Hemin Feng

All Publications

• Cholecystokinin B receptor agonists alleviates anterograde amnesia in cholecystokinin-deficient and aged Alzheimer's disease mice. Alzheimer's research & therapy Zhang, N., Sui, Y., Jendrichovsky, P., Feng, H., Shi, H., Zhang, X., Xu, S., Sun, W., Zhang, H., Chen, X., Tortorella, M. D., He, J. 2024; 16 (1): 109

  Abstract

  As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD.mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK-/-) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation.Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK-/- mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists.Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.

  View details for DOI 10.1186/s13195-024-01472-1

  View details for PubMedID 38750512

  View details for PubMedCentralID PMC11094875

• Cholecystokinin B receptor antagonists for the treatment of depression via blocking long-term potentiation in the basolateral amygdala. Molecular psychiatry Zhang, X., Asim, M., Fang, W., Md Monir, H., Wang, H., Kim, K., Feng, H., Wang, S., Gao, Q., Lai, Y., He, J. 2023

  Abstract

  Depression is a common and severe mental disorder. Evidence suggested a substantial causal relationship between stressful life events and the onset of episodes of major depression. However, the stress-induced pathogenesis of depression and the related neural circuitry is poorly understood. Here, we investigated how cholecystokinin (CCK) and CCKBR in the basolateral amygdala (BLA) are implicated in stress-mediated depressive-like behavior. The BLA mediates emotional memories, and long-term potentiation (LTP) is widely considered a trace of memory. We identified that the cholecystokinin knockout (CCK-KO) mice impaired LTP in the BLA, while the application of CCK4 induced LTP after low-frequency stimulation (LFS). The entorhinal cortex (EC) CCK neurons project to the BLA and optogenetic activation of EC CCK afferents to BLA-promoted stress susceptibility through the release of CCK. We demonstrated that EC CCK neurons innervate CCKBR cells in the BLA and CCK-B receptor knockout (CCKBR-KO) mice impaired LTP in the BLA. Moreover, the CCKBR antagonists also blocked high-frequency stimulation (HFS) induced LTP formation in the BLA. Notably, CCKBR antagonists infusion into the BLA displayed an antidepressant-like effect in the chronic social defeat stress model. Together, these results indicate that CCKBR could be a potential target to treat depression.

  View details for DOI 10.1038/s41380-023-02127-7

  View details for PubMedID 37365241

  View details for PubMedCentralID 8813060