Evidence shows that stress can promote the occurrence and development of tumors. In recent years, many studies have shown that stress-related hormones or peripheral neurotransmitters can promote the proliferation, survival, and angiogenesis of tumor cells and impair the body’s immune response, causing tumor cells to escape the “surveillance” of the immune system. However, the perception of stress occurs in the central nervous system (CNS) and the role of the central nervous system in tumor progression is still unclear, as are the underlying mechanisms. This review summarizes what is known of stress-related CNS-network activation during the stress response and the influence of the CNS on tumors and discusses available adjuvant treatment methods for cancer patients with negative emotional states, such as anxiety and depression.

Chronically stressed individuals are reported to overconsume tasty, palatable foods like sucrose to blunt the psychological and physiological impacts of stress. Negative consequences of high-sugar intake on feeding behavior include increased metabolic disease burdens like obesity. However, the neural basis underlying long-term high-sugar intake-induced overeating during stress is not fully understood. To investigate this question, we used the two-bottle sucrose choice paradigm in mice exposed to chronic unpredictable mild stressors (CUMS) that mimic those of daily life stressors. After 21 days of CUMS paralleled by consecutive sucrose drinking, we explored anxiety-like behavior using the elevated plus maze and open field tests. The normal water-drinking stressed mice displayed more anxiety than the sucrose-drinking stressed mice. Although sucrose-drinking displayed anxiolytic effects, the sucrose-drinking mice exhibited binge eating (chow) and a compulsive eating phenotype. The sucrose-drinking mice also showed a significant body-weight gain compared to the water-drinking control mice during stress. We further found that c-Fos expression was significantly increased in the ventral part of the lateral septum (vLS) of the sucrose-treated stressed mice after compulsive eating. Pharmacogenetic activation of the vLS glutamate decarboxylase 2(GAD2) neurons maintained plain chow intake but induced a compulsive eating phenotype in the naïve GAD2-Cre mice when mice feeding was challenged by flash stimulus, mimicking the negative consequences of excessive sucrose drinking during chronic stress. Further, pharmacogenetic activation of the vLS^GAD2 neurons aggravated anxiety of the stressed GAD2-Cre mice but did not alter the basal anxiety level of the naïve ones. These findings indicate the GABAergic neurons within the vLS may be a potential intervention target for anxiety comorbid eating disorders during stress.

Post-stress cognitive impairment (PSCI) is defined as a persistent neuropsychiatric condition characterized by deficits in memory consolidation, executive functioning, and environmental interaction following exposure to violent stress. Despite its high incidence, PSCI remains underdiagnosed and lacks effective therapeutic strategies, posing a substantial societal burden and highlighting a critical gap in neuropsychiatric research. A major constraint in mechanistic studies is the persistent reliance on conventional paradigms, notably the Y-maze and novel object recognition test. Their limited sensitivity and poor translational relevance to human cognitive dysfunction, compounded by slow methodological innovation, significantly impede progress. Furthermore, the specific brain regions or neuronal populations contributing to PSCI pathogenesis are insufficiently explored. To address this, we assessed post-stress cognitive impairment in mice using a triple approach: Skinner box assays, traditional behavioral paradigms, and integrated 3D ethological analysis. This multi-method framework provides novel insights for refining animal models and advancing mechanistic understanding. Using c-Fos-based whole-brain screening, we identified the dentate gyrus (DG) as a key region involved in PSCI. Stress caused by violence markedly increased activity in DG CaMKII-expressing neurons. Chemogenetic inhibition of these neurons effectively alleviated stress-induced mild cognitive impairment phenotypes. In summary, by applying novel behavioral assessment tools, this study demonstrates that DG CaMKII neurons play a critical role in regulating post-stress cognitive impairment.