Seizure-induced memory impairment is reduced by choline supplementation before or after status epilepticus

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

“…These data are particularly important because prior work has shown a savings in hippocampal-dependent learning and memory at a similar time point following excitotoxin-induced SE in prenatally choline-supplemented rats (Yang et al, 2000;Holmes et al, 2002), suggesting that increased choline availability to the fetus may alter neural development such that the adult brain is protected from SE-induced damage and cognitive impairment. While these data do not rule out the possibility that choline supplements may have neuroprotective actions at other periods, we know that choline has profound memoryenhancing effects if it is supplemented on ED12-17 or PD15-30, but not at other developmental or adult timeframes (Meck & Williams, 2003).Consistent with previous findings (Holmes et al, 2002), we report that prenatally choline supplemented rats (SUP) showed reduced cell loss and gliosis in CA1, CA3, and hilus compared to control-fed rats even though all rats experienced the same severity and duration of seizure activity. While widespread neurodegeneration of the hippocampus is a notorious (Niquet et al, 1994a;Fujikawa et al, 2000;Kotloski et al, 2002), GABAergic neurons are particularly vulnerable (Obenaus et al, 1993;Houser & Esclapez, 1996;Esclapez & Houser, 1999;Shetty & Turner, 2001).…”

“…Given that prenatal choline supplementation has been shown to protect against seizure-induced memory loss on a hippocampal-dependent task (Yang et al, 2000;Holmes et al, 2002), we hypothesized that prenatal choline supplementation alters the neurophysiological response of the hippocampus to SE. To investigate this, we used a model of excitotoxic injury to examine whether prenatal choline availability modulates a variety of markers known to change shortly after SE, including hippocampal histopathology, glutamic acid decarboxylase (GAD) expression, dentate cell proliferation, neurogenesis, astrogliosis, and growth factor content.…”

“…Prenatal choline supplementation also enhances several features of adult hippocampal plasticity known to influence learning and memory function, such as increased baseline levels of neurogenesis, brain-derived neurotrophic factor (BDNF) (Glenn et al, 2007) and nerve growth factor (NGF) (Sandstrom et al, 2002); a reduced threshold to induce long-term potentiation (Pyapali et al, 1998;Jones et al, 1999); and enhanced depolarizationinduced mitogen-activated protein kinase (MAPK) and cAMP-response element binding protein (CREB) activation (Mellott et al, 2004). Enhanced hippocampal plasticity may underlie prenatal choline supplementation's neuroprotection of the hippocampus, rendering the hippocampus better able to withstand or recover from the deleterious effects of a neural insult.Given that prenatal choline supplementation has been shown to protect against seizure-induced memory loss on a hippocampal-dependent task (Yang et al, 2000;Holmes et al, 2002), we hypothesized that prenatal choline supplementation alters the neurophysiological response of the hippocampus to SE. To investigate this, we used a model of excitotoxic injury to examine whether prenatal choline availability modulates a variety of markers known to change shortly after SE, including hippocampal histopathology, glutamic acid decarboxylase (GAD) expression, dentate cell proliferation, neurogenesis, astrogliosis, and growth factor content.…”

“…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).…”

“…This variability in dose and latency to the first behavioral seizure in our rats is consistent with previous reports showing that the Sprague Dawley rats show a more variable convulsant response to KA than other rat strains (Golden et al, 1991(Golden et al, , 1995. Thus, while the dose of KA needed to induce SE varied across rats, the SE produced was quite comparable between our CON and SUP rats.We used histopathology scores adapted from a previous report showing protection against histopathology following KA treatment as a result of prenatal choline supplementation (Holmes et al, 2002) to confirm that our KA treatment lead to similar patterns of histopathology between CON and SUP rats. Comparable to Holmes et al (2002), we also found evidence of considerable histopathology from CON rats that experienced KA-induced SE, and this damage also appeared to be attenuated in SUP rats.…”