Anticancer Molecules in Brain

Clinical and epidemiological  studies have demonstrated that macroenvironmental factors are risk factors for the development and progression of tumor.  Macroenvironmental factors include a patient's physical, social environment and specific psychosocial factors such as chronic stress, depression, and lack of social support.

These observations raise intriguing questions on the brain-cancer connection. What are the molecules in brain linking environmental factors to cancer? Through which pathways do these brain molecule s modulate the peripheral cancer?  How do these molecules impact tumour growth and progression? The effects and mechanisms of the macroenvironment on systemic cancer are much less well defined, because most basic cancer research focuses on micro environmental factors of tumor.

To study environmental and psychosocial effects on cancer progression, our lab uses environmental enrichment (EE) as a eustress model. EE is a housing environment for laboratory animals, which, in contrast with the standard-environment (SE) cages used in most biomedical research, is socially, physically, and cognitively stimulating.EE has profound impacts on brain structure, function, and progression of neurologic diseases.

In Secondary Lymphoid Tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4+ T helper to CD8+ cytotoxic T lymphocytes. Then we identified hypothalamic BDNF as the brain molecule mediating EE’s effects on    cell immunity.  Hypothalamic overexpression of BDNF reproduced EE-induced T-cell phenotypes in SLT, whereas knock down of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Furthermore, this study explored the peripheral pathways BDNF employed to regulate T cell immunity. Both the β-blocker propranolol and the anti-corticosteroid compound mifepristone inhibited the EE-associated modulation of CD8+ T cells in SLT, suggesting that both the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis were involved.

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