Accumulated evidence indicates that sympathetic nerves may potentiate tumor growth, including melanoma. To elucidate possible mechanisms for this effect, we performed chemical sympathectomy by intraperitoneal (i.p.) injection of the neurotoxin 6-hydroxydopamine hydrobromide (100 mg/kg of body weight); in nine adult male C57BL/6J mice; nine control mice received i.p. vehicle (VEH). Seven days later, all mice were injected subcutaneously with 3 × 10(3) B16-F10 melanoma cells. Mice were euthanized 20 d after injection of melanoma cells, for measurement of tumor weight and expression of genes related to sympathetic signaling, apoptosis, hypoxia and angiogenesis in tumor tissue. To assess potential involvement of the hypothalamo-pituitary-adrenocortical axis in the effect of sympathectomy on melanoma growth, concentrations of plasma corticosterone and level of glucocorticoid receptor mRNA in tumor tissue were determined. We found that sympathectomy significantly attenuated melanoma growth (tumor weight 0.29 ± 0.16 g versus 1.02 ± 0.30 g in controls; p < 0.05). In tumor tissue from sympathectomized mice, we found significantly increased gene expression (measured by real-time PCR), relative to VEH-injected controls, of tyrosine hydroxylase, neuropeptide Y and glucocorticoid receptor (all p < 0.05), and alpha1, beta1 and beta3 adrenergic receptors (all p < 0.025), and factors related to apoptosis (Bcl-2 and caspase-3; p < 0.05) and hypoxia (hypoxia inducible factor 1 alpha) (p = 0.005). Plasma corticosterone concentrations were significantly elevated (p < 0.05) in these mice. Our findings indicate that sympathectomy induces complex changes in the tumor microenvironment reducing melanoma growth. Such complex changes should be considered in the prediction of responses of cancer patients to interventions affecting sympathetic signaling in tumor tissue and its environment.

Modern society is characterized by the ubiquity of stressors that affect every individual to different extents. Furthermore, experimental, clinical, and epidemiological data have shown that chronic activation of the stress response may participate in the development of various somatic as well as neuropsychiatric diseases. Surprisingly, the role that stress plays in the etiopathogenesis of Alzheimer's disease (AD) has not yet been studied in detail and is therefore not well understood. However, accumulated data have shown that neuroendocrine and behavioral changes accompanying the stress response affect neuronal homeostasis and compromise several key neuronal processes. Mediators of the neuroendocrine stress response, if elevated repeatedly or chronically, exert direct detrimental effects on the brain by impairing neuronal metabolism, plasticity, and survival. Stress-induced hormonal and behavioral reactions may also participate in the development of hypertension, atherosclerosis, insulin resistance, and other peripheral disturbances that may indirectly induce neuropathological processes participating in the development and progression of AD. Importantly, stress-induced detrimental effects as etiological factors of AD are attractive because they can be reduced by several approaches including behavioral and pharmacological interventions. These interventions may therefore represent an important strategy for prevention or attenuation of the progression of AD.

Objectives.Previously we have shown that 20 days aft er the tumor cells injection smaller melanomas have been developed in chemically sympathectomized mice in comparison with animals having intact sympathetic nervous system. However, it is known that chemical sympathectomy reduces the sympathetic neurotransmission only temporarily. In the present study, we monitored the survival of the sympathectomized mice with melanoma with an attempt to fi nd out how long the suppressing eff ect of sympathectomy on the melanoma growth may endure.Methods. Th e chemical sympathectomy was performed by intraperitoneal injection of neurotoxin 6-hydroxydopamine in male C57BL/6J mice. Seven days later, the animals were injected subcutaneously with B16-F10 melanoma cells. Th en, melanoma development, survival of the tumorbearing mice and weight of the developed tumor mass were analyzed.Results. Sympathectomy delayed the development of the palpable tumors (18th day vs.14th day) and signifi cantly prolonged the survival of the tumor-bearing mice (median 34 days vs. 29 days). However, the weight of the developed melanoma was signifi cantly increased in the sympathectomized mice in comparison with the animals having intact sympathetic nervous system.Conclusions. Th e data of the present study showed that eff ect of the chemical sympathectomy, performed before the tumor growth induction, persisted even at the time when sympathetic nerves started to regenerate that resulted in a prolonged survival of the mice with melanoma. However, comparing to our previous study, in which we have shown a reduced tumor mass in earlier stages of the tumor growth, specifi cally 20 days aft er melanoma cells injection, now we indicate that in later stages of the melanoma progression, the tumor mass was signifi cantly increased in sympathectomized animals. Th ese contra-intuitive fi ndings may indicate that interventions aff ecting the sympathetic nervous system may exert complex eff ect on the tumor progression. Based on these data we may suggest that the potential therapeutic interventions aff ecting the sympathetic signaling in the tumor tissue and its microenvironment should attenuate the sympathetic neurotransmission not only temporarily but till the complete regression of the tumor tissue.