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

Abstract

Prenatal choline supplementation (SUP) protects adult rats against spatial memory deficits observed after excitotoxin-induced status epilepticus (SE). To examine the mechanism underlying this neuroprotection, we determined the effects of SUP on a variety of hippocampal markers known to change in response to SE and thought to underlie ensuing cognitive deficits. Adult offspring from rat dams that received either a Control or SUP diet on embryonic days 12-17 were administered saline or kainic acid (i.p.) to induce SE and were euthanized 16 days later. SUP markedly attenuated seizure-induced hippocampal neurodegeneration, dentate cell proliferation, hippocampal GFAP mRNA expression levels, prevented the loss of hippocampal GAD65 protein and mRNA expression, and altered growth factor expression patterns. SUP also enhanced pre-seizure hippocampal levels of BDNF, NGF, and IGF-1, which may confer a neuroprotective hippocampal microenvironment that dampens the neuropathological response to and/or helps facilitate recovery from SE to protect cognitive function. Keywords choline; kainic acid; hippocampus; seizures; bromodeoxyuridine; growth factor; glutamic acid decarboxylase; glial fibrillary acidic protein; neuroprotection Status epilepticus (SE), a period of prolonged seizures, produces a host of plastic changes in the hippocampus that are thought to contribute to the development of temporal lobe epilepsy. SE results in substantial neuronal loss (Cavazos et al., 1994;Haas et al., 2001;Gorter et al., 2003), γ-aminobutyric acid (GABA) system alterations (e.g., Houser & Esclapez, 1996), reactive gliosis (Jorgensen et al. 1993; Niquet et al., 1994a;Kang et al., 2006), mossy fiber innervation of the dentate gyrus (Sutula et al., 1988;Ben-Ari & Represa, 1990), changes in levels of growth factors (Khrestchatisky et al., 1995;Mudo et al., 1996;Schmidt-Kastner et al., 1996;Shetty et al., 2004), and a transient increase in cell proliferation and neurogenesis (Bengzon et al., 1997;Parent et al., 1997;Scharfman et al., 2000;Hattiangady et al., 2004). These SE-induced degenerative and regenerative changes in the hippocampus are also Corresponding author: Dr. Christina L. Williams, Department of Psychology and Neuroscience, 572 Research Drive, Box 91050, GSRB-II, Room 3022, Duke University, Durham, NC 27708, USA, Phone: 919-660-5638, Fax: 919-660-5798, Email: williams@psych.duke.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. accompanied by deficits in hippocampal-dependent learning and memory (Stafstrom et al., 1993;Liu et al., 1994;Sarkisian et al., 1997;Hort et al., 1999;Mik...

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“…Indeed, certain aspects of cholinergic metabolism in brain (specifically, acetylcholinesterase and high-affinity choline uptake) and behavior have been shown to be enhanced in DEF rats (e.g., Blusztajn et al 1998;Cermak et al 1998;Williams 1999, 2003;Wong-Goodrich et al 2008b). Additionally, although hippocampal slices from DEF rats show increased thresholds for the induction of LTP (Pyapali et al 1998;Jones III et al 1999), it is not a trivial point that all slices showed LTP, i.e., DEF rats still have an active hippocampus, albeit with altered function.…”

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease

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