Reversal of age-related learning deficiency by the vertebrate PACAP and IGF-1 in a novel invertebrate model of aging: the pond snail (Lymnaea stagnalis).
With the increase of life span, nonpathological age-related memory decline is affecting an increasing number of people. However, there is evidence that age-associated memory impairment only suspends, rather than irreversibly extinguishes, the intrinsic capacity of the aging nervous system for plasticity (1). Here, using a molluscan model system, we show that the age-related decline in memory performance can be reversed by administration of the pituitary adenylate cyclase activating polypeptide (PACAP). Our earlier findings showed that a homolog of the vertebrate PACAP38 and its receptors exist in the pond snail (Lymnaea stagnalis) brain (2), and it is both necessary and instructive for memory formation after reward conditioning in young animals (3). Here we show that exogenous PACAP38 boosts memory formation in aged Lymnaea, where endogenous PACAP38 levels are low in the brain. Treatment with insulin-like growth factor-1, which in vertebrates was shown to transactivate PACAP type I (PAC1) receptors (4) also boosts memory formation in aged pond snails. Due to the evolutionarily conserved nature of these polypeptides and their established role in memory and synaptic plasticity, there is a very high probability that they could also act as "memory rejuvenating" agents in humans.
Balaton Limnological Institute, Centre for Ecological Research, Hungarian Academy of Sciences, Tihany, Hungary. Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton. Department of Anatomy MTA-PTE, "Momentum" PACAP Team, University of Pécs, Hungary.
Zsolt
Z
Pirger
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton.
Souvik
S
Naskar
Balaton Limnological Institute, Centre for Ecological Research, Hungarian Academy of Sciences, Tihany, Hungary. Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton.
Zita
Z
László
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton.
György
G
Kemenes
Department of Anatomy MTA-PTE, "Momentum" PACAP Team, University of Pécs, Hungary.
Dóra
D
Reglődi
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton. I.Kemenes@sussex.ac.uk.
Ildikó
I
Kemenes
D000375:Aging / Q000187:drug effects / Q000502:physiology* / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects* / Q000502:physiology*; D008195:Lymnaea / Q000187:drug effects* / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D007334:Insulin-Like Growth Factor I
Learning; Memory.; PACAP