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Prenatal alcohol exposure (PAE) has been shown to alter the somatosensory cortex in both human and animal studies. In rodents, PAE reduced the size, but not the pattern of the posteromedial barrel subfield (PMBSF) associated with the representation of the whiskers, in newborn, juvenile, and adult rats. However, the PMBSF is not present at birth, but rather first appears in the middle of the first postnatal week during the brain growth spurt period. These findings raise questions whether early postnatal alcohol exposure might disrupt both barrel field pattern and size, questions that were investigated in the present study. Newborn Sprague-Dawley rats were assigned into alcohol (Alc), nutritional gastric control (GC), and suckle control (SC) on P4. Rat pups in Alc and GC were artificially fed with alcohol and maltose-dextrin dissolved in milk respectively, via an implant gastrostomy tube, from postnatal day 4 (P4) to P9. Pups in the Alc group received alcohol (6.0 g/kg) in milk, while the GC controls received isocaloric equivalent maltose-dextrin dissolved in milk. Pups in the SC group remained with their mothers and breast fed throughout the experimental period. On P10, pups in each group were weighed, sacrificed, and their brains removed and weighed. Cortical hemispheres were separated, weighed, flattened, sectioned tangentially, stained with cytochrome oxidase, and PMBSF measured. The sizes of barrels and the interbarrel septal region within PMBSF, as well as body and brain weights were compared between the three groups. The sizes of PMSBF barrel and septal areas were significantly smaller (p < 0.01) in Alc group compared to controls, while the PMBSF barrel pattern remained unaltered. Body, whole brain, forebrain, and hemisphere weights were significantly reduced (p < 0.01) in Alc pups compared to control groups. GC and SC groups did not differ significantly in all dependent variables, except body weight at P9 and P10 (p < 0.01). These results suggest that postnatal alcohol exposure, like prenatal exposure, significantly influenced the size of the barrel field, but not barrel field pattern formation, indicating that barrel field pattern formation consolidated prior to P4. These results are important for understanding sensorimotor deficits reported in children suffering from fetal alcohol spectrum disorder (FASD).
Exposure to alcohol during prenatal development has been shown to lead to growth retardation, facial dysmorphology, and brain anomalies in humans (Jones and Smith, 1973; Jones and Smith, 1975), collectively referred to as fetal alcohol syndrome [FAS] (Clarren and Smith, 1978; Connor et al., 2006; Streissguth et al., 1991; Streissguth et al., 1984). These anomalies have also been reported in rodents exposed to alcohol during gestation and/or during the early postnatal period (Lopez-Tejero et al., 1986; Mattson et al., 2001; Tran et al., 2000). The behavioral deficits seen in offspring of mothers that abuse alcohol during pregnancy as well as in rodents exposed to alcohol during gestation and early postnatal periods indicate that the sensorimotor system is particularly susceptible to alcohol during brain development. Children with FAS have delayed motor development and somatosensory impairments necessary for performance of fine and gross motor skills (Burd et al., 2003; Connor et al., 2006; Lopez-Tejero et al., 1986). Exposure to alcohol during brain development has been shown to affect reaction time, attention, and response latency in children with FAS (Streissguth et al., 1984). In rodents, prenatal exposure to alcohol disrupted the distribution of callosal projection neurons in first somatosensory cortex (SI) (Miller, 1997), significantly decreased somatosensory cortical volume, total neuron and glial cell numbers (Miller and Potempa, 1990), and resulted in significant structural and metabolic alterations in rat cerebral cortex (Miller and Dow-Edwards, 1988; Miller and Dow-Edwards, 1993). Similarly, early postnatal alcohol exposure decreased brain weight (Bonthius and West, 1991; Maier et al., 1999), reduced neocortical volume (Mooney and Napper, 2005), and reduced the size of neocortex (Miller, 1996) in rats.
The stages of brain development are similar in both humans and rodents, except for their timing with respect to birth. The full gestation period (prenatal life) in rodents is equivalent to the first and second trimesters, while postnatal day one (P1) to P10 corresponds roughly to the third trimester in humans (Bayer et al., 1993). Thus, exposure of rodents to alcohol during pre-and postnatal periods is expected to produce similar deficits as seen in offspring of human mothers who abuse alcohol during pregnancy. Since the brain undergoes regional differences in growth, genesis, migration and proliferation of various neuronal cell types during development, the nature of anatomical anomalies and functional deficits seen in animals and humans exposed to alcohol early in life are dependent on the period of the exposure. Rats exposed to alcohol during either the latter half of gestation, throughout gestation, or the early postnatal period had significant reductions in body and brain weights compared to those exposed to alcohol during the early gestational period (Tran et al., 2000). These findings show that the latter half of gestation and the early postnatal period, which are analogous to the second and third trimesters of pregnancy in humans, constitute critical periods of vulnerability of brain to the deleterious effects of alcohol.
