Biology subjects

Na, A. Y.

Publications and source records attributed to Na, A. Y..

3 recordsLinked to original sources

bioRxiv2025

Inactivation of NMDAR and CaMKII signaling within the prelimbic cortex blocks incubated cocaine- and sucrose-craving

The incubation of craving is a term coined to characterize the behavioral phenomenon wherein cue-elicited craving strengthens over a period of abstinence. Incubated cocaine-craving is mediated, at least in part, by increased glutamate release within the prelimbic cortex (PL). We hypothesized that this glutamate release stimulates NMDA-type glutamate receptors (NMDARs) leading to calcium-dependent activation of CaMKII signaling that drives incubated craving. To test this hypothesis, adult male and female Sprague-Dawley rats were trained to self-administer either IV cocaine or sucrose pellets (6h/day x10 days) and tested for cue-elicited cocaine- or sucrose-craving in early versus later (i.e. after incubation) withdrawal. Incubated cocaine-seeking was associated with increased CaMKII activity in the PL, but no change in NMDAR subunits. In contrast, incubated sucrose-craving was associated with many sex-dependent changes in both NMDAR subunit expression and CaMKII activation that were subregion-selective. An intra-PL infusion of the NMDA antagonist D-AP5 (2.5 or 7.5 {micro}g/side) or the CaMKII inhibitor myr-AIP (10 pg/side) blocked both incubated cocaine- and sucrose-craving, with no effects detected in early withdrawal. Co-infusion of both D-AP5 and myr-AIP exerted an additive effect on incubated cocaine-craving that was larger than either antagonist alone. These data corroborate earlier evidence for distinct biochemical correlates within mPFC between incubated cocaine- and sucrose-craving and, for the first time, demonstrate that NMDARs and CaMKII activation within the PL are common drivers of incubated craving that operate via independent signaling pathways suggesting combined pharmacological treatments may have greater efficacy in managing addiction.

neuroscience↗

bioRxiv2025

AMPA receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving

The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). To investigate the role of mPFC AMPARs in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPAR antagonist NBQX (0 or 1 {micro}g/0.5 {micro}l per side), followed by 30-min tests for cue-reinforced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine- and sucrose-craving to AMPAR subunit expression within mPFC subregions. Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving. Together, these findings indicate a necessary role for AMPARs within the PL in driving incubated cocaine-craving and suggest that AMPARs located within the IL may be involved also in sucrose-craving selectively in males.

neuroscience↗

bioRxiv2021

SIRT5 is the desuccinylase of LDHA as novel cancer metastatic stimulator in aggressive prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Among patients who developed advanced PCa, 80% suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the details of the mechanisms underlying castration-resistant PCa (CRPC) remains unclear. SIRT5, an NAD+-dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we showed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patients survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase of lysine 118 succinylation (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study investigated the reduction of SIRT5 and LDHA-K118su as a novel mechanism involved in PCa progression. It can also be proposed as a new target that can prevent castration-resistant PCa progression, which is key to PCa treatment.

cancer biology↗