Organizational changes in cholinergic activity and enhanced visuospatial memory as a function of choline administered prenatally or postnatally or both.

Abstract

This experiment was an examination of the effects of supplemental dietary choline chloride given prenatally (to the diet of pregnant rats) and postnatally (intubed directly into the stomachs of rat pups) on memory function and neurochemical measures of brain cholinergic activity of male albino rats when they became adults. The data demonstrate that perinatal choline supplementation causes (a) long-term facilitative effects on working and reference memory components of a 12-arm radial maze task, and (b) alternations of muscarinic receptor density as indexed by [3H]quinuclidinyl benzilate (QNB) binding and choline acetyltransferase (ChAT) levels in the hippocampus and frontal cortex of adult rats. An analysis of the relationship between these organizational changes in brain and memory function indicated that the ChAT-to-QNB ratio in the hippocampus is highly correlated with working memory errors, and this ratio in the frontal cortex is highly correlated with reference memory errors.

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

“…For example, in the liver, CpGs at positions 8 and 15 were highly methylated (30 -60%), whereas the 19th CpG was poorly methylated (4 -8%). There was also a tendency for higher methylation in the core of DMR2 (positions [5][6][7][8][9][10][11][12]. Surprisingly, but in agreement with the results on global DNA methylation reported above, choline deficiency was associated with the highest degree of methylation in the liver at E17 (p Ͻ 0.00001, ANOVA).…”

“…Studies in animal models (2)(3)(4)(5) as well as recent epidemiological investigations in humans (6) indicate that choline intake during gestation is particularly important for the normal development and function of the central nervous system. In a frequently used experimental model that employs offspring of pregnant rats or mice consuming diets of varying choline content during the 7-day period of the second half of gestation (embryonic days E11-17), prenatal choline deficiency causes deficits in certain memory tasks (7), whereas prenatal choline supplementation leads to enhanced memory and attention and prevents agerelated memory decline (7)(8)(9)(10)(11)(12)(13). These behavioral changes are accompanied by electrophysiological, neuroanatomical, and neurochemical alterations that persist in the adulthood and old age (2)(3)(4)(5) and, remarkably, by altered patterns of brain gene expression postnatally (14).…”

Prenatal choline supplementation increases sensitivity to time by reducing non-scalar sources of variance in adult temporal processing

“…There is a variety of behavioral and neurobiological evidence supporting the view that rats given prenatal-choline supplementation express increased memory capacity and are capable of forming more enduring memories in adulthood (Loy et al, 1991;Meck et al, 1988Meck et al, , 1989Mellott et al, 2004;Montoya et al, 2000;Williams et al, 1998). For example, recent studies have shown that prenatal-choline supplementation can elevate the baseline level of hippocampal neurogenesis in adult rats, a phenomenon that is considered to be facilitative of certain types of memory (e.g., Glenn, et al, 2007).…”

Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus

“…Prenatal and early postnatal choline supplementation has also been shown to protect against impairments in performance on hippocampal-dependent tasks caused by aging (Meck et al, 1988(Meck et al, , 1989Meck & Williams, 2003;McCann et al, 2006) or neonatal alcohol exposure (Thomas et al, 2004(Thomas et al, , 2007Wagner & Hunt, 2006). While the mechanism by which prenatal choline supplementation confers neuroprotection is not fully understood, choline is a vital nutrient important for several biological functions: acetylcholine synthesis, building biological membranes, cell signaling, and methyl donation (Blusztajn, 1998;Zeisel, 2004Zeisel, , 2006.…”

“…All dams were individually housed in clear polycarbonate cages (27.9×27.9×17.8 cm) that were individually ventilated, and the colony was maintained at 21°C on a 12-h light/dark cycle with lights on at 7 a.m. Dams were fed a control diet ad libitum (AIN76-A from Dyets, American Institute of Nutrition, ICN, Nutritional Biochemical, Cleveland, Ohio; 1.1 g/kg choline chloride substituted for choline bitartrate). Prenatal diet treatments were the same as those used in studies showing memory enhancing and memory protecting effects of prenatal choline supplementation (Meck et al, 1988(Meck et al, , 1989Yang et al, 2000;Holmes et al, 2002;Meck & Williams, 2003). On the morning of ED11 to the morning of ED18 , pregnant dams were either given ad libitum access to a control diet (n = 14) or a choline supplemented diet (n = 6).…”