The rodent barrel field in layer IV of SI consists of clusters of cells, called barrels, that are organized into larger subfields associated with the representation of the body surface (Welker and Woolsey, 1974). One subfield, the posteromedial barrel subfield (PMBSF) is associated with the representation of large mystacial vibrissae on the contralateral face (Welker and Woolsey, 1974). The presence of barrels in PMBSF is dependent on thalamocortical afferents from the ventral posterior medial nucleus (VPM) of the thalamus. VPM receives input from the principal trigeminal nucleus that in turn receives input from deep vibrissal nerves (Rice, 1995). The first postnatal week is a critical period for barrel field development since the barrel field is not present until P3 (McCandlish et al., 1989) and requires an intact periphery for development of a normal barrel field pattern. (Dawson and Killackey, 1987; Waters et al., 1990).
The PMBSF has recently been used as a model system to study the effects of prenatal alcohol exposure (PAE) on barrel field organization and development. PAE has been reported to delay the development of PMBSF and limb barrel subfields by 1–2 days (Margret et al., 2006), reduce total PMBSF area and sizes of individual barrels within the PMBSF in rats (Margret et al., 2005b) and mice (Powrozek and Zhou, 2005), and delay thalamocortical afferents from reaching presumptive barrel field cortex (Margret et al., 2005a). Since the first postnatal week also constitutes a critical period for brain vulnerability to alcohol exposure (Tran et al., 2000), as well as a critical period of development of the PMBSF barrel field in rodents (Killackey and Belford, 1979; Margret et al., 2006; McCandlish et al., 1989; Rice, 1995; Rice and Van der Loos, 1977; Wu and Gonzalez, 1997), it was unknown whether early postnatal alcohol exposure would alter barrel field pattern formation and/or barrel field size. In the present study, we extended our previous PAE findings (Margret et al., 2005b) to an examination of effects of postnatal alcohol exposure on barrel field size and pattern in rat PMBSF.
The Texas A&M University Laboratory Animal Care Committee approved all procedures prior to the start of the experiment. All animal care procedures were performed under the minimal standards set forth by the NIH Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80-23).
Twenty-eight male and female rat pups derived from 8 timed-pregnant adult female Sprague Dawley rats were used in this study. Pregnant female rats were generated on-site (Texas A&M University) and housed individually for the duration of pregnancy. On the day following birth, litters were culled to 10 (equal gender when possible) and fostering methods were used to maintain litters between 8-10 pups from P1 to P4 (the day of surgery).
There were three treatment groups: alcohol (Alc, 6.0 g/kg/day; n=10), nutritional gastrostomy control (GC; n=10), and suckle control (SC; n=8). Whenever possible, all three treatment groups were represented within one litter and no more than 2 pups (one of each gender) from the same litter were placed into the same treatment group. All pups remained with their untreated, lactating dams until they were randomly assigned into the three treatment groups at P4; fostering methods were used to maintain the litter size at a minimum of 8 pups. The pups in Alc and GC groups were artificially reared. Those in Alc group received two, 20-minute infusions of milk diet containing 3.0 g/kg of alcohol (for a total of 6.0 g/kg/day) separated by a 100-minute interval every day from P4 until P9. The alcohol-containing feedings occurred at the same time each day and consisted of 2 consecutive feedings of the 12 regularly scheduled feedings that occurred over each 24 hour period. Pups assigned to the GC group received the identical feeding regimen as those assigned to the Alc group, except that alcohol diet was replaced by an isocaloric equivalent maltose-dextrin dissolved in the diet. Non-treatment feedings (10 consecutive feedings within every 24 hour period) contained milk diet only and were administered beginning 4 hours following the first alcohol or maltose dextrin feeding and continued in 100-minute intervals until the next assigned treatment period or scheduled sacrifice. Pups in SC group remained with their mothers until time of sacrifice at P10.
