Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB256

Poster Communications

Spray-dried animal plasma supplementation attenuates aging neuroinflammation in SAMP8 mice

M. Moretó1, L. Miró1,2, A. Garcia-Just1, C. Rosell-Cardona1, C. Amat1, J. Polo2, C. Griñán-Ferré3, M. Pallàs3, A. Pérez-Bosque1

1. Biochemistry and Physiology, Universitat de Barcelona, Barcelona, Spain. 2. Research, APC Europe SLU, Granollers, Spain. 3. Pharmacology, Toxicology and Therapeutic Chemistry, Universitat de Barcelona, Barcelona, Spain.

Dietary supplementation with spray-dried animal plasma (SDP) has anti-inflammatory effects in several models of inflammation. In SAMP8 mice, a strain prone to senescence, SDP reduces brain neuroinflammation and oxidative stress and prevents the aging effects on short- and long-term memory (Miró et al, 2018). We have now studied if SDP can also improve neuronal integrity in senescent mice by reducing astrogliosis and microgliosis, both involved in the development of cognitive pathologies. Experiments were performed on male mice of the SAMP8 strain. The groups were: 2 months-old (young, 2M; 25 g, n=12) and 6 months-old (senescent) mice (32-34 g) fed either a Control diet (6M-CTL; n=12) or a diet containing 8% SDP (6M-SDP; n=12) for 4 months. Both diets were isoenergetic and isonitrogenous. Mice were anaesthetized by an i.p. injection of ketamine/xylazine (100/10 mg/kg). Brain tissue was perfused with 4% paraformaldehyde and stored at -80°C. Histological studies were carried out on 20 μm sections. Markers of astrogliosis (GFAP) and microgliosis (IBA and CD11b) were quantified by immunostaining. Digital fluorescence images were acquired by a SPII confocal scanning laser microscope. The abundance of presynaptic marker synaptophysin (SYN), postsynaptic marker PSD95, and p-NF-kB were determined by Western blot. Endothelial adhesion molecules (Vcam-1 and Icam-1) and Tnf-α expression were quantified by Real Time-PCR. Data were analyzed by one-way ANOVA. Senescence increased the expression (fold change) of neuroinflammation markers such as Tnf-α (2M: 1.0±0.3; 6M-CTL: 5.3±0.8, p=0.002, n=6) and p-NF-kB (2M: 1.0±0.1; 6M-CTL: 1.6±0.3, p=0.057, n=5) and adhesion molecules Vcam-1 (2M: 1.0±0.2; 6M-CTL: 3.3±0.7) and Icam-1 (2M: 1.0±0.2; 6M-CTL: 4.2±1.0), both p=0.015, n=5. The SDP-supplemented diet prevented in part neuroinflammation since the value of Tnf-α was 2.7±0.8 (p=0.026) and that of p-NF-kB of 0.9±0.1 (p=0.018). Aging decreased the abundance of SYN, from 1.0±0.1 (2M) to 0.7±0.1 (6M-CTL; p=0.037), indicating neural loss and this effect was prevented by SDP (1.1±0.1, p=0.012, n=6). Senescence increased the percentage of GFAP+ cells from 11.4±0.8% (2M) to 18±1.5% (6M-CTL, p=0.008 n=4), IBA1+ cells, from 3.7±0.3% (2M) to 4.9±0.3% (6M-CTL, p=0.033, n=4), and the mean fluorescence intensity of CD11b cells augmented 32% in senescent mice (2M: 99.1; 6M-CTL: 131.7±6.1, p=0.017, n=4). These effects of aging were also prevented by SDP (GFAP+, 11.3±1.5%, p=0.007; IBA+ cells, 3.6±0.3%, p=0.028; CD11b, 93.7±8.4, p=0.011). These results suggest that oral SDP supplementation can maintain neuronal integrity by reducing aging-associated neuroinflammation, astrogliosis and microgliosis.

Where applicable, experiments conform with Society ethical requirements