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Binge ethanol exposure during adolescence leads to a persistent loss of neurogenesis in the dorsal and ventral hippocampus that is associated with impaired adult cognitive functioning.

Vetreno RP, Crews FT - Front Neurosci (2015)

Bottom Line: This reduction in neurogenesis was accompanied by a concomitant reduction in proliferating cells (Ki-67) and an increase in cell death (cleaved caspase-3).In the hippocampus, AIE treatment induced a long-term upregulation of neuroimmune genes, including Toll-like receptor 4 (TLR4) and its endogenous agonist high-mobility group box 1 as well as several proinflammatory signaling molecules.Interestingly, object recognition memory was positively correlated with DCX + IR in both the dorsal and ventral hippocampal dentate gyrus while latency to enter the center of the apparatus was negatively correlated with DCX + IR in the ventral dentate gyrus.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina Chapel Hill, NC, USA.

ABSTRACT
Adolescence is a developmental period that coincides with the maturation of adult cognitive faculties. Binge drinking is common during adolescence and can impact brain maturation. Using a rodent model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 20% EtOH w/v; 2 days on/2 days off from postnatal day [P]25 to P55), we discovered that AIE treatment reduced neurogenesis (i.e., doublecortin-immunoreactive [DCX + IR] cells) in both the dorsal and ventral hippocampal dentate gyrus of late adolescent (P56) male Wistar rats that persisted during abstinence into adulthood (P220). This reduction in neurogenesis was accompanied by a concomitant reduction in proliferating cells (Ki-67) and an increase in cell death (cleaved caspase-3). In the hippocampus, AIE treatment induced a long-term upregulation of neuroimmune genes, including Toll-like receptor 4 (TLR4) and its endogenous agonist high-mobility group box 1 as well as several proinflammatory signaling molecules. Administration of lipopolysaccharide, a gram-negative endotoxin agonist at TLR4, to young adult rats (P70) produced a similar reduction of DCX + IR cells that was observed in AIE-treated animals. Behaviorally, AIE treatment impaired object recognition on the novel object recognition task when assessed from P163 to P165. Interestingly, object recognition memory was positively correlated with DCX + IR in both the dorsal and ventral hippocampal dentate gyrus while latency to enter the center of the apparatus was negatively correlated with DCX + IR in the ventral dentate gyrus. Together, these data reveal that adolescent binge ethanol exposure persistently inhibits neurogenesis throughout the hippocampus, possibly through neuroimmune mechanisms, which might contribute to altered adult cognitive and emotive function.

No MeSH data available.


Related in: MedlinePlus

Adolescent intermittent ethanol (AIE) treatment leads to long-term deficits in object recognition memory. (A) Latency to enter the center of the open-field apparatus during the first trial, which provides a measure of thigmotaxis, was significantly increased in adult rats following AIE treatment. (B) Adolescent intermittent ethanol treatment significantly reduced the discrimination index, which is indicative of impaired object recognition memory, in adult rats relative to CONs. Data are presented as mean ± SEM. *indicates p < 0.05; **indicates p < 0.01, relative to CON rats.
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Figure 6: Adolescent intermittent ethanol (AIE) treatment leads to long-term deficits in object recognition memory. (A) Latency to enter the center of the open-field apparatus during the first trial, which provides a measure of thigmotaxis, was significantly increased in adult rats following AIE treatment. (B) Adolescent intermittent ethanol treatment significantly reduced the discrimination index, which is indicative of impaired object recognition memory, in adult rats relative to CONs. Data are presented as mean ± SEM. *indicates p < 0.05; **indicates p < 0.01, relative to CON rats.

Mentions: Previous studies found that adolescent binge ethanol treatment of mice reduces object recognition memory 3 weeks after ethanol treatment (Pascual et al., 2007). Employing an open-field, we assessed NOR memory from P163 to P165 in adult rats (P220) following adolescent binge ethanol treatment. During the habituation phase, AIE-treated animals evidenced increased latencies to enter the center of the apparatus, relative to CONs [F(1, 13) = 6.3, p < 0.05; see Figure 6A]. There was no effect of AIE treatment on distance traveled, duration in the center, or number of entries into the center (all p > 0.08). Adolescent binge ethanol exposure did not affect any of the measures during the familiarization phase (all p > 0.1). Further, neither group of subjects evidenced an object preference during the familiarization phase of the NOR task as evidenced by no difference in the number of contacts (both p > 0.7) or time spent in contact with either object (both p > 0.1). During the testing phase, AIE treatment significantly reduced the discrimination ratio relative to CONs [F(1, 13) = 16.3, p < 0.01; see Figure 6B]. Together, these data reveal that AIE treatment leads to long-term impairments in hippocampal-dependent object recognition memory as well as increased latencies to enter the center of the maze.