On P4, pups in Alc and GC groups underwent simple surgery under isoflurane anesthesia to implant the gastrostomy tube for the delivery of daily nutritional requirements. Complete surgical details and artificial-rearing techniques have been published elsewhere (West et al. 1984). Following recovery from surgery, rat pups were placed into plastic cups containing aspen shavings and a piece of artificial fur, and the cups were floated in an aerated, heated water bath maintained at 36°–37° C. All pups from the same litter were placed in the same water bath. Main feeding lines connected the gastrostomy tube of each pup to formula-filled syringes, which were placed into an infusion pump (Harvard Apparatus, Holliston, MA, Model #935). The pumps were timer-activated once every 2 hours and administered 1/12 of the daily amount of formula to the pups over a 20-minute period. The artificially reared pups received their daily formula requirements in 12 feedings (two consecutive feedings with either alcohol or maltose dextrin equivalent and 10 regularly scheduled feedings with milk diet) with a 100-minute interval between feedings. The amount of formula given to the pups was determined by calculating 33% of the mean body weight of all littermates, which included both alcohol and control pups.
Pups in each group were sacrificed on P10, at the beginning of the next scheduled treatment feeding, with an overdose of Euthasol® (Webster Veterinary Supply Inc., Houston, TX) and perfused intracardially with physiological saline followed by 4% paraformaldehyde in 0.1 M phosphate buffer (pH=7.4). Each brain was removed carefully from the cranial cavity, weighed, and placed in buffer, and shipped overnight. The next day the cortical hemispheres were cut, the underlying white matter was separated from cortex, hemispheres were weighed, flattened between two Plexiglas plates, and refrigerated overnight in 4% paraformaldehyde solution (Waters et al., 1990). The flattened cortices were sectioned tangentially on a Vibratome at 100 μm-thickness and placed in containing 0.01 M potassium phosphate buffer solution (KPBS, pH 7.4, 21°C). To visualize the barrel field, sections were reacted with cytochrome oxidase, mounted on gelatin-coated slides, and cover slipped (Waters et al., 1995; Wong-Riley and Welt, 1980).
All blood samples were taken on P6 at 90 minutes following the onset of the second alcohol or maltose dextrin infusion for artificially reared pups. Although multiple blood samples were not taken and analyzed, based on previous research, (Bonthius et al., 1988; Bonthius and West, 1988; Kelly et al., 1987), sampling at this time point corresponds to the peak blood alcohol concentration in this experimental paradigm. Identical blood collection procedures were applied to the respective GC pups to control for any stress induced by the sampling procedure. Twenty (20) μl of blood was taken from each animal by producing a small nick to the tip of the tail. The samples were immediately placed into individual glass vials containing 200 μl of a cocktail composed of 0.6 N perchloric acid and 4 mM n-propanol in double distilled water, tightly fastened with a septum sealed lid, and stored at room temperature until analysis by head space gas chromatography (Varian, Palo Alto, CA, Model 3900).
The animals used in this experiment were raised, treated, sacrificed at Texas A & M University, and the brain tissue was shipped to the senior author's lab post mortem, therefore the treatment identity of the animals was unknown at the time of processing and measurement. The treatment code was broken only after the final measurements were taken.
Quantitative morphometric analysis has been previously described (Margret et al., 2005b). In brief, the twenty-seven well-defined posteriorly located PMBSF barrels (4 straddler barrels, 4 barrels in row A, 4 in row B, 5 in row C, 5 in row D and 5 in row E) were examined under a light microscope, digitized, and reconstructed using Adobe Photoshop (version 7.0). In most cases, the entire barrel field was confined to three or four sections. Barrels from adjacent sections were aligned using blood vessels as fiducials and a single image was reconstructed and used for area measurements. A line was fitted around the 27 PMBSF barrels and the area was measured using Image J (NIH). The sizes of individual barrels within the PMBSF were also reconstructed from adjacent sections. Measures included total barrel field area (27 barrels), areas of individual barrels, and the area of septal regions between barrels. Repeated measures ANOVA was used for comparing body weights with treatment and postnatal day as the independent variables, while one-way ANOVA was used for comparing brain weights, and areas of PMBSF barrels and septa among the treatment groups. Significant main effects were followed by Fisher's PLSD tests for pair-wise comparisons across all groups means with the level of significance set at 0.05. Statview (5.1) or DataDesk (6.1) were used to perform all statistical analyses.
The mean peak BACs for the blood samples taken from pups at 90 minutes after the start of the second alcohol feeding was 294.3 (±8.9 S.E.M.) mg/dl for pups in the Alc group.
