Neuroprotective role of learning in dementia: a biological explanation.
Several epidemiological studies have found an association between low educational level (or low cognitively demanding occupations) and dementia. Although other studies have not found evidence to support such an association, there has been a general trend toward a "use it or lose it" concept which attempts to promote a neuroprotective role of intellectual activity against the development of dementia. Formation of amyloid-beta peptide (Abeta) in the brain plays a key role in the development of Alzheimer's disease whilst glutamate has been implicated in the pathophysiology of a number of neurological disorders including Alzheimer's disease and vascular dementia. Abeta can mediate neurodegeneration by a complex interaction of neurodegenerative processes that involve increasing extracellular concentration of glutamate, increasing intracellular Ca2+ concentration, and apoptosis. Long-term potentiation (LTP, a biological correlate of learning and memory) increases the sensitivity of hippocampal neurons to synaptically released glutamate whilst decreasing responses of neurons to bath applied glutamate receptor agonists and to hypoxia/ischemia in vitro. The effects of LTP are likely to involve changes in intracellular Ca2+ concentration. Based on these findings we are proposing that the LTP-induced neuroprotection in vitro may help explain the epidemiological evidence of a possible neuroprotective role of high intellectual activity against dementia.
Addae
Jonas I
JI
Department of Pre-Clinical Sciences, University of the West Indies, St Augustine Campus, Trinidad & Tobago. addae@carib-link.net
Youssef
Farid F
FF
Stone
Trevor W
TW
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003071:Cognition; D003704:Dementia / Q000503:physiopathology* / Q000517:prevention & control*; D016021:Epidemiologic Studies; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007858:Learning; D017774:Long-Term Potentiation / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D002118:Calcium