Abstract
Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21–24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation, deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats.
Similar content being viewed by others
References
Aporti F, Borsato R, Calderini G, Rubini R, Toffano G, Zanotti A, Valzelli L, Goldstein L (1986) Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine. Neurobiol Aging 7:115–120
Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with aging and dementia. A quantitative study. Acta Neuropathol 37:111–118
Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 93:74–104
Biegon A, Greenberger V, Segal M (1986) Quantitative histochemistry of brain acetylcholinesterase and learning rate in the aged rat. Neurobiol Aging 7:215–217
Buzsaki G, Bickford RG, Armstrong DM, Ponomareff G, Chen KS, Ruiz R, Thal LS, Gage FH (1988) Electric activity in the neocortex of freely moving young and aged rats. Neuroscience 26:735–744
Calderini G, Aporti F, Bellini F, Bonetti AC, Rubini R, Teolato S, Xu C, Zanotti A, Toffano G (1985) Phospholipids as pharmacological tools in the aging brain. In: Horrocks LA, Kanfer JN, Porcellati G (eds) Phospholipid in the nervous system, vol 2, Physiological roles. Raven Press, New York, pp 11–19
Calderini G, Bonetti AC, Battistella A, Crews FT, Toffano G (1983) Biochemical changes of rat brain membranes with aging. Neurochem Res 8:483–491
Collier TJ, Bruemmer V, Sladek JR (1985) Aging of the locus coeruleus: behavioral correlates of norepinephrine (NE) deficiency in a subpopulation of aged F344 rats and the therapeutic influence of grafted NE neurons. Anat Rec 211:43A
Corwin J, Dean RL, III, Bartus RT, Rotrosen J, Watkins DL (1985) Behavioral effects of phosphatidylserine in the aged Fisher 344 rats: amelioration of passive avoidance deficits without changes in psychomotor task performance. Neurobiol Aging 6:11–15
Drago F, Canonico PL, Scapagnini U (1981) Behavioral effects of phosphatidylserine in aged rats. Neurobiol Aging 2:209–213
Gage FH, Björklund A (1986) Cholinergic septal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropine-sensitive mechanism. J Neurosci 6:2837–2847
Gage FH, Dunnett SB, Björklund A (1984a) Spatial learning and motor deficits in aged rats. Neurobiol Aging 5:43–48
Gage FH, Kelly PT, Björklung A (1984b) Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats. J Neurosci 4:2856–2865
Gallagher M, Pelleymounter MA (1988) An age-related spatial learning deficit: choline uptake distinguishes “impaired” and “unimpaired” rats. Neurobiol Aging 9:363–369
Geinisman Y, de Toledo-Morrell L, Morrell F (1986) Aged rats need a preserved complement of, perforated axospinous synapses per hippocampal neuron to maintain good spatial memory. Brain Res 398:266–275
Guidolin D, Milan F, Polato P, Nunzi MG, Toffano G (1989) Phosphatidylserine treatment prevents age-induced structural alterations in the rat septo-hippocampal system. In: Bazan N, Horrocks LA, Toffano G (eds) Phospholipid in the nervous system: biochemical and molecular pathology. Liviana Press Padova and Springer, Berlin Heidelberg New York Tokyo (in press)
Ingram DK, London, ED, Goodrick CL (1981) Age and neurochemical correlates of radial maze performance in rats. Neurobiol Aging 2:41–47
de Leon MJ, Harris SH, George AE, Reisberg B, Christman DR, Kricheff, II, Wolf AP (1983) Computed tomography and positron emission transaxial tomography evaluation of normal aging and Alzheimer's disease. J Cereb Blood Flow Metab 3:391–394
Leslie FM, Loughlin SE, Sternberg DB, McGaugh IL, Young LE, Zornetzer SF (1985) Noradrenergic changes and memory loss in aged mice. Brain Res 359:292–299
Lippa AS, Pelham RW, Beer B, Critchett, DJ, Dean RL, Bartus RT (1980) Brain cholinergic dysfunction and memory, in aged rats. Neurobiol Aging 1:13–19
Morris RGM (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60
Nilsson OG, Strecker RE, Daszuta A, Björklund A (1988) Combined cholinergic and serotoninergic denervation of the forebrain produces severe deficits in a spatial learning task in the rat. Brain Res 453:235–246
Nunzi MG, Milan F, Guidolin D, Toffano G (1987) Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration. Neurobiol Aging 8:501–510
Pedata F, Giovannelli L, Spignoli G, Giovannini MG, Pepen G (1985) Phosphatidylserine increases, acetylcholine release from cortical slices, in aged rats. Neurobiol Aging 6:337–339
Perry EK, Tomlinson BE, Blessed G, Bergman K, Gibson PH, Perry PH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2:1457–1459
Pradhan SN (1980) Minireview: central neurotransmitters and aging Life Sci 26:1643–1656
Rapp PR, Rosenberg RA, Gallagher M (1987) An evaluation of spatial information processing in aged rats. Behav Neurosci 101:3–12
Sherman KA, Kuster JE, Dean RL, Bartus RT, Friedman E (1981) Presynaptic cholinergic mechanisms in brain of aged rats with memory impairments. Neurobiol Aging 2:99–104
Strong R, Hicks P, Hsu L, Bartus RT, Enna SJ (1980) Age-related alterations in the rodent brain cholinergic system and behavior. Neurobiol Aging 1:59–63
Sun AY, Sun GY (1979) Neurochemical aspects of the membrane hypothesis of aging. Interdiscip Top Gerontol 15:34–53
Toffano G, Bruni, A (1980) Pharmacological properties of phospholipid liposomes. Pharmacol Res Commun 12:829–845
Vannucchi MG, Pepeu G (1987) Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aging rats. Neurobiol Aging 8:403–407
Wallace SE, Krauter EE, Campbell BA (1980) Animal models of declining memory in the aged. Short-term and spatial memory in aged rats. J Gerontol 35:355–363
Zornetzer SF, Thompson R, Rogers J (1982) Rapid forgetting in aged rats. Behav Neurol Biol 36:49–60
Author information
Authors and Affiliations
Additional information
We are grieved to record the unexpected, death of Professor L. Valzelli. He was a scientist of merit and a great humanitarian
Rights and permissions
About this article
Cite this article
Zanotti, A., Valzelli, L. & Toffano, G. Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology 99, 316–321 (1989). https://doi.org/10.1007/BF00445550
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00445550