4-Hydroxynonenal, a product of oxidative stress, leads to an antioxidant response in optic nerve head astrocytes.

Oxidative stress has been implicated in the pathogenesis of several neurodegenerative disorders including primary open-angle glaucoma (POAG) an optic neuropathy characterized by loss of retinal ganglion cell (RGC) axons and remodeling of the optic nerve head (ONH). Previous findings in glaucomatous astrocytes suggested increased oxidative stress and lipid peroxidation in human optic nerves. We studied the dose and time dependent effects of 4-hydroxynonenal (HNE), a by-product of lipid peroxidation, on the viability of primary cultures of human ONH astrocyte. A significant depletion of glutathione (GSH) level was observed in normal astrocytes after exposure to HNE for 1 h and 3 h. Untreated glaucomatous astrocytes exhibited depleted levels of GSH which increased slightly after exposure to HNE. Both normal and glaucomatous astrocytes recovered GSH levels after 24 h of removal of HNE. HNE caused significant increases in expression of antioxidant enzymes, glutamate cysteine ligase catalytic subunit (GCLC), aldo-keto reductase 1C family member 1 (AKR1C1) and glutathione S-transferase-alpha4 (GSTA4). HNE induced expression of the transcription factor Nrf2, which coordinates the upregulation of detoxification enzymes. In addition, ONH astrocytes responded to HNE by activation and transcription of cFOS and NFkB, which regulate physiological protective responses against oxidative stress. Our results indicate that ONH astrocytes exhibit a strong antioxidant response to HNE treatment by inducing the transcription factors cFOS, NFkB, and Nrf2, which upregulate the expression of GCLC, to produce more GSH in the cell. AKR1C1 was also upregulated after HNE treatment to inactivate HNE, independent of GSH availability in the cells. Collectively these data indicate that ONH astrocytes can efficiently counteract the neurotoxic effects of HNE offering protection in the optic nerve by releasing GSH and antioxidant enzymes to eliminate the products of chronic oxidative stress.

An evaluation of an intergenerational consultation process to increase personal authority in the family system.

This paper reports an evaluation of an intergenerational consultation process designed to help people change significant relationships in the three-generational family system. The paper first describes the theory behind the consultation process that focuses on increasing personal authority in the family system; this is followed by a description of the consultation process. Clients who participated in the consultation process were compared to clients who participated in systems-oriented psychotherapy. The results indicate that clients who participated in the intergenerational consultation reported significantly more change in intergenerational triangulation and personal authority than did the control group. There were no differences between the groups in reported change in presenting problems, satisfaction with therapy, or helpfulness of therapy. Persons who had their parents in the office for a consultation also reported significantly more change in personal authority and less intergenerational intimidation than did clients who did not have their parents in the office for consultation. Implications of these findings for intergenerational theory and therapy as well as future research are discussed.