Biomedical subjects

M B Heaton

Publications and source records attributed to M B Heaton.

At least 37 records · Page 2Linked to original sources

PubMed1997

Immunohistochemical localization of netrin-1 in the embryonic chick nervous system.

Netrin-1 has profound in vitro effects on the growth properties of vertebrate embryonic axons. In addition, netrin-1 mRNA is found in the floor plate of the embryonic nervous system, an intermediate target of many axons, including commissural axons that are affected by netrin-1 in vitro. Moreover, genetic studies of netrin-1 homologs in Caenorhabditis elegans and Drosophila implicate these proteins in commissure formation. We raised polyclonal antisera that recognize chick netrin-1 in fixed tissue sections. The antisera were used to immunohistochemically map netrin-1 in the embryonic spinal cord, brain, and retina. The relationship between netrin-1 localization and the growth of pioneering axons suggests roles for netrin-1 in the regulation of circumferential, commissural, and longitudinal axon growth in the spinal cord and brain. The data also suggest that the primary or sole effect of netrin-1 on pioneering spinal cord commissural axons is haptotactic. Furthermore, the pattern of netrin-1 localization raises the possibility that this protein helps mediate neuronal migration in the spinal cord, brain, and retina.

Animals↗

PubMed1997

Ethanol influences on the chick embryo spinal cord motor system. II. Effects of neuromuscular blockade and period of exposure.

The study described below was performed as a continuation of a previous study in which we found reduced motoneuron number in lumbar spinal cord of the chick embryo following chronic ethanol administration from embryonic day 4 (E4) to E11. We sought to determine whether this reduction was due to primary ethanol toxicity or to enhancement of naturally occurring cell death (NOCD) and to determine whether administration of ethanol at a later period of development could also reduce motoneuron number. Earlier studies have shown that curare suspends NOCD in the chick embryo. By administering both ethanol and curare to these embryos from E4 to E11 and examining the lumbar spinal cord on E12, we determined that ethanol was directly toxic to motoneurons and reduced motoneuron number in the absence of NOCD. By administering ethanol from E10 to E15 and examining the lumbar spinal cord on E16, we determined that ethanol can reduce motoneuron number without altering spinal cord length during more than one stage of chick embryo development, and that ethanol toxicity is not dependent on NOCD. In addition, we demonstrated that ethanol does not affect the neurotrophic content of chick muscle when it is administered from E10 to E15.

Animals↗

PubMed1997

Effects of prenatal ethanol exposure on parvalbumin-expressing GABAergic neurons in the adult rat medial septum.

Exposure of human fetuses to ethanol often results in the fetal alcohol syndrome. Animal models of fetal alcohol syndrome have been developed and used to examine the consequences of prenatal ethanol exposure on the central nervous system. The objective of this study was to determine the long-term effects of prenatal ethanol exposure on parvalbumin-expressing (PA+) GABAergic neurons of the rat medial septum. Pregnant Long-Evans rats were maintained on 1 of 3 diets from gestational day 0 to 21: an ethanol-containing liquid diet in which ethanol accounted for 35% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, or a lab chow control diet. Offspring were killed on postnatal day 60, and their brains were prepared for parvalbumin immunocytochemistry. Female rats exposed to the ethanol-containing diet during gestation had 42% fewer PA+ neurons in the medial septum and reduced PA+ cell density when compared with female rats exposed to the sucrose diet. Ethanol females also had fewer PA+ neurons per unit volume than sucrose females. Male rats exposed to ethanol did not display a similar reduction in PA+ neurons or density. No effect of prenatal diet was found on the area or volume of the medial septum, nor were cell diameters affected. As such, prenatal exposure to ethanol seems to reduce permanently the number of PA+ neurons in the female rat medical septum without affecting area, volume, or neuronal size. Functional implications and possible relations to the fetal alcohol syndrome are discussed.

Animals↗

PubMed1997

Ethanol effects on cultured embryonic hippocampal neuronal calcium homeostasis are altered by nerve growth factor.