Binge ethanol exposure during adolescence leads to a persistent loss of neurogenesis in the dorsal and ventral hippocampus that is associated with impaired adult cognitive functioning.

Vetreno RP, Crews FT - Front Neurosci (2015)

Adolescent intermittent ethanol (AIE) treatment leads to long-term deficits in object recognition memory. (A) Latency to enter the center of the open-field apparatus during the first trial, which provides a measure of thigmotaxis, was significantly increased in adult rats following AIE treatment. (B) Adolescent intermittent ethanol treatment significantly reduced the discrimination index, which is indicative of impaired object recognition memory, in adult rats relative to CONs. Data are presented as mean ± SEM. *indicates p < 0.05; **indicates p < 0.01, relative to CON rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325907&req=5

Figure 6: Adolescent intermittent ethanol (AIE) treatment leads to long-term deficits in object recognition memory. (A) Latency to enter the center of the open-field apparatus during the first trial, which provides a measure of thigmotaxis, was significantly increased in adult rats following AIE treatment. (B) Adolescent intermittent ethanol treatment significantly reduced the discrimination index, which is indicative of impaired object recognition memory, in adult rats relative to CONs. Data are presented as mean ± SEM. *indicates p < 0.05; **indicates p < 0.01, relative to CON rats.
Mentions: Previous studies found that adolescent binge ethanol treatment of mice reduces object recognition memory 3 weeks after ethanol treatment (Pascual et al., 2007). Employing an open-field, we assessed NOR memory from P163 to P165 in adult rats (P220) following adolescent binge ethanol treatment. During the habituation phase, AIE-treated animals evidenced increased latencies to enter the center of the apparatus, relative to CONs [F(1, 13) = 6.3, p < 0.05; see Figure 6A]. There was no effect of AIE treatment on distance traveled, duration in the center, or number of entries into the center (all p > 0.08). Adolescent binge ethanol exposure did not affect any of the measures during the familiarization phase (all p > 0.1). Further, neither group of subjects evidenced an object preference during the familiarization phase of the NOR task as evidenced by no difference in the number of contacts (both p > 0.7) or time spent in contact with either object (both p > 0.1). During the testing phase, AIE treatment significantly reduced the discrimination ratio relative to CONs [F(1, 13) = 16.3, p < 0.01; see Figure 6B]. Together, these data reveal that AIE treatment leads to long-term impairments in hippocampal-dependent object recognition memory as well as increased latencies to enter the center of the maze.

Bottom Line: This reduction in neurogenesis was accompanied by a concomitant reduction in proliferating cells (Ki-67) and an increase in cell death (cleaved caspase-3).In the hippocampus, AIE treatment induced a long-term upregulation of neuroimmune genes, including Toll-like receptor 4 (TLR4) and its endogenous agonist high-mobility group box 1 as well as several proinflammatory signaling molecules.Interestingly, object recognition memory was positively correlated with DCX + IR in both the dorsal and ventral hippocampal dentate gyrus while latency to enter the center of the apparatus was negatively correlated with DCX + IR in the ventral dentate gyrus.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina Chapel Hill, NC, USA.

ABSTRACT
Adolescence is a developmental period that coincides with the maturation of adult cognitive faculties. Binge drinking is common during adolescence and can impact brain maturation. Using a rodent model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 20% EtOH w/v; 2 days on/2 days off from postnatal day [P]25 to P55), we discovered that AIE treatment reduced neurogenesis (i.e., doublecortin-immunoreactive [DCX + IR] cells) in both the dorsal and ventral hippocampal dentate gyrus of late adolescent (P56) male Wistar rats that persisted during abstinence into adulthood (P220). This reduction in neurogenesis was accompanied by a concomitant reduction in proliferating cells (Ki-67) and an increase in cell death (cleaved caspase-3). In the hippocampus, AIE treatment induced a long-term upregulation of neuroimmune genes, including Toll-like receptor 4 (TLR4) and its endogenous agonist high-mobility group box 1 as well as several proinflammatory signaling molecules. Administration of lipopolysaccharide, a gram-negative endotoxin agonist at TLR4, to young adult rats (P70) produced a similar reduction of DCX + IR cells that was observed in AIE-treated animals. Behaviorally, AIE treatment impaired object recognition on the novel object recognition task when assessed from P163 to P165. Interestingly, object recognition memory was positively correlated with DCX + IR in both the dorsal and ventral hippocampal dentate gyrus while latency to enter the center of the apparatus was negatively correlated with DCX + IR in the ventral dentate gyrus. Together, these data reveal that adolescent binge ethanol exposure persistently inhibits neurogenesis throughout the hippocampus, possibly through neuroimmune mechanisms, which might contribute to altered adult cognitive and emotive function.

No MeSH data available.


Related in: MedlinePlus