Dietary choline supplementation increases the density of nicotine binding sites in rat brain
ABSTRACT The objective of these studies was to determine whether the chronic administration of choline, like the chronic administration of nicotine, increased the density of nicotine binding sites in brain. To accomplish this, rats were maintained on a choline-deficient (0% choline chloride), basal choline (0.2% choline chloride) or choline-supplemented (2.0% choline chloride) diet for 30 days or were fed a standard rodent chow and received injections of saline or nicotine (3.6 mumol/kg s.c.) twice daily for 10 days. Membranes from striatum, hippocampus and frontal cortex were isolated, and the binding of L-(-)-[N-methyl-3H]nicotine (0.5-60 nM) was studied. A single binding site for nicotine was evident for all brain regions from all animals studied with a dissociation constant (Kd) of approximately 2 to 5 nM. Chronic supplementation with choline, which increased circulating choline levels by 92%, did not alter binding affinity, but increased significantly the maximal number (Bmax) of nicotine binding sites in cortical and hippocampal membranes by 20 and 73%, respectively, compared to animals fed the basal choline diet; the Bmax in striatal membranes was unaltered. Nicotine binding parameters for membranes from animals maintained on the choline-deficient diet were not different from those maintained on the basal diet. The chronic administration of nicotine did not alter binding affinity, but increased significantly the maximal density of nicotine binding sites in striatal and cortical preparations by 47 and 18%, respectively; the Bmax in hippocampal membranes was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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- "Animals were randomly assigned into two dietary exposure groups: standard choline diet (containing 0.2% choline-TD 03118; Harlan Teklad, Madison, WI) and a choline-supplemented diet (2% choline- TD 03119). These studies employed a concentration of 2% choline for dietary supplementation because previous studies have shown that this is a palatable diet that results in significant increases in the number of CNS ␣7 nAChRs (Coutcher et al., 1992; Guseva et al., 2006). Diets were nutritionally matched with respect to all ingredients except choline. "
ABSTRACT: Novel pharmacological approaches that safely and effectively lessen the degree of neurological impairment following traumatic brain injury (TBI) are sorely needed. Non-invasive approaches that could be used over an extended periods of time might be particularly useful. Previous studies from our lab have hypothesized that TBI-induced decreases in hippocampal and cortical alpha7 neuronal nicotinic cholinergic receptor (nAChR) expression might contribute to cognitive impairment that follows brain injury. The purpose of this study was to determine whether the low-potency, but selective alpha7 nAChR agonist choline might be a useful treatment for improvement of neurological outcome in a rat model of TBI. Male Sprague-Dawley rats were exposed to control or choline-supplemented diets for 2 weeks prior to experimental brain injury (1.5-mm cortical contusion injury) and throughout the recovery phase. Dietary choline supplementation resulted in a modest degree of improvement in spatial memory as assessed in the Morris water maze test. In addition, choline treatment resulted in significant cortical tissue sparing, reduced brain inflammation, and normalized some TBI-induced deficits in nAChR expression. The results of this study suggest that alpha7 nAChR agonists may be useful drugs to enhance recovery following brain injury.Journal of Neurotrauma 09/2008; 25(8):975-83. DOI:10.1089/neu.2008.0516 · 3.97 Impact Factor
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- "Choline is an essential nutrient that is critical for brain development and function (Zeisel, 2006a). A growing literature illustrates that pre-and/or early postnatal choline supplementation in otherwise typically developing rats leads to long-lasting morphological (Li et al., 2004; Loy et al., 1991; Williams et al., 1998), electrophysiological (Jones et al., 1999; Pyapali et al., 1998), and neurochemical (Blusztajn et al., 1998; Cermak et al., 1999; Cermak et al., 1998; Coutcher et al., 1992; Meck et al., 1989; Montoya et al., 2000) changes in the CNS that contribute to longlasting cognitive enhancements (McCann et al., 2006; Meck and Williams, 1997; Meck et al., 1988; Meck and Williams, 2003). Perinatal choline supplementation can also enhance cognitive improvements to later environmental manipulations, such as enriched environment (Tees, 1999). "
ABSTRACT: Despite the harmful effects of fetal alcohol exposure, some pregnant women continue to drink alcohol. Thus, it is imperative to pursue safe, effective treatments for children with fetal alcohol spectrum disorders. Using an animal model, our laboratory has demonstrated that choline, an essential nutrient, effectively reduces the severity of some fetal alcohol effects, even when administered after the ethanol insult is complete. The present study investigated whether there is a critical developmental period when choline is most effective in attenuating ethanol's teratogenic effects. Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol during the third trimester equivalent brain growth spurt (postnatal days (PD) 4-9) via intubation. A non-intubation control group and a sham intubation control group were included. Following ethanol exposure, pups received subcutaneous injections of saline vehicle or choline chloride (100 mg/kg/day) from PD 11-20, PD 21-30, or PD 11-30. Beginning on PD 45, subjects were tested on a Morris water maze spatial learning task. Performance of both the ethanol-exposed group that did not receive choline and the ethanol-exposed group treated with choline from PD 21-30 was significantly impaired compared to controls during acquisition of the Morris water maze task. Performance of ethanol-exposed groups treated with choline from PD 11-20 or PD 11-30 was intermediate, not differing significantly from any other groups. However, during the probe trial, ethanol exposure produced significant deficits in spatial memory which were mitigated by all choline treatments, regardless of the timing of administration. These findings suggest that choline's therapeutic window may be very large, or spans across the two developmental periods examined in this study. Importantly, these findings indicate that choline supplementation may effectively reduce some alcohol-related learning impairments, even when administered in later childhood.Brain Research 09/2008; 1237:91-100. DOI:10.1016/j.brainres.2008.08.048 · 2.83 Impact Factor
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- "In contrast, perinatal choline supplementation can stimulate cell division in the embryonic brain  and can lead to long-lasting anatomical, electrophysiological, neurochemical, and behavioral alterations . Most notably, perinatal choline loading can lead to long-lasting enhancements in cholinergic functioning       and cognitive abilities      . "
ABSTRACT: Prenatal alcohol exposure can disrupt brain development, leading to a variety of behavioral alterations including learning deficits, hyperactivity, and motor dysfunction. We have been investigating the possibility that perinatal choline supplementation may effectively reduce the severity of alcohol's adverse effects on behavioral development. We previously reported that perinatal choline supplementation can ameliorate alcohol-induced learning deficits and hyperactivity in rats exposed to alcohol during development. The present study examined whether perinatal choline supplementation could also reduce the severity of motor deficits induced by alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4 to 9 via an artificial rearing procedure. Artificially and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4 to 30, whereas the other half received saline vehicle injections. On PD 35-37, subjects were tested on a parallel bar motor task, which requires both balance and fine motor coordination. Ethanol-exposed subjects exhibited significant motor impairments compared to both control groups whose performance did not differ significantly from one another. Perinatal choline treatment did not affect motor performance in either ethanol or control subjects. These data indicate that the beneficial effects of perinatal choline supplementation in ethanol-treated subjects are task specific and suggest that choline is more effective in mitigating cognitive deficits compared to motor deficits associated with developmental alcohol exposure.Neurotoxicology and Teratology 03/2004; 26(2):223-9. DOI:10.1016/j.ntt.2003.10.005 · 3.22 Impact Factor