The neurotoxic effect of acute ethanol treatment (AET) may lead to an alteration in the regulation of calcium (Ca2+) homeostasis in hippocampal neurons. Ca2+ homeostasis could be affected by AET when neurons are at rest or after depolarizing activity during synaptic transmission. It has been shown that nerve growth factor (NGF) can ameloriate some types of neurotoxicity by stabilizing Ca2+ homeostasis. Previously, we observed that ethanol (EtOH) changed unstimulated (basal) and potassium (K+)-stimulated intracellular calcium ([Ca2+]i) in embryonic septohippocampal neurons (Webb et al., Brain Res. 729:176-189, 1996). The purpose of the present study is to determine the effects of NGF and EtOH on neuronal Ca2+ homeostasis in cultured embryonic hippocampal neurons. The hypotheses tested were the following: EtOH alters Ca2+ homeostasis in hippocampal neurons; NGF modulates Ca2+ homeostasis in hippocampal neurons; and NGF treatment alters the effect of EtOH on [Ca2+]i in hippocampal neurons. Our results indicated that hippocampal neuronal cultures treated with EtOH had lower basal [Ca2+]i than untreated neurons. EtOH decreased K+-stimulated (30 mM KCI) changes in [Ca2+]i in a dose-dependent manner. During K+ stimulation, 20 ng/ml of NGF slowed and reduced the increase in [Ca2+]i. Hippocampal neurons treated with NGF increased or did not change basal [Ca2+]i and did not change or increase K+-stimulated [Ca2+]i in response to EtOH. These responses were dose-related and indicated that NGF could alter the response of hippocampal neurons to EtOH. In conclusion, AET results in the alteration of Ca2+ homeostasis in unstimulated and depolarized cultured embryonic hippocampal neurons. NGF and EtOH independently and collectively affected the regulation of Ca2+ homeostasis in this neuronal population. Changes in [Ca2+]i can disrupt normal cellular function and contribute to cell death. Therefore, alteration of Ca2+ homeostasis may be an underlying mechanism involved in EtOH toxicity. NGF may ameliorate the toxic effects of EtOH by regulating Ca2+ homeostasis.

Animals↗

PubMed1996

Calcium homeostasis in cultured embryonic rat septohippocampal neurons is altered by ethanol and nerve growth factor before and during depolarization.

Ethanol and nerve growth factor (NGF) affect the survival of septohippocampal (SH) neurons. The effect of ethanol and NGF on calcium (Ca2+) homeostasis in these neurons was investigated in this study. Changes in intracellular-free Ca2+ concentration ([Ca2+]i) were measured using indo-1 in cultured embryonic (E21) SH neurons before stimulation (basal) and during stimulation with 30 mM potassium cloride (KCl+). SH neurons were treated with 0, 100, 200, 400, or 800 mg% ethanol with NGF (+NGF) or without NGF (-NGF). NGF treatment decreased, while ethanol did not affect basal [Ca2+]i. The combination of ethanol and NGF treatment led to increases in basal [Ca2+]i. While [Ca2+]i was lower during stimulation with KCl+ following ethanol or NGF treatment, ethanol and NGF treatment together led to significantly greater increases or decreases in [Ca2+]i compared to similarly treated NGF neurons. Responses of SH neurons were compared to those of medial septal (MS) neurons. Changes in [Ca2+]i during treatment with ethanol and/or NGF were reduced in SH neurons compared with MS neurons. We conclude that changes in Ca2+ homeostasis can occur in SH neurons in the presence of ethanol and/or NGF. The changes following ethanol treatment are enhanced by NGF. By altering Ca2+ homeostasis, NGF may enhance the survival of SH neurons during ethanol-induced neurotoxicity.

Animals↗

PubMed1996

Influence of chronic prenatal ethanol on cholinergic neurons of the septohippocampal system.

This study characterized the influence of full-term gestational ethanol exposure on choline acetyltransferase (ChAT)-immunoreactive neurons that project to the hippocampus, within the medial septal (MS) nucleus and the vertical limb of the diagonal band of Broca (DBv). On gestation days 1-22, pregnant dams were fed either a vitamin fortified ethanol-containing liquid diet, pair fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In a previous study, we found that chronic prenatal exposure to ethanol, in this manner, resulted in a significant decline in the ontogenetic upregulation of ChAT activity in the septal area during the second postnatal week, but was followed by recovery to control levels by adulthood. On postnatal days 14 and 60 (P14 and P60) the brains were prepared for ChAT immunocytochemistry. Ethanol exposure had little influence on the number of ChAT-positive neurons in the MS nucleus of animals at either age. Ethanol exposure had no effect on neuronal size or ChAT staining intensity of MS or DBv neurons when compared to chow-fed offspring. Although age-related increases in cholinergic neuronal numbers and decreases in neuronal size were observed between juvenile and adult animals, prenatal ethanol exposure did not appear to influence these postnatal changes in the population as a whole. Overall, these findings suggest that the anatomical maturation of septal cholinergic neurons may be relatively insensitive to prenatal ethanol exposure under conditions of a vitamin-rich dietary supplementation, while biochemical development within this region may be more susceptible to early ethanol influences.

