FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight

Long, Jingyi; Jiang, Wei; Xia, Haibin; Fu, Junyi; Lü, Ping; Hu, Fei; Feng, Wen-Cai; Sun, Weiwen; Gao, Mei-Mei; Yi, Yong‐Hong; Long, Yong

doi:10.1016/j.neuint.2020.104847

Cited by 9 publications

(7 citation statements)

References 51 publications

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“…Effectively, the daily measurement of food intake showed that Fmr1-Δexon 8 animals eat less than their WT counterparts. Our results are supported by previous work conducted by Long and collaborators [ 43 ]. Indeed, they have recently demonstrated that X fragile protein-deficient mice present decreased agouti-related peptide (AgRP), which is one of the most potent and long-lasting appetite stimulators [ 44 ].…”

Section: Discussionsupporting

confidence: 93%

Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome

Parente

Tonini

Buzzelli

et al. 2022

IJMS

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Fragile X Syndrome (FXS) is the most frequent form of inherited X-linked pathology, associated with an intellectual and developmental disability, and currently considered the first monogenic cause of autism spectrum disorder (ASD). Low levels of total cholesterol reported in the serum of FXS patients, and evidence that FMRP targets a subset of mRNAs encoding proteins of lipid synthesis and transport suggests that the cholesterol metabolism impairments could be involved in FXS. Thus, the aim of the presented work was to investigate the modulations of the cholesterol biosynthetic pathway and its end-products in a recently developed Fmr1-Δexon 8 rat model of FXS. Here, we show that this experimental model mimics what is found in FXS patients, exhibiting a lower serum cholesterol content, accompanied by a reduction in food intake and body weight compared to WT animals. Moreover, alterations of proteins committed to cholesterol synthesis and uptake have been observed in the amygdala, prefrontal cortex and nucleus accumbens. Interestingly, the end-products show a brain region-dependent modulation in Fmr1-Δexon 8 rats. Overall, our results demonstrate that the cholesterol biosynthetic pathway is altered in some brain regions of this preclinical model of FXS. This finding has relevance for future studies to delve deeper into the involvement of this metabolic process in FXS, and thus its possible role as a therapeutic target.

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Section: Discussionsupporting

confidence: 93%

Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome

Parente

Tonini

Buzzelli

et al. 2022

IJMS

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show abstract

“…We next investigated whether the impaired FMRP degradation, and the consequent dysregulation of its granule formation, could affect the translation of its mRNA targets. We first assessed the localization of the Map1b mRNA, a well-known target of FMRP ( 76 , 77 ), with FMRP granules using RNA in situ hybridization (ISH) combined with immunofluorescence staining. Map1b mRNA exhibited a punctated staining pattern that colocalized with FMRP granules ( Fig.…”

Section: Resultsmentioning

confidence: 99%

FMRP Long-Range Transport and Degradation Are Mediated by Dynlrb1 in Sensory Neurons

El-Agamy,

Guillaud,

Kono

et al. 2023

Molecular & Cellular Proteomics

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“…Furthermore, MAP1B-KO mice showed a reduction in feeding and body weight, that correlated with AgRP levels, suggesting that the reduction in feeding behavior seen in FMRP-KO mice may be the result of diminished ARC AgRP mRNA, via upregulation of MAP1B (Long et al, 2020). Another study showed that a single bout of treadmill exercise leads to an acute increase in ARC AgRP neuronal activation in mice, subsequently causing an immediate increase in post-exercise food consumption (Bunner et al, 2020).…”

Section: Discussionmentioning

confidence: 97%

Fasting alters p75NTR and AgRP mRNA expression in rat olfactory bulb and hippocampus

MONGE-SANCHEZ

Montiel‐Herrera

VİLLA

et al. 2023

Journal of Cellular Neuroscience and Oxidative Stress

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Classic non-homeostatic structures involved in food intake regulation are reciprocally influenced by metabolic signals. Orexigenic peptides expressed in the olfactory bulb (OB) and hippocampus (HP) modulate olfactory processing and memory, respectively. Hypothalamic circuits also modulate feeding behavior by activating and releasing Agouti-related peptide (AgRP) in response to orexigenic signals. An adequate response to fasting requires the expression of p75 neurotrophin receptor (p75NTR) in AgRP neurons. The present study aimed to determine whether there is a role for p75NTR and AgRP in the OB and HP on the feeding behavior of fasted rats. A group of fasted rats (FG) was confronted with a decision-making paradigm in a T-maze containing a standard chow pellet (CP), and the same pellet coated with a phenolic-rich avocado paste extract (AVO) on either end; their OB and HP were then analyzed with histological and molecular tools. FG rats had briefer feeding latencies, as compared to control rats fed ad libitum (median latencies: 55.4 vs 191.7 min, p = 0.032). They also had reduced cell counts in both brain structures, as compared to satiated rats. AgRP mRNA was not expressed in the HP of either group, however, it was found in the OB. p75NTR mRNA was expressed in both brain structures of FG rats. These results suggest that contrasting metabolic states (fasted or satiated) motivate different feeding responses, which are influenced by p75NTR and AgRP mRNA expression in non-homeostatic food intake brain structures.

show abstract

FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight

Cited by 9 publications

References 51 publications

Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome

Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome

FMRP Long-Range Transport and Degradation Are Mediated by Dynlrb1 in Sensory Neurons

Fasting alters p75NTR and AgRP mRNA expression in rat olfactory bulb and hippocampus

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