heterozygote knockout mice.Conclusion: Haploinsufficiency for the transcription factor TCF4 has been linked to non-syndromic intellectual disability and PTHS. The present findings raise the possibility that TCF4 haploinsufficiency may have a continuous negative impact on hippocampal function by impeding hippocampal neurogenesis and suggest that behavioural stimulation may be harnessed to ameliorate a subset of TCF4 haploinsufficiency associated neural deficits during adulthood.

scholarly journals Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Hongsheng Zhang ◽  
Anupama Sathyamurthy ◽  
Fang Liu ◽  
Lei Li ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Orphan Receptor ◽  
Brain Functions ◽  
Density Lipoprotein Receptor ◽  
Neural Stem Progenitor Cells ◽  
Newborn Neurons

Adult neurogenesis in the hippocampus may represent a form of plasticity in brain functions including mood, learning and memory. However, mechanisms underlying neural stem/progenitor cells (NSPCs) proliferation are not well understood. We found that Agrin, a factor critical for neuromuscular junction formation, is elevated in the hippocampus of mice that are stimulated by enriched environment (EE). Genetic deletion of the Agrn gene in excitatory neurons decreases NSPCs proliferation and increases depressive-like behavior. Low-density lipoprotein receptor-related protein 4 (Lrp4), a receptor for Agrin, is expressed in hippocampal NSPCs and its mutation blocked basal as well as EE-induced NSPCs proliferation and maturation of newborn neurons. Finally, we show that Lrp4 interacts with and activates receptor tyrosine kinase-like orphan receptor 2 (Ror2); and Ror2 mutation impairs NSPCs proliferation. Together, these observations identify a role of Agrin-Lrp4-Ror2 signaling for adult neurogenesis, uncovering previously unexpected functions of Agrin and Lrp4 in the brain.

scholarly journals Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
María Belén Pardi ◽  
Mora Belén Ogando ◽  
Alejandro F Schinder ◽  
Antonia Marin-Burgin
Keyword(s):  
Granule Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Information Encoding ◽  
High Frequencies ◽  
Wide Range ◽  
Mature Neurons ◽  
Different Populations ◽  
Immature Cells ◽  
Two Populations

Adult hippocampal neurogenesis provides the dentate gyrus with heterogeneous populations of granule cells (GC) originated at different times. The contribution of these cells to information encoding is under current investigation. Here, we show that incoming spike trains activate different populations of GC determined by the stimulation frequency and GC age. Immature GC respond to a wider range of stimulus frequencies, whereas mature GC are less responsive at high frequencies. This difference is dictated by feedforward inhibition, which restricts mature GC activation. Yet, the stronger inhibition of mature GC results in a higher temporal fidelity compared to that of immature GC. Thus, hippocampal inputs activate two populations of neurons with variable frequency filters: immature cells, with wide‐range responses, that are reliable transmitters of the incoming frequency, and mature neurons, with narrow frequency response, that are precise at informing the beginning of the stimulus, but with a sparse activity.

scholarly journals Selective increases in inter-individual variability in response to environmental enrichment in female mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Julia C Körholz ◽  
Sara Zocher ◽  
Anna N Grzyb ◽  
Benjamin Morisse ◽  
Alexandra Poetzsch ◽  
...  
Keyword(s):  
Environmental Enrichment ◽  
Specific Activity ◽  
Individual Variability ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Multiple Parameters ◽  
Wide Range ◽  
Suitable Animal Model ◽  
Brain And Behavior ◽  
And Behavior

One manifestation of individualization is a progressively differential response of individuals to the non-shared components of the same environment. Individualization has practical implications in the clinical setting, where subtle differences between patients are often decisive for the success of an intervention, yet there has been no suitable animal model to study its underlying biological mechanisms. Here we show that enriched environment (ENR) can serve as a model of brain individualization. We kept 40 isogenic female C57BL/6JRj mice for 3 months in ENR and compared these mice to an equally sized group of standard-housed control animals, looking at the effects on a wide range of phenotypes in terms of both means and variances. Although ENR influenced multiple parameters and restructured correlation patterns between them, it only increased differences among individuals in traits related to brain and behavior (adult hippocampal neurogenesis, motor cortex thickness, open field and object exploration), in agreement with the hypothesis of a specific activity-dependent development of brain individuality.

Investigating the role of the ghrelin axis in cognitive decline and dementia

2021 ◽  
Author(s):  
◽  
Martina Sassi
Keyword(s):  
Mouse Model ◽  
Cognitive Decline ◽  
Young Animal ◽  
Active Form ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Tg2576 Mouse ◽  
Brain Functions ◽  
Acyl Ghrelin ◽  
The Brain