Animals↗

PubMed1996

Influence of prenatal ethanol exposure on cholinergic development in the rat striatum.

This study investigated the influence of ethanol exposure throughout gestation on cholinergic development within the rat striatal region. Pregnant Long-Evans rats were maintained on three diets throughout gestation: A liquid diet in which ethanol accounted for 35-39% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, and a lab chow control diet. At postnatal days 14 and 60 (P14 and P60), the striatal regions of the offspring were analyzed for the number of cholinergic neurons, via choline acetyltransferase (ChAT) immunostaining. The area of the striatum was also measured in these animals. At P14, P21, and P60, ChAT activity was assessed in the same region. These analyses revealed a significant increase in the number of cholinergic striatal neurons at P14 in the animals which had been exposed prenatally to ethanol. This increase was transient, however, with equal numbers of ChAT-positive cells found in all three groups by adulthood (P60). The brain weights of the ethanol-exposed animals were significantly reduced at P14 and P21, but were comparable to controls by P60. There were no significant differences in the striatal area or the overall volume of the region assessed, however, at either P14 or P60. Although there were some increases in ChAT activity across the ages viewed (most notably between P14 and P21), there were no effects of diet on ChAT activity at any age assessed. It is proposed that the increased numbers of cholinergic neurons could be a function of errors in migration, enhanced neurogenesis, diminished cell death, alterations in gene expression, or increased cell survival as a result of alterations in neurotrophic factor production or availability.

Age Factors↗

PubMed1996

Up-regulation of high-affinity neurotrophin receptor, trk B-like protein on western blots of rat cortex after chronic ethanol treatment.

We previously reported that the total neurotrophic activity of hippocampal extracts was significantly (25-50%) reduced after 21-28 weeks of chronic ethanol treatment (CET) [23]. To test whether the level of a neurotrophic factor (i.e., ligand itself) is compromised, we measured nerve growth factor (NGF) protein and NGF mRNA contents using ELISA and Northern analysis. We reported that CET did not appear to reduce NGF protein, NGF mRNA or total neurotrophic activity when measured on sympathetic ganglia neurons [4]. We also observed that both NT-3 mRNA and bFGF mRNA levels were unaffected, but the BDNF mRNA levels was significantly reduced in CET rat hippocampus [18]. Neuronal degeneration and reduction of total neurotrophic activity after CET appear to be induced, at least partially, by compromised transcription of BDNF gene. CET may also induce functional changes in receptors for the neurotrophic factors. To investigate possible changes in neurotrophic factor-receptors, we examined Western blots (immunoblots) of rat cortex after 28 weeks of CET. After sonication and ultra-centrifugation, the supernatant of crude lysates of the cortex from individual animals was subjected to SDS-PAGE, electrotransfered to nitrocellulose membrane, incubated with anti-trk B antibody and secondary antibody conjugated to alkaline phosphatase, and reacted with chemiluminescent substrate. The membranes were then exposed to Kodak XAR film. Compared to controls (n = 6), CET rats (n = 6) appeared to have significantly higher band intensity (P < 0.01) of trk B-like protein at about 145 kDa, which suggests an up-regulation of trk B-like proteins to compensate the compromised level of certain subset (i.e., BDNF or NT-4/5, but not NGF) of neurotrophins in cortex.

Alcoholism↗

PubMed1996

Cultured postnatal rat medial septal neurons respond to acute ethanol treatment and nerve growth factor by changing intracellular calcium levels.

