Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis

Kandel, Prasanna; Semerci, Fatih; Mishra, Rachana; Choi, William T.; Bajić, Aleksandar; Baluya, Dodge L.; Ma, Long; Chen, Kevin; Cao, Austin C.; Phongmekhin, Tipwarin; Matinyan, Nick; Jiménez-Panizo, Alba; Chamakuri, Srinivas; Raji, Idris; Chang, Lyra; Fuentes‐Prior, Pablo; MacKenzie, Kevin R.; Benn, Caroline; Estébanez‐Perpiñá, Eva; Venken, Koen J. T.; Moore, David D.; Young, Damian W.; Maletić-Savatić, Mirjana

doi:10.1073/pnas.2023784119

Cited by 33 publications

(32 citation statements)

References 57 publications

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“…These genes included NCOA7 (Nuclear Receptor Coactivator 7), a transcriptional coactivator of ESR1 , and ESRRG , a nuclear receptor that interacts with estrogen-responsive elements in the genome ( Festuccia et al, 2018 ; Lazennec et al, 1997 ). NR2E1 , a recently de-orphanized nuclear receptor that binds oleic acid to regulate neurogenesis ( Kandel et al, 2022 ), is another exciting candidate gene. Additionally, we identified several genes– PDSS2 , XRN2 , RPS27A , TCTE1 , ATP6V1C2 , and GRHL1– that have not previously been linked to the morph differences, but convergent lines of evidence suggest that they may play a role in the evolution of the ZAL2 m supergene.…”

Section: Discussionmentioning

confidence: 99%

Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

Jeong

Baran

Sun

et al. 2022

eLife

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In white-throated sparrows, two alternative morphs differing in plumage and behavior segregate with a large chromosomal rearrangement. As with sex chromosomes such as the mammalian Y, the rearranged version of chromosome two (ZAL2m) is in a near-constant state of heterozygosity, offering opportunities to investigate both degenerative and selective processes during the early evolutionary stages of ‘supergenes.’ Here, we generated, synthesized, and analyzed extensive genome-scale data to better understand the forces shaping the evolution of the ZAL2 and ZAL2m chromosomes in this species. We found that features of ZAL2m are consistent with substantially reduced recombination and low levels of degeneration. We also found evidence that selective sweeps took place both on ZAL2m and its standard counterpart, ZAL2, after the rearrangement event. Signatures of positive selection were associated with allelic bias in gene expression, suggesting that antagonistic selection has operated on gene regulation. Finally, we discovered a region exhibiting long-range haplotypes inside the rearrangement on ZAL2m. These haplotypes appear to have been maintained by balancing selection, retaining genetic diversity within the supergene. Together, our analyses illuminate mechanisms contributing to the evolution of a young chromosomal polymorphism, revealing complex selective processes acting concurrently with genetic degeneration to drive the evolution of supergenes.

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Section: Discussionmentioning

confidence: 99%

Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

Jeong

Baran

Sun

et al. 2022

eLife

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“…Recent evidence shows that OA is the most abundant MUFA in human neural stem/progenitor cells and is necessary for their survival [ 108 ]. TLX (also known as NR2E1) is an orphan nuclear receptor that regulates the self-renewal and proliferation of NPCs [ 109 ].…”

Section: Fatty Acids and Neurogenesismentioning

confidence: 99%

“…OA was found to bind to TLX and to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes. This effect led to an increased proliferation rate of NPCs and their differentiation into neurons [ 108 ]. Nitro fatty acids (NO2-FAs) are naturally occurring compounds generated through the actions of reactive nitrogen species on cellular lipids, mainly PUFAs [ 110 ].…”

Section: Fatty Acids and Neurogenesismentioning

confidence: 99%

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Fatty Acids: A Safe Tool for Improving Neurodevelopmental Alterations in Down Syndrome?

Martı́nez-Cué

Bartesaghi

2022

Nutrients

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The triplication of chromosome 21 causes Down syndrome (DS), a genetic disorder that is characterized by intellectual disability (ID). The causes of ID start in utero, leading to impairments in neurogenesis, and continue into infancy, leading to impairments in dendritogenesis, spinogenesis, and connectivity. These defects are associated with alterations in mitochondrial and metabolic functions and precocious aging, leading to the early development of Alzheimer’s disease. Intense efforts are currently underway, taking advantage of DS mouse models to discover pharmacotherapies for the neurodevelopmental and cognitive deficits of DS. Many treatments that proved effective in mouse models may raise safety concerns over human use, especially at early life stages. Accumulating evidence shows that fatty acids, which are nutrients present in normal diets, exert numerous positive effects on the brain. Here, we review (i) the knowledge obtained from animal models regarding the effects of fatty acids on the brain, by focusing on alterations that are particularly prominent in DS, and (ii) the progress recently made in a DS mouse model, suggesting that fatty acids may indeed represent a useful treatment for DS. This scenario should prompt the scientific community to further explore the potential benefit of fatty acids for people with DS.

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“…The decline of hippocampal neurons is the most pronounced change with age ( 5 ). These changes in hippocampus are closely related to age-related exploration and spatial memory impairment as well as an imbalance of hippocampal messenger receptors ( 6 , 7 ). Therefore, a more in-depth understanding of hippocampus aging is essential for the improvement of treatment and prevention of aging-associated diseases.…”

Section: Introductionmentioning

confidence: 99%

Myristic acid alleviates hippocampal aging correlated with GABAergic signaling

et al. 2022

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Previous studies have shown that myristic acid (MA), a saturated fatty acid, could promote the proliferation and differentiation of neural stem cells in vitro. However, the effect of MA on hippocampal neurons aging has not been reported in vivo. Here we employed 22-month-old naturally aged C57BL/6 mice to evaluate the effect and mechanism of MA on hippocampal aging. First, we examined a decreased exploration and spatial memory ability in aging mice using the open field test and Morris water maze. Consistently, aging mice showed degenerative hippocampal histomorphology by H&E and Nissl staining. In terms of mechanism, imbalance of GABRB2 and GABRA2 expression in aging mice might be involved in hippocampus aging by mRNA high throughput sequencing (mRNA-seq) and immunohistochemistry (IHC) validation. Then, we revealed that MA alleviated the damage of exploration and spatial memory ability and ameliorated degeneration and aging of hippocampal neurons. Meanwhile, MA downregulated GABRB2 and upregulated GABRA2 expression, indicating MA might alleviate hippocampal aging correlated with GABAergic signaling. In conclusion, our findings revealed MA alleviated hippocampal aging correlated with GABAergic signaling, which might provide insight into the treatment of aging-associated diseases.

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Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis

Cited by 33 publications

References 57 publications

Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

Fatty Acids: A Safe Tool for Improving Neurodevelopmental Alterations in Down Syndrome?

Myristic acid alleviates hippocampal aging correlated with GABAergic signaling

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