Ghrelin is a 28-amino acid hormone that is generated in a wide number of tissues. Its active form, acyl-ghrelin is able to bind to its receptor GHS-R and exert a variety of functions. In the brain, acyl-ghrelin has been associated with neuroprotection, improved memory and adult hippocampal neurogenesis (AHN). However, the mechanisms controlling acyl-ghrelin-mediated AHN are still unknown. To elucidate this process, different markers of neurogenesis were assessed in a mouse model in which GHS-R+ neurones were ablated specifically from the rostral DG of the hippocampus (rDG), showing that rDG GHS-R+ neurones are essential for maintaining AHN. Acyl-ghrelin has also been shown to prevents the damage caused by neurodegeneration, at least in young animal models of disease. In this thesis, we demonstrated that in the geriatric Tg2576 mouse model of Alzheimer’s disease, acyl-ghrelin maintained an effect on β-amyloid (Aβ) plaques in the hippocampus, promoting a reduction of the Aβ plaques size in AD-like mouse model compared to WT mice. Collectively, research findings highlight the importance of circulating acyl-ghrelin in the brain. However, ghrelin exists in two distinct forms and acyl-ghrelin can be enzymatically modified to the ‘inactive' unacylated-ghrelin (UAG) by acyl-protein thioesterase 1 (APT1). Preventing APT1 mediated de-acylation and increasing acyl-ghrelin bio-availability may prevent the damage caused by neurodegeneration. Unpublished data from our group suggest that PalmostatinB, an APT1 inhibitor, increases levels of acyl-ghrelin in macrophage cells (that naturally produce ghrelin). Therefore, this and other APT1 inhibitors may be considered possible therapeutic agents for the treatment of cognitive decline and diseases associated with dementia. We confirmed that, among several APT1 inhibitors, PalmostatinB is able to increase the level of acyl-ghrelin in vitro. However, further research is warranted into APT1 inhibitors as a novel therapeutic approach to treating cognitive decline and dementia. Together, the data in this thesis support a role for the ghrelinergic system components in modulating brain functions.

scholarly journals A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Odette Leiter ◽  
Gerd Kempermann ◽  
Tara L. Walker
Keyword(s):  
Immune System ◽  
Adult Neurogenesis ◽  
Immune Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Intrinsic Cues ◽  
Normal Brain Function ◽  
The Brain

Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus—a region crucial for learning and memory.

scholarly journals New Insights Into the Role of Aberrant Hippocampal Neurogenesis in Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Chen ◽  
Fuchao Chen ◽  
Yue Wu ◽  
Benhong Zhou
Keyword(s):  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Future Directions ◽  
The Past ◽  
The Central Nervous System ◽  
Spontaneous Recurrent Seizures ◽  
Patients With Epilepsy

Data accumulated over the past four decades have confirmed that adult hippocampal neurogenesis (HN) plays a key role in the wide spectrum of hippocampal pathology. Epilepsy is a disorder of the central nervous system characterized by spontaneous recurrent seizures. Although neurogenesis in persistent germinative zones is altered in the adult rodent models of epilepsy, the effects of seizure-induced neurogenesis in the epileptic brain, in terms of either a pathological or reparative role, are only beginning to be explored. In this review, we described the most recent advances in neurogenesis in epilepsy and outlooked future directions for neural stem cells (NSCs) and epilepsy-in-a-dish models. We proposed that it may help in refining the underlying molecular mechanisms of epilepsy and improving the therapies and precision medicine for patients with epilepsy.

scholarly journals The activity-dependent transcription factor Npas4 regulates IQSEC3 expression in somatostatin interneurons to mediate anxiety-like behavior

2019 ◽  
Author(s):  
Seungjoon Kim ◽  
Dongseok Park ◽  
Jinhu Kim ◽  
Dongsoo Lee ◽  
Dongwook Kim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Dominant Negative ◽  
Normal Brain ◽  
Gabaergic Synapse ◽  
Iq Motif ◽  
Brain Functions ◽  
Activity Dependent ◽  
Gabaergic Synaptic Transmission

AbstractOrganization of mammalian inhibitory synapses is thought to be crucial for normal brain functions, but the underlying molecular mechanisms have been still incompletely understood. IQSEC3 (IQ motif and Sec7 domain 3) is a guanine nucleotide exchange factor for ADP-ribosylation factor (ARF-GEF) that directly interacts with gephyrin. Here, we show that GABAergic synapse-specific transcription factor, Npas4 (neuronal PAS domain protein 4) directly binds to the promoter of Iqsec3 and regulates its transcription. Strikingly, an enriched environment (EE) induced Npas4 upregulation and concurrently increased IQSEC3 protein levels specifically in mouse CA1 stratum oriens layer somatostatin (SST)-expressing GABAergic interneurons, which are compromised in Npas4-knockout (KO) mice. Moreover, expression of wild-type (WT) IQSEC3, but not a dominant-negative (DN) ARF-GEF–inactive mutant, rescued the decreased GABAergic synaptic transmission in Npas4-deficient SST interneurons. Concurrently, expression of IQSEC3 WT normalized the altered GABAergic synaptic transmission in dendrites, but not soma, of Npas4-deficient CA1 pyramidal neurons. Furthermore, expression of IQSEC3 WT, but not IQSEC3 DN, in SST-expressing interneurons in CA1 SST Npas4-KO mice rescued the altered anxiety-like behavior. Collectively, our results suggest that IQSEC3 is a key GABAergic synapse component that is directed by Npas4 activity- and ARF activity-dependent gene programs in SST-expressing interneurons to orchestrate the functional excitation-to-inhibition balance.

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