Ethanol neurotoxicity results in the loss of neurons during the development of the nervous system. Nerve growth factor (NGF) can ameliorate the neurotoxic effects of ethanol (EtOH) in rat medial septal (MS) neurons. These experiments study the effects of EtOH and NGF on neuronal calcium (Ca2+) homeostasis in cultured postnatal day of birth (PO) rat MS neurons. Previously, we observed that EtOH and NGF modulate intracellular Ca2+ levels [Ca2+]i) in unstimulated and high potassium stimulated (30 mM KCl) cultured rat embryonic day 21 (E21) MS neurons (Webb et al., Brain Res 701:61-74, 1995). The purpose of the present study was to explore whether the effects of EtOH and NGF on Ca2+ homeostasis were altered by developmental stage. The hypotheses tested were the following: treatment with EtOH affects Ca2+ homeostasis in postnatal day of birth (PO) rat MS neurons by causing transient and persistent changes in [Ca2+]i; NGF modulates Ca2+ homeostasis in MS neurons by regulating [Ca2+]i; the action of NGF changes the response of MS neurons to EtOH, thus altering Ca2+ homeostasis; and that EtOH and/or NGF effects on Ca2+ homeostasis are developmentally regulated. Our results indicated that behaviorally relevant levels of EtOH caused a rapid transient increase in basal [Ca2+]i, whereas there was no effect of NGF on basal [Ca2+]i. Ethanol and NGF interacted, resulting in the lowering of [Ca2+]i. During stimulation with high K+, EtOH inhibited the change in [Ca2+]i. NGF partially ameliorated this effect of higher levels of EtOH, allowing [Ca2+]i to increase. NGF and the lowest level of EtOH potentiated the high K+ stimulated increase in [Ca2+]i. Ethanol and NGF effects on [Ca2+]i were different in the PO neurons compared with our previously published observations in E21 neurons. Therefore, these data suggest that EtOH neurotoxicity and NGF protection involve mechanisms that regulate neuronal Ca2+ homeostasis, and the magnitude of these effects depend on developmental stage.

Animals↗

PubMed1995

Ethanol and nerve growth factor effects on calcium homeostasis in cultured embryonic rat medial septal neurons before and during depolarization.

Ethanol and nerve growth factor (NGF) affect the survival of cholinergic neurons in the rat medial septum. To investigate whether calcium (Ca2+) homeostasis in these neurons is affected by ethanol or NGF treatment, changes in intracellular free Ca2+ concentration ([Ca2+]i) were studied in embryonic (E21) cultured medial septal neurons before stimulation (basal) and during stimulation with high potassium (K+). Changes in [Ca2+]i across time were measured in cultures of neurons treated without ethanol or with 100, 200, 400, or 800 mg% ethanol with NGF (+NGF) or without NGF (-NGF). Changes in [Ca2+]i were analyzed from fluorescence images, using indo-1. The effect of ethanol or NGF treatment was to reduce the rise in basal [Ca2+]i. The combination of ethanol and NGF treatment in +NGF neurons led to increases in basal [Ca2+]i with the greatest increase in basal [Ca2+]i occurring with 200 mg% ethanol. The effect of ethanol or NGF was to increase [Ca2+]i during stimulation with high K+. The greatest increases in [Ca2+]i occurred with 100 and 800 mg% ethanol. Together, ethanol and NGF treatment in +NGF-treated neurons led to significantly greater increases or decreases in K+ stimulated changes in [Ca2+]i compared to similarly treated -NGF neurons. We conclude that in medial septal neurons (before and during depolarization) changes in Ca2+ homeostasis occur in the presence of ethanol or NGF. The changes in [Ca2+]i following ethanol treatment are greater when NGF is present.

Animals↗

PubMed1995

Perturbation of target-directed neurite outgrowth in embryonic CNS co-cultures grown in the presence of ethanol.

Studies were conducted to determine the influence of ethanol on target-directed fiber outgrowth in culture, using embryonic chick spinal cord-muscle, and fetal rat septal-hippocampal co-cultured explants. Process extension from the spinal cord and septal explants in control cultures was selectively oriented toward the appropriate target tissue. Ethanol in the culture medium (500 mg/dl) eliminated this target-oriented outgrowth in both systems, although the overall extent of neurite outgrowth was not affected. In an effort to further characterize the source of this disruption, target explants were grown alone, with and without ethanol, and the target-conditioned culture media was subsequently harvested and placed on newly plated spinal cord or septal explants, to determine whether ethanol decreased the target production of soluble substances. To determine whether deposition of substrate-bound materials by the target tissue was affected by ethanol, spinal cord or septal explants were plated in wells which had previously been occupied by the appropriate target tissue. These studies revealed that ethanol significantly inhibited production of soluble and substrate-bound materials by muscle explants, but not by hippocampal explants. It was concluded that the ethanol-induced loss of target-directed neurite outgrowth in the spinal cord explants could be accounted for primarily by the attenuated production of neurotropic/neurotropic substances by the muscle tissue. The loss of target-directionality in the septal explants appeared to be due to other factors, possibly related to ethanol-induced compromise of the capacity of the septal neurons to respond appropriately to target-derived neurotrophic/neurotropic substances. The implications of these results for the fetal alcohol syndrome are considered.

Animals↗

PubMed1995

Prenatal ethanol exposure alters neurotrophic activity in the developing rat hippocampus.

