Abstract
The integrity of neuroprotection is an important component against the development of cognitive disorders and AD. Within this context, DHEAS would seem to have some positive metabolic and endocrine effects to delay brain aging by recovering the impairment of neuroprotective growth factors. In the present study we measured by ELISA the secretion of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGFβ1) in the supernatants of cultured circulating peripheral blood mononuclear cells (PBMC) from which natural killer cells (NK) were separated (PBMC-NK) (pg/ml/7.75 × 10 6 cells) in healthy subjects and in age-matched patients with mild to moderate AD. The growth factors were measured in spontaneous conditions and after stimulation with growth hormone (GH) 1 μg/ml (IGF-1), lipopolysaccharide (LPS) 1 μg/ml (VEGF) and glucose 10 μM (TGF(β1). AD group demonstrated at baseline a severe reduction of IGF-1 (3.7 + 1.2 pg/ml after GH), VEGF (63 ± 18 pg/ml spontaneous and 210 ± 65 pg/ml after LPS) and TGF(β1 (33 ± 10 pg/ml spontaneous and 75 ± 12 pg/ml after glucose) secretions compared to healthy elderly subjects (IGF-1, 9.5 ± 2.8 pg/ml after GH, p < 0.001; VEGF, 117 ± 38 pg/ml spontaneous, p < 0.001 and 690 ± 120 pg/ml after LPS, p < 0.001; and TGF(β1, 73 ± 21 pg/ml spontaneous, p < 0.001 and 169 ± 53 pg/ml after glucose, p < 0.001). Significant positive correlations between IGF-1 and VEGF concentrations were found both in healthy subjects (r = 0.87, p < 0.001) and in AD subjects (r = 0.87, p < 0.001). The co-incubation of NK cells with DHEAS (10 6 M/ml/cells) significantly increase IGF-1, VEGF and TGF (β1 production, reaching in AD group the normal concentrations found in healthy subjects (IGF-1, 7.9 + 2.4 pg/ml after GH; VEGF, 105 ± 31 pg/ml spontaneous and 670 ± 112 pg/ml after LPS; and TGFfβ1, 68 ± 18 pg/ml spontaneous and 155 ± 48 pg/ml after glucose). These data suggested that DHEAS is able to increase the immunoendocrine production of neuroprotective growth factors, which is reduced in AD subjects, so suggesting a new approach in the treatment of dementia.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