The total PMBSF area was demarcated by enclosing the 27 barrels with a line and an example of this is shown in the reconstruction in Fig. 1′ for an Alc pup. The total averaged PMBSF area [F(2,25) = 25.34, P<.001], total averaged individual barrel area [F(2,25) = 10.46, p < 0.01], and total averaged septal area [F(2,25) = 11.71, p < 0.01] were significantly reduced in Alc pups compared to GC and SC pups. The mean and standard error of the mean for each PMBSF size measurement are presented in Table 1. Normalization of data showed that total averaged PMBSF area, total averaged barrel area, and total averaged septal area were reduced 17.6%, 11.0%, 26.3%, respectively in Alc pups compared to SC pups. A photomicrograph and line-drawing reconstruction of the PMBSF from each treatment group are shown in Fig. 1. Note the appearance of the five rows of whisker barrels (A–E), four straddler barrels (α,β,γ,δ), and total 27 barrels that comprise the PMBSF. Postnatal alcohol exposure from P4 to P10 did not disrupt the overall barrel pattern or number of barrels within the PMBSF.
The whole brain [F(2,25) = 86.04, p < 0.01], forebrain [F(2,25) = 86.20, p < 0.01], and hemispheric [F(2,25) = 67.98, p < 0.01] weights were significantly lower in the Alc group compared to either GC or SC groups (p < 0.01), but no significant differences were found between GC and SC groups. These data are presented in Table 2. When the combined averaged weight of left and right hemispheres were compared in each group, no significant differences were found for treatment groups. Therefore, the combined hemisphere weight was averaged for each animal. The hemispheres of rats in Alc group weighed significantly less compared to either GC or SC group (p < 0.01). No significant differences were observed between the two control groups. Normalization of these data showed that whole brain, forebrain, and hemispheric weights were reduced 28.6%, 27.7%, 30.6%, respectively in Alc pups compared to SC pups.
Body weights of pups in the various groups increased dissimilarly from P4 to P10 and these data are shown in Table 3. There was a significant effect of treatment on body weight by day as measured using an ANOVA repeated measures analysis ([F(6,150) =1117.05, p < 0.01]. There was no difference among the treatment groups in weight gain from P4 to P6, however, on each of P7 to P10, the pups in the Alc group weighed significantly less than those of the GC or SC groups [Day P7 – F(2,25) = 4.13, p < 0.05; Day P8 – F(2,25) = 8.36, p < 0.01; Day P9 – F(2,25) = 11.88, p < 0.01; Day P10 – F(2,25) = 16.99, p <0.01]. Normalization of these data as a percent reduction from SC at P10 showed that Alc pups were 18.3% lower than the averaged body weight of SC pups.
Forebrain weight and total PMBSF area were significantly reduced in postnatal alcohol exposed pups. A Pearson Product-Moment Correlation (r), linear regression analyses (t-ratio), and probability measure (p) were used to compare forebrain weight with total PMBSF area for each treatment group. Only the Alc group showed a significant correlation (r = 0.78, t = 3.57, p = 0.007), while neither PF (r = −0.23, t = −0.67, p = 0.52) nor SC (r = 0.66, t = 2.16, p = 0.074) treatment groups were significantly correlated. Similarly, averaged hemisphere weight and PMBSF area were significantly correlated for the Alc group (r = 0.75, t = 3.27, p = 0.011), but not for PF (r = −0.54, t = −1.80, p = 0.11) or SC (r = 0.29, t = 0.76, p = 0.48) groups.
In this study, we exposed young rat pups to alcohol during the third-trimester equivalent (P4 through P10), which included the period of the brain-growth-spurt (Pierce et al., 1989), and measured changes in vibrissae barrel cortex, as well as in brain and body weights. The important findings were that postnatal alcohol exposure significantly reduced the averaged total area of the PMBSF, the sizes of individual barrels within the PMBSF, the septal regions within the PMBSF, but failed to disrupt the general barrel pattern. Furthermore, brain and body weights were significantly reduced in alcohol-exposed pups relative to the controls. These results were similar to previous reports of reductions in barrel cortex following gestational alcohol exposure (Margret et al., 2005b).
The averaged area of PMBSF barrel field in SI was significantly smaller in alcohol treated pups compared to controls. This observation supports the reported decreases in volume of the cerebral cortex in humans and animals exposed to alcohol during brain development (Mooney and Napper, 2005; Olney et al., 2002; Sowell et al., 2002; Young et al., 2003). Taken together, the findings in the present and previous studies provide evidence that the early postnatal period, which is the period of brain growth spurt that is analogous to the third trimester of pregnancy in humans, is a critical period of vulnerability to alcohol neurotoxicity in cerebral cortex, as it appears to be for many other brain regions. (Livy et al., 2001; Livy et al., 2003; Maier et al., 1999; Maier and West, 2003; Tran and Kelly, 2003). Interestingly, PAE also reduced the size of the PMBSF and sizes of individual barrels in neonatal pups (Margret et al., 2005b), however in postnatal alcohol exposed pups, averaged PMBSF and individual barrel sizes were approximately 8% smaller than in PAE pups suggesting that both pre-and-postnatal periods are important for barrel field development.