Extract made from hippocampus of rat pups exposed prenatally to an ethanol-supplemented diet was found to contain more neurotrophic activity at postnatal day 21 than that from animals exposed to control diets, when quantified in a dorsal root ganglion bioassay. This apparent upregulation was specific to hippocampal extract (cerebellar and forebrain/midbrain extracts were also assessed), and to this age (P1, P7, P14 and P60 extracts were also tested). It was suggested that this upregulation may be indicative of, or secondary to, trauma resulting from fetal ethanol exposure. It is speculated that such departures from the normal developmental timetable could contribute to anomalies seen in the fetal alcohol syndrome.

Aging↗

PubMed1995

Alterations in responsiveness to ethanol and neurotrophic substances in fetal septohippocampal neurons following chronic prenatal ethanol exposure.

Pregnant Long-Evans rats were maintained on three diets: a liquid diet in which ethanol accounted for 35-39% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, and a lab chow control diet. At gestation day 18, the fetuses were taken and cultures of septal and hippocampal neurons prepared. Neuronal survival and neurite outgrowth were compared in cultures from the three diet groups, using the following media supplements: ethanol (1.2, 1.8 or 2.4 g/dl), neurotrophic factors (nerve growth factor [NGF] with the septal cultures, basic fibroblast growth factor [bFGF] with the hippocampal cultures), or ethanol plus neurotrophic factors. Both the septal and hippocampal neurons responded to ethanol in a dose-dependent manner. The neurons from both populations from fetuses which had been exposed prenatally to ethanol, however, tolerated considerably higher ethanol concentrations before decreases in survival or outgrowth were seen. These ethanol-exposed neuronal populations were also less responsive to neurotrophic factors: in hippocampal cultures, process outgrowth was significantly enhanced by bFGF in control but not ethanol-derived cultures, and in septal and hippocampal cultures, the neurotrophic factors significantly ameliorated ethanol neurotoxicity in control cultures, but not in those from the ethanol-exposed fetuses. The possible relevance of these observations to the fetal alcohol syndrome is discussed.

Animals↗

PubMed1995

Ethanol influences on the chick embryo spinal cord motor system: analyses of motoneuron cell death, motility, and target trophic factor activity and in vitro analyses of neurotoxicity and trophic factor neuroprotection.

A series of in vivo and in vitro experiments were conducted to determine the influence of prenatally administered ethanol on several aspects of the developing chick embryo spinal cord motor system. Specifically, we examined: (1) the effect of chronic ethanol administration during the natural cell death period on spinal cord motoneuron numbers; (2) the influence of ethanol on ongoing embryonic motility; (3) the effect of ethanol exposure on neurotrophic activity in motoneuron target tissue (limb bud); and (4) the responsiveness of cultured spinal cord neurons to ethanol, and the potential of target-derived neurotrophic factors to ameliorate ethanol neurotoxicity. These studies revealed the following: Chronic prenatal ethanol exposure reduces the number of motoneurons present in the lateral motor column after the cell death period [embryonic day 12 (E12)]. Ethanol tends to inhibit embryonic motility, particularly during the later stages viewed (E9-E11). Chronic ethanol exposure reduces the neurotrophic activity contained in target muscle tissue. Such diminished support could contribute to the observed motoneuron loss. Direct exposure of spinal cord neurons to ethanol decreases neuronal survival and process outgrowth in a dose-dependent manner, but the addition of target muscle extract to ethanol-containing cultures can ameliorate this ethanol neurotoxicity. These studies demonstrate ethanol toxicity in a population not previously viewed in this regard and suggest a mechanism that may be related to this cell loss (i.e., decreased neurotrophic support).

Animals↗

PubMed1995

A method for labeling embryonic rat medial septal region projection neurons, in vitro, using fluorescent tracers.

A retrograde labeling method is described in which rat embryonic (E18, E21) and postnatal (P1) medial septal neurons were labeled with succinyl wheat germ agglutin-fluorescein, fluorescent green microspheres, or 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil) following in vitro hippocampal injections. The brains were removed and immediately immersed in oxygenated Tyrode solution. Dye was pressure injected into the hippocampus bilaterally. After incubating the brain in oxygenated Tyrode, the medial septal region was removed. The neurons were dissociated and cultured at medium density in 35 mm dishes with a hole in the bottom covered by a coverslip with a grid. The neurons were observed with a low light system, and cell counts were made at 5, 24, and 48 h. Labeled and unlabeled neurons showed considerable neurite outgrowth and acetylcholinesterase activity in culture. Highly reproducible labeling was obtained, with Dil giving the best results. Dil labeled the neurons in vitro, was retained during culture for 1 week, and was compatible with cell survival.

