adult neurogenesis
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2022 ◽  
Vol 2022 ◽  
pp. 1-18
Author(s):  
Stefano Farioli-Vecchioli ◽  
Valentina Ricci ◽  
Silvia Middei

The mammalian hippocampal dentate gyrus is a niche for adult neurogenesis from neural stem cells. Newborn neurons integrate into existing neuronal networks, where they play a key role in hippocampal functions, including learning and memory. In the ageing brain, neurogenic capability progressively declines while in parallel increases the risk for developing Alzheimer’s disease (AD), the main neurodegenerative disorder associated with memory loss. Numerous studies have investigated whether impaired adult neurogenesis contributes to memory decline in AD. Here, we review the literature on adult hippocampal neurogenesis (AHN) and AD by focusing on both human and mouse model studies. First, we describe key steps of AHN, report recent evidence of this phenomenon in humans, and describe the specific contribution of newborn neurons to memory, as evinced by animal studies. Next, we review articles investigating AHN in AD patients and critically examine the discrepancies among different studies over the last two decades. Also, we summarize researches investigating AHN in AD mouse models, and from these studies, we extrapolate the contribution of molecular factors linking AD-related changes to impaired neurogenesis. Lastly, we examine animal studies that link impaired neurogenesis to specific memory dysfunctions in AD and review treatments that have the potential to rescue memory capacities in AD by stimulating AHN.


2022 ◽  
Vol 7 (4) ◽  
pp. 275-280
Author(s):  
Mamata Mishra ◽  
Pankaj Seth

During aging, the decrease of cognitive ability is believed to be the cause of age related neuronal damage and reduced proliferation and differentiation of adult-born neural precursor cells. To modulate the synaptic plasticity and adult neurogenesis, it is of immense importance to enhance the potential of resident neural stem cells of hippocampus and sub ventricular zone (SVZ). The necessity to restore brain functions is enormous in the neurodegenerative disease like Alzheimer, Parkinson diseases, stress induced cognitive dysfunction, depression and age-associated and HIV-associated dementia. As a pioneer transmitter, Gamma Amino Butaric Acid (GABA) influences the activity dependent adult neurogenesis and excites immature neurons in adult hippocampus. GABA holds the key for making adult immature neuron to mature functional neuron hence plays critical role in adult neurogenesis.This review aims to discuss about the spatio-temporal expression of various subunit of GABA-A receptor and how these subunits intimately modulates the synaptic plasticity. During developmental period GABAergic neurons mature at early stages and regulate overall neural activity much before the activity of glutamate. Not only during development but also during adult neurogenesis GABA plays a significant role in neurite outgrowth and establishing well network.


2022 ◽  
Author(s):  
Muhammad Nauman Arshad ◽  
Simon Oppenheimer ◽  
Jaye Jeong ◽  
Bilge Buyukdemirtas ◽  
Janice R Naegele

GABAergic interneurons within the dentate gyrus of the hippocampus regulate adult neurogenesis, including proliferation, migration, and maturation of new granule cells born in the subgranular zone (SGZ) of the dentate gyrus (DG). In temporal lobe epilepsy (TLE), some adult-born granule cells migrate ectopically into the hilus, and these cells contribute to increased hyperexcitability and seizures. Yet, transplanting embryonic day 13.5 fetal mouse medial ganglionic eminence (MGE) GABAergic progenitors into the hippocampus of mice with TLE ameliorates spontaneous seizures, due in part, to increased postsynaptic inhibition of adult-born granule cells. Here, we asked whether MGE progenitor transplantation affects earlier stages of adult neurogenesis, by comparing patterns of neurogenesis in naive mice and epileptic (TLE) mice, with or without MGE transplants. In naive and TLE mice, transplanted MGE cells showed comparable migration and process outgrowth. However, in TLE mice with MGE transplants, fewer adult-born Type 3 progenitors migrated ectopically. Furthermore, more Type 3 progenitors survived and migrated into the granule cell layer (GCL), as determined by immunostaining for doublecortin or the thymidine analogue, bromodeoxyuridine (BrdU). To determine whether MGE transplants affected earlier stages of adult neurogenesis, we compared proliferation in the SGZ two-hours after pulse labeling with BrdU in naive vs. TLE mice and found no significant differences. Furthermore, MGE progenitor transplantation had no effect on cell proliferation in the SGZ. Moreover, when compared to naive mice, TLE mice showed increases in inverted Type 1 progenitors and Type 2 progenitors, concomitant with a decrease in the normally oriented radial Type 1 progenitors. Strikingly, these alterations were abrogated by MGE transplantation. Thus, MGE transplants appear to reverse seizure-induced abnormalities in adult neurogenesis by increasing differentiation and radial migration of adult-born granule cell progenitors, outcomes that may ameliorate seizures.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Lena-Louise Schuele ◽  
Britta Schuermann ◽  
Andras Bilkei-Gorzo ◽  
Sara Gorgzadeh ◽  
Andreas Zimmer ◽  
...  

