Behaviour and cognitive changes correlated with hippocampal neuroinflammaging and neuronal markers in female SAMP8, a model of accelerated senescence.
Senescence accelerated mice P8 (SAMP8) is a phenotypic model of age, characterized by deficits in memory and altered behaviour. Here, we determined the effect of age in SAMP8, and compared with the resistant strain, SAMR1, in behaviour and learning parameters linking these disturbances with oxidative stress environment. We found impairment in emotional behaviour with regard to fear and anxiety in young SAMP8 vs. age-mated SAMR1. Differences were attenuated with age. In contrast, learning capabilities are worse in SAMP8, both in young and aged animals, with regard to SAMR1. These waves in behaviour and cognition were correlated with an excess of oxidative stress (OS) in SAMP8 at younger ages that diminished with age. In this manner, we found changes in the hippocampal expression of ALDH2, IL-6, HMOX1, COX2, CXCL10, iNOS, and MCP-1 with an altered amyloidogenic pathway by increasing the Amyloid beta precursor protein (APP) and BACE1, and reduced ADAM10 expression; in addition, astrogliosis and neuronal markers decreased. Moreover, Superoxide dismutase 1 (SOD1) and Nuclear factor-kappa beta (NF-kβ) expression and protein levels were higher in younger SAMP8 than in SAMR1. In conclusion, the accelerated senescence process present in SAMP8 can be linked with an initial deregulation in redox homeostasis, named neuroinflammaging, by inducing molecular changes that lead to neuroinflammation and the neurodegenerative process. These changes are reflected in the emotional and cognitive behaviour of SAMP8 that differs from that of SAMR1 and that highlighted the importance of earlier oxidative processes in the onset of neurodegeneration.
Department of Pharmacology and Therapeutic Chemistry, Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, Spain.
Christian
C
Griñan-Ferré
Department of Pharmacology and Therapeutic Chemistry, Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, Spain.
Verónica
V
Palomera-Ávalos
Department of Pharmacology and Therapeutic Chemistry, Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, Spain.
Dolors
D
Puigoriol-Illamola
Department of Pharmacology and Therapeutic Chemistry, Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, Spain.
Antoni
A
Camins
Department of Pharmacology and Therapeutic Chemistry, Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, Spain.
David
D
Porquet
Department of Cellular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Avda. Diagonal 646, 08028 Barcelona, Spain.
Virginia
V
Plá
Department of Cellular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Avda. Diagonal 646, 08028 Barcelona, Spain.
Fernando
F
Aguado
Department of Pharmacology and Therapeutic Chemistry, Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, Spain. Electronic address: pallas@ub.edu.
Mercè
M
Pallàs
D000375:Aging / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D003071:Cognition; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008568:Memory; D051379:Mice; D023421:Models, Animal; D018384:Oxidative Stress / Q000235:genetics*
D015415:Biomarkers
Ageing; Behaviour; Cognition; Inflammation; Learning; Neurodegeneration; Oxidative stress