Mechanisms underlying alcohol-induced anomalies in cerebral cortex during cortical development are multifaceted, and include alterations in cortical structure (Granato et al., 1995; Santarelli et al., 1995), DNA and protein contents (Miller, 1996), neurotrophin and apoptotic factors (Climent et al., 2002; Heaton et al., 2003a; Moore et al., 2003), as well as promotion of cell death (Ikonomidou et al., 2000; Miller, 2006). Since the appearance and maturity of thalamic barreloids, cortical barrel field in layer IV of SI, and functional maturation of thalamocortical and corticocortical afferents occur during the early neonatal period, exposure to alcohol during this period may disrupt thalamocortical connectivity (Rice, 1995; Rice and Van der Loos, 1977) and subsequently lead to anatomical anomalies in SI. For example, exposure of rats to alcohol during gestation has been shown to affect the terminal arborization of thalamocortical and corticothalamic projections (Granato et al., 1995; Santarelli et al., 1995), and delay thalamocortical afferents from reaching presumptive barrel cortex (Margret et al., 2005a). Alcohol exposure has also been reported to decrease metabolic activity within developing cerebral cortex of rodents (Miller and Dow-Edwards, 1988; Miller and Dow-Edwards, 1993). Furthermore, alcohol exposure lowers DNA and protein content in developing rodent brains (Miller, 1996). These factors can interfere with development and cell maturation, as well as dendrogenesis and synaptogenesis within cerebral cortex. In addition to alcohol-induced structural and metabolic anomalies in cerebral cortex, alcohol exposure has been shown to influence cell survival, cell death, neurite growth, and synaptogenesis. For instance, gestational alcohol exposure reduced the levels of neurotrophic factors and their signaling pathways that are important for cell survival (Climent et al., 2002; Heaton et al., 2003a; Heaton et al., 2003b; Moore et al., 2003) and elevated apoptosis-related proteins and oxidative processes (Climent et al., 2002; Heaton et al., 2003c). Taken together, alcohol-induced biochemical and cellular changes during brain developmental are likely responsible for reductions in brain weight and PMBSF barrel area observed in the alcohol group in the present study. It is clear that alcohol exposure during the critical growth spurt period has significant effects on cortical development. The alcohol-induced dysfunctions in cerebral cortex reported during the period of synaptogenesis contribute, in part, to impaired sensory information processing that may underlie delayed sensorimotor development and impaired fine and gross motor control seen in children with FASD (Burd et al., 2003; Connor et al., 2006; Lopez-Tejero et al., 1986; Streissguth et al., 1984).
Prenatal (Margret et al., 2005b) and postnatal alcohol exposure reduced body and brain weights and size of the barrel field but did not alter barrel pattern. The barrel field is not present at birth, but develops differentially over the first postnatal week (McCandlish et al., 1989) and requires an intact periphery for development of a normal barrel pattern (Dawson and Killackey, 1987; Waters et al., 1990). Vibrissae barrels appear first on P3 followed by forelimb barrels on P5 and hindlimb barrels on P6 (Margret et al., 2006; McCandlish et al., 1989). Prenatal alcohol exposure delays the development of the barrel field but not at the expense of disrupting the barrel pattern (Margret et al., 2006). PAE also delays the timing of thalamocortical axons from reaching barrel cortex (Margret et al., 2005a). In the present study, postnatal alcohol administration began on P4, well after barrel field consolidation takes place, and it is possible that fetuses and neonates were not exposed to alcohol during a potentially important window for barrel field pattern formation. Studies are underway to further test this hypothesis.