AbstractThe endocannabinoid system modulates adult hippocampal neurogenesis by promoting the proliferation and survival of neural stem and progenitor cells (NSPCs). This is demonstrated by the disruption of adult neurogenesis under two experimental conditions: (1) NSPC-specific deletion of cannabinoid receptors and (2) constitutive deletion of the enzyme diacylglycerol lipase alpha (DAGLa) which produces the endocannabinoid 2-arachidonoylglycerol (2-AG). However, the specific cell types producing 2-AG relevant to neurogenesis remain unknown. Here we sought to identify the cellular source of endocannabinoids in the subgranular zone of the dentate gyrus (DG) in hippocampus, an important neurogenic niche. For this purpose, we used two complementary Cre-deleter mouse strains to delete Dagla either in neurons, or in astroglia and NSPCs. Surprisingly, neurogenesis was not altered in mice bearing a deletion of Dagla in neurons (Syn-Dagla KO), although neurons are the main source for the endocannabinoids in the brain. In contrast, a specific inducible deletion of Dagla in NPSCs and astrocytes (GLAST-CreERT2-Dagla KO) resulted in a strongly impaired neurogenesis with a 50% decrease in proliferation of newborn cells. These results identify Dagla in NSPCs in the DG or in astrocytes as a prominent regulator of adult hippocampal neurogenesis. We also show a reduction of Daglb expression in GLAST-CreERT2-Dagla KO mice, which may have contributed to the neurogenesis phenotype.


2022 ◽  
Vol 17 (6) ◽  
pp. 1257
Author(s):  
RaulR Gainetdinov ◽  
EvgeniyaV Efimova ◽  
NataliiaV Katolikova ◽  
EvgenyV Kanov

2022 ◽  
Vol 17 (7) ◽  
pp. 1491
Author(s):  
Milos Stanojlovic ◽  
Jana Bonsberger ◽  
Franziska Richter

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 135
Author(s):  
Rafał Płatek ◽  
Piotr Rogujski ◽  
Jarosław Mazuryk ◽  
Marta B. Wiśniewska ◽  
Leszek Kaczmarek ◽  
...  

In the adult brain, new neurons are constitutively derived from postnatal neural stem cells/progenitors located in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricles (migrating and differentiating into different subtypes of the inhibitory interneurons of the olfactory bulbs), and the subgranular layer of the hippocampal dentate gyrus. Cyclin D2 knockout (cD2-KO) mice exhibit reduced numbers of new hippocampal neurons; however, the proliferation deficiency and the dysregulation of adult neurogenesis in the SVZ required further investigation. In this report, we characterized the differentiation potential of each subpopulation of the SVZ neural precursors in cD2-KO mice. The number of newly generated cells in the SVZs was significantly decreased in cD2-KO mice compared to wild type mice (WT), and was not accompanied by elevated levels of apoptosis. Although the number of B1-type quiescent precursors (B1q) and the overall B1-type activated precursors (B1a) were not affected in the SVZ neurogenic niche, the number of transit-amplifying progenitors (TaPs) was significantly reduced. Additionally, the subpopulations of calbindin D28k and calretinin interneurons were diminished in the olfactory bulbs of cD2-KO mice. Our results suggest that cyclin D2 might be critical for the proliferation of neural precursors and progenitors in the SVZ—the transition of B1a into TaPs and, thereafter, the production of newly generated interneurons in the olfactory bulbs. Untangling regulators that functionally modulate adult neurogenesis provides a basis for the development of regenerative therapies for injuries and neurodegenerative diseases.


2021 ◽  
Vol 15 ◽  
Author(s):  
Jared J. Schwartzer ◽  
Dolores Garcia-Arocena ◽  
Amanda Jamal ◽  
Ali Izadi ◽  
Rob Willemsen ◽  
...  

Carriers of the fragile X premutation (PM) can develop a variety of early neurological symptoms, including depression, anxiety and cognitive impairment as well as being at risk for developing the late-onset fragile X-associated tremor/ataxia syndrome (FXTAS). The absence of effective treatments for FXTAS underscores the importance of developing efficacious therapies to reduce the neurological symptoms in elderly PM carriers and FXTAS patients. A recent preliminary study reported that weekly infusions of Allopregnanolone (Allop) may improve deficits in executive function, learning and memory in FXTAS patients. Based on this study we examined whether Allop would improve neurological function in the aged CGG knock-in (CGG KI) dutch mouse, B6.129P2(Cg)-Fmr1tm2Cgr/Cgr, that models much of the symptomatology in PM carriers and FXTAS patients. Wild type and CGG KI mice received 10 weekly injections of Allop (10 mg/kg, s.c.), followed by a battery of behavioral tests of motor function, anxiety, and repetitive behavior, and 5-bromo-2′-deoxyuridine (BrdU) labeling to examine adult neurogenesis. The results provided evidence that Allop in CGG KI mice normalized motor performance and reduced thigmotaxis in the open field, normalized repetitive digging behavior in the marble burying test, but did not appear to increase adult neurogenesis in the hippocampus. Considered together, these results support further examination of Allop as a therapeutic strategy in patients with FXTAS.


2021 ◽  
pp. 100191
Author(s):  
Krishnapriya ◽  
Parameswaran Sasikumar ◽  
Maniyamma Aswathy ◽  
Tripathi Prem Prakash ◽  
Kokkuvayil Vasu Radhakrishnan ◽  
...  

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