Are the neuroprotective effects of estradiol and physical exercise comparable during ageing in female rats?
Ageing of the brain is accompanied by variable degrees of cognitive decline. Estrogens have profound effects on brain ageing by exerting neurotrophic and neuroprotective types of action. Furthermore, exercise has also been claimed to play a role in the non-pharmacological prevention of psycho-neuronal decline with ageing. In the present study the question was asked whether chronic physical exercise might substitute the action of estrogens in aged rats. We compared the effects of 17β-estradiol (E2) treatment and long-term moderate physical exercise in ageing (15 months, early stage of ageing) and old (27 months) female rats, on cognitive functions and the relevant intracellular molecular signaling pathways in the hippocampus. Results showed that both treatments improved attention and memory functions of the 15 months old rats. Like E2, physical training enhanced the level of brain derived nerve growth factor and the activation of PKA/Akt/CREB and MAPK/CREB pathways. The treatments also enhanced the levels of synaptic molecules synaptophysin and synapsin I, which could explain the improved cognitive functions. In the 27 months old rats the behavioral and molecular effects of E2 were indistinguishable from those found in the 15 months old animals but the effects of physical exercise in most of the measures proved to be practically ineffective. It is concluded that the effectiveness of regular and moderate intensity physical exercise is age-dependent while the action of E2 treatment is comparable between the ageing and old female rats on maintaining cognition and its underlying molecular mechanisms.
KeywordsEstradiol Exercise Ageing Cognition Hippocampus
- Bohacek J, Daniel JM (2009) The ability of oestradiol administration to regulate protein levels of oestrogen receptor alpha in the hippocampus and prefrontal cortex of middle-aged rats is altered following long- term ovarian hormone deprivation. J Neuroendocrinol 21(7):640–647PubMedCrossRefGoogle Scholar
- Bradford MM, Williams WL (1976) New, rapid, sensitive method for protein determination. Fed Proc 35(3):274Google Scholar
- Kawas C (1998) A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: The Baltimore Longitudinal Study of Aging (vol 48, pg 1517, 1997). Neurology 51(2):654Google Scholar
- Koltai E, Zhao Z, Lacza Z, Cselenyak A, Vacz G, Nyakas C, Boldogh I, Ichinoseki-Sekine N, Radak Z (2011) Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage. Rejuvenation Res 14(6):585–596PubMedCrossRefGoogle Scholar
- McEwen BS, Coirini H, Schumacher M (1990) Steroid effects on neuronal-activity––when is the genome involved. In: Chadwick D, Widdows K (eds) Steroids and neuronal activity, vol 153. Ciba Foundation Symposia, pp 3–21Google Scholar
- Meyer TE, Waeber G, Lin J, Beckmann W, Habener JF (1993) The promoter of the gene encoding 3′,5′-cyclic adenosine-monophosphate (CAMP) response element binding-protein contains CAMP response elements––evidence for positive autoregulation of gene-transcription. Endocrinology 132(2):770–780PubMedCrossRefGoogle Scholar
- Nyakas C, Felszeghy K, Szabó R, Keijser JN, Luiten PGM, Szombathelyi Z, Tihanyi K (2009) Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on nmda-induced neurotoxicity in a rat entorhinal cortex lesion model. CNS Neurosci Ther 15(2):89–99PubMedCrossRefGoogle Scholar
- Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TVP, Bramham CR (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. J Neurosci 22(5):1532–1540PubMedGoogle Scholar