PervaizN, Hoffman-Goetz L. Immune cell inflammatory cytokine responses differ between central and systemic compartments in response to acute exercise in mice. 2012;18:142-57.  


Exhaustive exercise induces apoptosis and oxidative stress in systemic organs and tissues and is associated with increased levels of pro-inflammatory cytokines. The effects of acute exercise on cytokine expression and apoptosis of immune cells in the central nervous
system (CNS) have not been well characterized.


We investigated the effects of a single bout of strenuous exercise on the expression of TNF-alpha, IL-6, and IL-beta, as well as the apoptotic status of cells in the hippocampus of healthy mice. To compare central vs. systemic differences, cytokine expression in the intestinal lymphocytes of a subset of mice were also assessed.


Female C57BL/6 mice were divided into three groups: sedentary controls (NOTREAD) (n = 22), treadmill exercise with immediate sacrifice (TREAD-Imm) (n = 21), or treadmill exercise with sacrifice after 2 hours (TREAD-2h). TNF-alpha, IL-6, and IL-1beta expression in the hippocampus and intestinal lymphocytes were measured by Western blot analysis. Percentages of hippocampal cells undergoing apoptosis (Annexin+) or necrosis (Propidium Iodide+) were determined through flow cytometry. Plasma levels of 8-isoprostane and corticosterone were measured using commercially available EIA kits.


Acute treadmill exercise led to significant decreases in TNF-alpha (p<0.05) and increases in IL-6 (p<0.05) expression in the hippocampus of healthy mice. No effects of acute exercise on the apoptotic status of hippocampal cells were observed. In intestinal lymphocytes, the exercise bout led to significant increases in TNF-alpha (p<0.05), IL-6 (p<0.05), and IL-1beta (p<0.05). Acute exercise was associated with a significant increase in both plasma 8-isoprostane (p<0.05) and corticosterone (p<0.05) levels.


Acute exercise differentially affects the pattern ofpro-inflammatory cytokine expression in the hippocampus compared to intestinal lymphocytes and, further, does not induce apoptosis in hippocampal cells


Arevalo MA, Santos-Galindo M, Acaz-Fonseca E, Azcoitia I, Garcia-Segura LM. Gonadal hormones and the control of reactive gliosis. 2012 Feb 28.

Astrocytes and microglia respond to central nervous system (CNS) injury with changes in morphology, proliferation, migration and expression of inflammatory regulators. This phenomenon is known as reactive gliosis. Activation of astrocytes and microglia after acute neural insults, such as stroke or traumatic CNS injury, is considered to be an adaptive response that contributes to minimize neuronal damage. However, reactive gliosis may amplify CNS damage under chronic neurodegenerative conditions. Progesterone, estradiol and testosterone have been shown to control reactive gliosis in different models of CNS injury, modifying the number of reactive astrocytes and reactive microglia and the expression of anti-inflammatory and proinflammatory mediators. The actions of gonadal hormones on reactive gliosis involve different mechanisms, including the modulation of the activity of steroid receptors, such as estrogen receptors α and β, the regulation of nuclear factor-κB mediated transcription of inflammatory molecules and the recruitment of the transcriptional corepressor c-terminal binding protein to proinflammatory promoters. In addition, the Parkinson's disease related gene parkin and the endocannabinoid system also participate in the regulation of reactive gliosis by estradiol. The control exerted by gonadal hormones on reactive gliosis may affect the response of neural tissue to trauma and neurodegeneration and may contribute to sex differences in the manifestation of neurodegenerative diseases. However, the precise functional consequences of the regulation of reactive gliosis by gonadal hormones under acute and chronic neurodegenerative conditions are still not fully clarified


Johnson RT, Schneider A, DonCarlos LL, Breedlove SM, Jordan CL. Astrocytes in the rat medial amygdala are responsive to adult androgens. 2012 Aug 1;520(11):2531-44. doi: 10.1002/cne.23061.

The posterodorsal medial amygdala (MePD) exhibits numerous sex differences including differences in volume and in the number and morphology of neurons and astroctyes. In adulthood, gonadal hormones, including both androgens and estrogens, have been shown to play a role in maintaining the masculine character of many of these sex differences, but whether adult gonadal hormones maintain the increased number and complexity of astrocytes in the male MePD was unknown. To answer this question we examined astrocytes in the MePD of male and female Long Evans rats that were gonadectomized as adults and treated for 30 days with either testosterone or a control treatment. At the end of treatment brains were collected and immunostained for glial fibrillary acidic protein. Stereological analysis revealed that adult androgen levels influenced the number and complexity of astrocytes in the MePD of both sexes, but the specific effects of androgens were different in males and females. However, sex differences in the number and complexity of adult astrocytes persisted even in the absence of gonadal hormones in adulthood, suggesting that androgens also act earlier in life to determine these adult sex differences. Using immunofluorescence and confocal microscopy, we found robust androgen receptor immunostaining in a subpopulation of MePD astrocytes, suggesting that testosterone may act directly on MePD astrocytes to influence
their structure and function.