Anhedonia is frequently observed in Alzheimer's disease (AD) patients and is associated with a higher risk of cognitive decline and dementia, and it potentially serve as preclinical marker and psychopathological risk factor for AD. Current antidepressants show limited efficacy in anhedonia, highlighting a critical unmet medical need. In this study, APP/PS1 mice at 8 months of age exhibited...
bioRxivJune 3, 2026Shuo Yang, Ling-Jun Wang, Yunxiang Sun et al.
preprint
Abstract A deeper understanding of the targets and mechanisms of fast-acting antidepressants, exemplified by ketamine, remains indispensable for better therapeutic strategies and understanding depression. Beyond the canonical neuron-centric NMDAR inhibition hypothesis, brain opioid system and glia-mediated processes are increasingly implicated in ketamine’s antidepressant efficacy, yet their...
bioRxivJune 3, 2026Yanxia Liang, Lingjun Wang, Yajie Li et al.
preprint
Ketamine produces rapid antidepressant effects but is constrained by psychotomimetic properties and abuse potential. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) shows antidepressant-like efficacy without N-methyl-D-aspartate receptor (NMDAR) blockade, yet its upstream targets remain unclear. Here we show that HNK potentiates hippocampal excitatory transmission and reverses...
Natural compounds in plants are often unevenly distributed, and determining the best sampling locations to obtain the most representative results is technically challenging. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can provide the basis for formulating sampling guideline. For a succulent plant sample, ensuring the authenticity and in situ nature of the...
Introduction Differentiating whether plant products are natural or artificial is of great importance in many practical fields, including forensic science, food safety, cosmetics, and fast-moving consumer goods. Information about the topographic distribution of compounds is an important criterion for answering this question. However, of equal importance is the likelihood that topographic spatial...