Our data showed that postnatal alcohol exposure significantly reduced the size of the PMBSF, sizes of individual cortical barrels, and sizes of intervening septae. The PMBSF located in parietal cortex is responsible for processing sensory information and an alteration in size likely reflects reduced sensitivity to the environment. The PMBSF lies within a cortical column that forms a basic functional unit of the neocortex (Keller, 1995). In the six-layered cortical column in parietal cortex in SI, layer IV neurons receive segregated input from sensory thalamus and relay that information to locations within and outside the column. Only in rodent SI, does this segregated input terminate in layer IV barrels associated with punctate regions of the periphery; segregated inputs are common features of neocortex. Cortical barrels within the PMBSF receive one-to-one input from specific vibrissae on the contralateral face and provide the major somatosensory input for the rodent to navigate through its environment (Welker and Woolsey, 1974). Output from barrel columns project, in part, to motor cortex where it serves to modulate motor output (Hoffer et al., 2003). Barrel size depends on thalamocortical input and a smaller barrel field and barrels reported here likely reflect diminished cortical sensitivity and reduced sensory feedback to motor cortex. Children with FASD have s maller parietal cortices (Riley et al., 2004), perform poorly on sensorimotor tasks (Connor et al., 2006), and often exhibit peripheral malformations (Spiegel et al., 1979).
Barrel field formation occurs during the first postnatal week and requires precise timing of thalamocortical afferents onto barrel field target neurons relaying input from an intact periphery. Our data demonstrated that postnatal alcohol exposure between P4 and P10 did not alter the barrel pattern, confirms that thalamocortical axons reached their correct cortical targets. A disrupted barrel pattern would have provided a mismatch between sensory input and motor output that might underlie fine motor dysfunctions reported in children with FASD (Connor et al., 2006).
The progressive increases in body weight across all groups, is similar to weight growth curves reported in previous studies (Goodlett and Johnson, 1997; Thomas et al., 2003; Tomlinson et al., 1998). The increase in alcohol-treated group was significantly less than in GC and SC groups, which is in agreement with the results of similar studies (Thomas et al., 2003; Tomlinson et al., 1998; Tran et al., 2000). In contrast, other investigators have reported no significant weight loss in rats exposed to alcohol during early postnatal period (Chen et al., 1999; Chen et al., 1998). The significant weight reduction in alcohol-treated pups in the current study might not be due solely to alcohol exposure, but rather to combined effects of alcohol and method of feeding. For example, rats in GC group have been shown to weigh significantly less than those in SC group on P9 (Chen et al., 1998; Thomas et al., 2003).
The observed significant reductions in the weights of whole brain, forebrain, and hemispheres are consistent with the findings in previous studies in which rodents were exposed to alcohol during the early postnatal period (Bonthius and West, 1988; Chen et al., 1999; Chen et al., 1998; Miller, 1996; Moore et al., 2003). In addition to reductions in whole brain and hemisphere weights, the hippocampus and cerebellum are also vulnerable to alcohol exposure from P4 to P12 (Miller, 1996). However, the findings in the current and previous studies are at odds with the recently reported lack of significant main effects of alcohol on forebrain weight at P10 (Mooney and Napper, 2005). This discrepancy may be due to the differences in alcohol exposure paradigms, which could influence blood alcohol concentration (Bonthius et al., 1988; Bonthius and West, 1988; Bonthius and West, 1991).
In the present study, postnatal alcohol exposure reduced PMBSF area, as well as body and brain weights. Forebrain and hemisphere weights were significantly correlated with PMBSF area in postnatal alcohol exposed rats, but not for the other treatment groups. These results might be interpreted to support the view that postnatal alcohol exposure results in a global reduction rather than having a specific effect on the barrel field. While this possibility cannot be ruled out, it is important to note that gestational alcohol exposure similarly reduced body and brain weights and PMBSF size in neonatal rats (Margret et al., 2005b), but only barrel field measures, and not body or brain weights, were significantly reduced in adult rats that were also exposed to alcohol during gestation (Chappell et al., 2007). In neonatal mice, only PMBSF size, and not body or brain weights or brain volume, was significantly reduced suggesting that the barrel field is vulnerable to gestational alcohol exposure (Powrozek and Zhou, 2005). Therefore, brain weight in itself may not be the best measure to use for comparisons of structural relationships since brain weight depends on cell density. In a recent study, brain weight, body weight, and barrel field size were measured in recombinant inbred mice (BXD) and C57BL/6J and DBA/2J progenitors; DBA/2J mice had larger barrel field areas than C57BL/6J and several BXD strains, despite the fact that DBA/2J mice had smaller average body and brain weights (Li et al., 2005). What remains to be determined is whether the effects of postnatal alcohol exposure on body weight, brain weight, and barrel field size continue to manifest themselves in juvenile and adult rats or as in the case of gestational alcohol exposure, only the barrel field appears to suffer long-term deficits.
Supported by a grant (RO1AA013437) from NIAAA to R.S.W. and A.J.E. and AA10090 to J.R.West
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