The expression of m6A enzymes in the hippocampus of diabetic cognitive impairment mice and the possible improvement of YTHDF1

li, Menglin; Zhong, Xiaolin; Zhao, Zhen-Wang; Zeng, Zhao-Lin; Yuan, Qing; Xiao, Xinhua; Zu, Xuyu; Liu, Jinghua

doi:10.1016/j.brainres.2021.147766

Cited by 13 publications

(5 citation statements)

References 79 publications

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“…Surgery was performed using a mice brain stereotactic apparatus (RWD, Shenzhen, China). Microinjection of lentivirus labelled with green uorescent protein (GFP) was administered into the hippocampus of both hemispheres as described in our previous study [19]. The lentivirus used in our study including Lv-METTL14 OE and Lv-YTHDC1 (Table 2), all lentivirus were purchased from Shanghai Jikai Gene Chemical Technology Co., Ltd. Brie y, anesthetized mice were xed on the brain stereotactic apparatus, and small bilateral holes were drilled into the skull following the coordinates (relative to bregma), AP-2.1 mm, ML ± 1.9 mm, DV-2.55 mm from the dura.…”

Section: Stereotactic Injection Of Lentivirus To Hippocampusmentioning

confidence: 99%

METTL14/YTHDC1-Mediated m6A Modification in Hippocampus Improves Pentylenetetrazol-Induced Acute Seizures

Zhong,

Chen,

Wang

et al. 2024

Mol Neurobiol

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Epilepsy is a common neurological disorder which can cause signi cant morbidity and mortality. N6-methyladenosine (m6A), the most common chemical epigenetic modi cation among mRNA post-transcriptional modi cations, implicated in various physiological and pathological processes, but its role in epilepsy is still unknown. Here, we provide strong evidences in support of an association of m6A and its regulatory proteins with epilepsy. Our results indicated that the level of m6A was declined in the hippocampus of pentylenetetrazol (PTZ)-induced seizure mice.Both the seizure-like behaviors and the excessive activation of hippocampal neuron were signi cantly mitigated after the administration of m6A agonist Betaine. Mechanically, we found both the hippocampal m6A methyltransferase METTL14 and recognition protein YTHDC1 were decreased in PTZ kindled mice, which might contribute to the reduced hippocampal m6A level. Additionally, hippocampal-speci c over-expression of METTL14 or YTHDC1 by lentivirus injection could signi cantly ameliorate seizure-like behaviors and prevent the excessive activation of hippocampal neuron in epilepsy mice induced by PTZ injection, which might be due to the normalized hippocampal m6A level. Together, this study identi ed METTL14/YTHDC1-mediated m6A modi cation could participate in seizurelike behaviors, which might provide m6A regulation as a potential and novel therapeutic strategy for epilepsy.

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Section: Stereotactic Injection Of Lentivirus To Hippocampusmentioning

confidence: 99%

METTL14/YTHDC1-Mediated m6A Modification in Hippocampus Improves Pentylenetetrazol-Induced Acute Seizures

Zhong,

Chen,

Wang

et al. 2024

Mol Neurobiol

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“…Impairments of fine motor and cognitive function in young mice exposed to multiple sevoflurane are attributable to a specific decrease in YTHDF1 expression ( 115 ). Overexpression of YTHDF1 ameliorates diabetes-induced cognitive impairment ( 116 ). Additionally, elevated YTHDF2 under persistent light impedes cognitive behavior in mice by perturbing the stability of TrkappaB mRNA ( 117 ).…”

Section: The Roles Of the Ythdf Family In Physiological And Pathologi...mentioning

confidence: 99%

“…Furthermore, the delivery of target genes using viral vectors is also a feasible approach to target YTHDFs. YTHDF1 overexpression therapy can be achieved by injecting adeno-associated virus (AAV)-YTHDF1 into the hippocampus of diabetic cognitively impaired mice ( 116 ). In conclusion, clarifying the limitations of YTHDFs is conducive to better clinical transformation.…”

Section: Limitations and Perspectivesmentioning

confidence: 99%

N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

Chen

Gao

et al. 2023

Front. Immunol.

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As the most abundant and conserved internal modification in eukaryote RNAs, N6-methyladenosine (m6A) is involved in a wide range of physiological and pathological processes. The YT521-B homology (YTH) domain-containing family proteins (YTHDFs), including YTHDF1, YTHDF2, and YTHDF3, are a class of cytoplasmic m6A-binding proteins defined by the vertebrate YTH domain, and exert extensive functions in regulating RNA destiny. Distinct expression patterns of the YTHDF family in specific cell types or developmental stages result in prominent differences in multiple biological processes, such as embryonic development, stem cell fate, fat metabolism, neuromodulation, cardiovascular effect, infection, immunity, and tumorigenesis. The YTHDF family mediates tumor proliferation, metastasis, metabolism, drug resistance, and immunity, and possesses the potential of predictive and therapeutic biomarkers. Here, we mainly summary the structures, roles, and mechanisms of the YTHDF family in physiological and pathological processes, especially in multiple cancers, as well as their current limitations and future considerations. This will provide novel angles for deciphering m6A regulation in a biological system.

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“…The protein expression of YTHDF1, YTHDF3, and WTAP in the hippocampus of STZ group decreased. However, the cognitive impairment of STZ mice significantly improved after YTHDF1 overexpression [ 85 ]. YTHDF1 is a promising therapeutic target for diabetes-induced cognitive dysfunction.…”

Section: M6a Methylation In Other Autoimmune Diseasesmentioning

confidence: 99%

M6A methylation modification in autoimmune diseases, a promising treatment strategy based on epigenetics

Huang,

Xue,

Chang

et al. 2023

Arthritis Res Ther

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Background N6-methyladenosine (m6A) methylation modification is involved in the regulation of various biological processes, including inflammation, antitumor, and antiviral immunity. However, the role of m6A modification in the pathogenesis of autoimmune diseases has been rarely reported. Methods Based on a description of m6A modification and the corresponding research methods, this review systematically summarizes current insights into the mechanism of m6A methylation modification in autoimmune diseases, especially its contribution to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Results By regulating different biological processes, m6A methylation is involved in the pathogenesis of autoimmune diseases and provides a promising biomarker for the diagnosis and treatment of such diseases. Notably, m6A methylation modification is involved in regulating a variety of immune cells and mitochondrial energy metabolism. In addition, m6A methylation modification plays a role in the pathological processes of RA, and m6A methylation-related genes can be used as potential targets in RA therapy. Conclusions M6A methylation modification plays an important role in autoimmune pathological processes such as RA and SLE and represents a promising new target for clinical diagnosis and treatment, providing new ideas for the treatment of autoimmune diseases by targeting m6A modification-related pathways.

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The expression of m6A enzymes in the hippocampus of diabetic cognitive impairment mice and the possible improvement of YTHDF1

Cited by 13 publications

References 79 publications

METTL14/YTHDC1-Mediated m6A Modification in Hippocampus Improves Pentylenetetrazol-Induced Acute Seizures

METTL14/YTHDC1-Mediated m6A Modification in Hippocampus Improves Pentylenetetrazol-Induced Acute Seizures

N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

M6A methylation modification in autoimmune diseases, a promising treatment strategy based on epigenetics

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