Acetylcholinesterase↗

PubMed1995

Chronic prenatal ethanol exposure alters the normal ontogeny of choline acetyltransferase activity in the rat septohippocampal system.

In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown to be especially sensitive to the effects of prenatal ethanol exposure, exhibiting neuronal loss and alterations in neuritic process elaboration. We have characterized the influence of chronic prenatal ethanol treatment (CPET) on the postnatal expression of choline acetyltransferase (ChAT) in the hippocampus and the septal area that contains neurons that provide the primary cholinergic innervation to the hippocampus. On gestation days 1-22, pregnant rats were either fed an ethanol-containing liquid diet, pair-fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In Chow control animals, the ontogenetic progression of ChAT activity in the septal area and hippocampus was characterized by a significant period of upregulation during the 2nd and 3rd postnatal weeks, exhibiting and an approximate 5-fold increase (septal area) and 7-fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure reduced septal and hippocampal ChAT activity levels, compared with those of pair-fed offspring. ChAT activity reached control levels by P21 in ethanol-exposed pups, suggesting that the earlier decline in activity may reflect a delay in the ontogenetic upregulation. In addition, there was a trend toward increased septal and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This liquid diet-stimulated increase may mask the effects of ethanol on early postnatal ChAT expression in the septohippocampal system. The results suggest that prenatal ethanol exposure may influence factors that regulate the developmental expression of ChAT in the septohippocampal system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

In vitro comparison of the effects of ethanol and acetaldehyde on dorsal root ganglion neurons.

Results of previous experiments designed to investigate the role of acetaldehyde, the primary metabolite of ethanol, have been contradictory. Experiments have provided evidence that supports and refutes the idea that acetaldehyde is responsible for the teratogenic effects observed in fetal alcohol syndrome. In the present study, cell culture techniques were used to examine the effects of acetaldehyde, both independently and in conjunction with ethanol. The purpose was to determine whether acetaldehyde had any effect on survival and process outgrowth of dorsal root ganglion (DRG) neurons cultured in vitro. This study revealed that acetaldehyde was as toxic to DRG survival as is ethanol, but had a lesser effect on neurite outgrowth than ethanol. Also, acetaldehyde and ethanol do not act synergistically to damage neurons in culture. The results indicate that, although acetaldehyde is probably not solely responsible for ethanol neurotoxicity, it does exhibit a secondary toxicity that could be the subject of future studies.

Acetaldehyde↗

PubMed1994

Responsiveness of cultured septal and hippocampal neurons to ethanol and neurotrophic substances.

Dissociated septal and hippocampal neurons from E18 fetal rats were cultured with varying concentrations of ethanol (0.6-2.4 g/dl) and in cultures containing ethanol plus nerve growth factor (NGF) or basic fibroblast growth factor (bFGF). These substances have been shown to provide neurotrophic support for these populations and to afford neuroprotection against certain toxic substances or conditions applied to some neuronal populations. Both the septal and hippocampal neurons responded to ethanol in a dose-dependent manner. Survival of septal neurons was generally unaffected by initial ethanol concentrations of 0.6 and 1.2 g/dl but was considerably impaired by higher concentrations (1.8 and 2.4 g/dl), while neurite outgrowth was compromised by all ethanol concentrations except the lowest one applied. The hippocampal neurons survived ethanol concentrations up to 2.4 g/dl, although process extension was decreased in concentrations of 1.2 g/dl and higher. NGF or bFGF in the culture medium (in cultures without ethanol) did not affect neuronal survival or process outgrowth in either population, probably owing to the relatively high plating densities of the cultures. NGF did tend to have a moderate ameliorative effect on the ethanol neurotoxicity in the septal cultures, however, and was slightly effective in this regard in hippocampal cultures at intermediate ethanol concentrations (1.8 g/dl). High concentrations of ethanol (2.4 g/dl) reduced the proportion of cholinergic cells in the septal preparations by approximately 50%. This neuronal loss could be reversed by inclusion of high concentrations of NGF in the culture medium (100 ng/ml) but not by a lower concentration (20 ng/ml). bFGF provided some protection against ethanol cytotoxicity with respect to both populations. The implications of these results for studies of fetal alcohol effects are discussed, as well as their relation to prior reports of trophic factor neuroprotection.

Acetylcholinesterase↗