Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation

Geng, Xin; Wang, Meng; Leng, Yunjun; Li, Lin; Yang, Haiyuan; Dai, Yifan; Wang, Ying

doi:10.7555/jbr.35.20210107

Cited by 4 publications

(4 citation statements)

References 47 publications

(44 reference statements)

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“…Thus, slices and tissues from mPFC and striatum were prepared 6 h after the last alcohol exposure to detect neuron injury. Our results showed that nissl bodies from mPFC and striatum decreased in alcohol group [33], and knocking out of NLRP3 alleviated the damage of Nissl bodies caused by binge drinking (Fig. 3A).…”

Section: Nlrp3 De Ciency Decreases Binge Drinking-induced Anxiety-lik...mentioning

confidence: 64%

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in mPFC-striatal circuits

Vidjro

Guo

et al. 2022

Preprint

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Background Repeated binge alcohol drinking and chronic alcohol consumption with negative effects such as anxiety on cessation induces alcohol use disorders. This process is associated with activation of NLRP3 inflammasome-mediated responses. However, whether and how inhibition of NLRP3 inflammasome alters alcohol intake and anxiety behavior remains unclear. Methods A combination of drinking-in-the dark and Gavage model were established in NLRP3-knockout and their control mice. Behaviors were assessed by open-field and elevated plus maze tests. Binge alcohol drinking at 2h and 4h were measured and 24 voluntary drinking was determined by a two-bottle choice paradigm. Western blot and ELISA were applied to examine the levels of NLRP3 inflammasome and inflammatory factors such as IL-1β and TNF-α. Nissl’s staining was measured the neuronal injury. Electrophysiological method was determined the glutamatergic transmission in mPFC to striatum circuits. In vivo opotogenetic LTP and LTD were applied to control the function of mPFC-striatal circuits on behavior of mice. MCC950 was used to antagonize NLRP3 inflammasome. Results The binge alcohol intake was decreased in NLRP3 KO mice compared to their control drinking mice. During alcohol withdrawal, NLRP3 deficiency attenuated anxiety-like behaviors and neuronal injury in mPFC and striatum. Moreover, we discovered that the glutamatergic transmission from cortex to striatum was reduced in NLRP3 KO mice. Importantly, in vivo optogenetic induction of long-term potentiation (LTP) of mPFC-striatal circuits reversed the effects of NLRP3 deficiency on glutamatergic transmission and anxiety behaviors. We also demonstrated that optogenetic induction of LTD decreased anxiety-like behaviors with a reduction of glutamatergic transmission. Interestingly, NLRP3 deficiency or inhibition (MCC950 injection)-mediated the attenuation of anxiety behavior reduced binge alcohol intake, but did not decrease 24h-voluntary alcohol consumption and alcohol preference. Conclusion Our results demonstrate that NLRP3 deficiency decreases binge alcohol intake and anxiety-like behaviors through downregulation of glutamatergic transmission in mPFC-striatal circuits, which may provide an anti-inflammatory target to treat alcohol use disorders.

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Section: Nlrp3 De Ciency Decreases Binge Drinking-induced Anxiety-lik...mentioning

confidence: 64%

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in mPFC-striatal circuits

Vidjro

Guo

et al. 2022

Preprint

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“…1d). It is well established that HIBD impairs spatial learning and memory [23]. The Morris water maze was adopted to assess the spatial learning performance, which revealed that mfat-1 HIBD mice spent less time finding the hidden platform underneath the water than their WT counterparts during the acquisition and training phase, as exhibited by swimming distance and escape latency values in the experiments (Fig.…”

Section: Mfat-1 Mice Partially Reversed Hibd-induced Neurological Dys...mentioning

confidence: 93%

“…S7. The male mice aged between 6 and 8 weeks were used to establish the HIBD experimental model as previously reported [23]. In brief, the mice were positioned supine in a surgical stereomicroscope (Nikon) under induction and maintenance of 1-2 vol.% isoflurane (RWD Life Science) anesthesia.…”

Section: Hibd Mouse Experimental Model and Nds Determinationmentioning

confidence: 99%

Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood–brain barrier in mfat-1 transgenic mice

Zhang

Chang

et al. 2023

Cell. Mol. Life Sci.

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Previous studies have shown that mfat-1 transgenic mice have protective effects against some central nervous system (CNS) disorders, owing to the high docosahexaenoic acid (DHA) content enriched in their brains. However, whether this protective effect is connected to the blood–brain barrier (BBB) remains unclear. This study aims to investigate the mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. mfat-1 mice not only demonstrated a significant amelioration of neurological dysfunction and neuronal damage but also partly maintained the physiological permeability of the BBB after HIBD. We initially showed this was associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB, resulting from more lysophosphatidylcholine (LPC)-DHA entering the brain. Wild-type (WT) mice showed a similar Mfsd2a expression trend after long-term feeding with an LPC-DHA-rich diet. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. HIBD-induced BBB high permeability was attenuated by Mfsd2a, primarily through a transcellular pathway to decrease caveolae-like vesicle-mediated transcytosis. Taken together, these findings not only reveal that mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the severity of HIBD, but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.

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“…The male mice aged between 6 to 8 weeks were used to establish the HIBD experimental model as previously reported [23]. In brief, the mice were positioned supine in a surgical stereomicroscope (Nikon) under induction and maintenance of 1-2 vol.% isoflurane (RWD Life Science) anesthesia.…”

Section: Hibd Mouse Experimental Model and Nds Determinationmentioning

confidence: 99%

Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood-brain barrier in mfat-1 transgenic mice

Zhang

Chang

et al. 2022

Preprint

View full text Add to dashboard Cite

Previous studies have shown that mfat-1 transgenic mice have protective effects against certain central nervous system (CNS) disorders, mainly through the high docosahexaenoic acid (DHA) content enriched in the brain without mentioning the blood - brain barrier (BBB). This study aimed to investigate the underlying mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. We first found the mfat-1 mice showed a significant amelioration of neurological dysfunction and neuronal damage associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB after HIBD. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. Mfsd2a attenuated BBB high-permeability caused by HIBD through inhibiting caveolae-like vesicles-mediated transcytosis. Taken together, these results not only reveal mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the degree of HIBD but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.

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Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation

Cited by 4 publications

References 47 publications

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in mPFC-striatal circuits

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in mPFC-striatal circuits

Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood–brain barrier in mfat-1 transgenic mice

Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood-brain barrier in mfat-1 transgenic mice

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