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Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

Swartzwelder HS, Acheson SK, Miller KM, Sexton HG, Liu W, Crews FT, Risher ML - PLoS ONE (2015)

Bottom Line: Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive.AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4.Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

View Article: PubMed Central - PubMed

Affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychology and Neuroscience, Duke University Medical Center Durham, Durham, North Carolina, 27705, United States of America.

ABSTRACT
The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

No MeSH data available.


Related in: MedlinePlus

AIE decreases ChAT+IR in the basal forebrain in adulthood.AIE decreases ChAT+IR in the Ch1 and Ch2 nuclei of the basal forebrain of adult rats (a). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch1 and Ch2 nuclei at 0.70 ~ 0.20 mm from bregma 25 days after AIE, **p<0.01. Right Panel—representative photomicrography ChAT+IR neurons in the Ch1 and Ch2 nuclei from a control animal (Control), and an AIE-exposed animal (ETOH). AIE decreases ChAT+IR in the Ch3 and Ch4 nuclei of the basal forebrain of adult rats (b). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch3 and Ch4 nuclei at 0.48 ~ 0.40 mm from bregma 25 days after AIE, *p = 0.046. Right Panel—representative photomicrography ChAT+IR neurons in the Ch3 and Ch4 nuclei from a control animal (Control), and an ethanol-exposed animal (ETOH). Scale bar = 50 μm.
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pone.0140042.g003: AIE decreases ChAT+IR in the basal forebrain in adulthood.AIE decreases ChAT+IR in the Ch1 and Ch2 nuclei of the basal forebrain of adult rats (a). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch1 and Ch2 nuclei at 0.70 ~ 0.20 mm from bregma 25 days after AIE, **p<0.01. Right Panel—representative photomicrography ChAT+IR neurons in the Ch1 and Ch2 nuclei from a control animal (Control), and an AIE-exposed animal (ETOH). AIE decreases ChAT+IR in the Ch3 and Ch4 nuclei of the basal forebrain of adult rats (b). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch3 and Ch4 nuclei at 0.48 ~ 0.40 mm from bregma 25 days after AIE, *p = 0.046. Right Panel—representative photomicrography ChAT+IR neurons in the Ch3 and Ch4 nuclei from a control animal (Control), and an ethanol-exposed animal (ETOH). Scale bar = 50 μm.

Mentions: As Fig 2 illustrates, AIE decreased ChAT+IR in the medial septum and vertical limb of the diagonal band of Broca (Ch1 and Ch2) nuclei of the basal forebrain of adult rats 25 days after the termination of AIE. Specifically, ChAT+IR cell density was decreased by approximately 50% (p<0.01) in cholinergic Ch1 and Ch2 nuclei. This is illustrated quantitatively in the left panel of Fig 2, with visualization of ChAT+IR neurons in the right panel. We also assessed diagonal band/nucleus basalis (Ch3-4) ChAT+IR neurons and found 220±26 (SEM) and 161±17 (SEM) ChAT+IR neurons/mm2 control and AIE animals, respectively (p = 0.046; Fig 3). These findings indicate AIE leads to a persistent loss of adult ChAT+ neurons, consistent with previous studies [19,20].


Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

Swartzwelder HS, Acheson SK, Miller KM, Sexton HG, Liu W, Crews FT, Risher ML - PLoS ONE (2015)

AIE decreases ChAT+IR in the basal forebrain in adulthood.AIE decreases ChAT+IR in the Ch1 and Ch2 nuclei of the basal forebrain of adult rats (a). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch1 and Ch2 nuclei at 0.70 ~ 0.20 mm from bregma 25 days after AIE, **p<0.01. Right Panel—representative photomicrography ChAT+IR neurons in the Ch1 and Ch2 nuclei from a control animal (Control), and an AIE-exposed animal (ETOH). AIE decreases ChAT+IR in the Ch3 and Ch4 nuclei of the basal forebrain of adult rats (b). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch3 and Ch4 nuclei at 0.48 ~ 0.40 mm from bregma 25 days after AIE, *p = 0.046. Right Panel—representative photomicrography ChAT+IR neurons in the Ch3 and Ch4 nuclei from a control animal (Control), and an ethanol-exposed animal (ETOH). Scale bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4631346&req=5

pone.0140042.g003: AIE decreases ChAT+IR in the basal forebrain in adulthood.AIE decreases ChAT+IR in the Ch1 and Ch2 nuclei of the basal forebrain of adult rats (a). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch1 and Ch2 nuclei at 0.70 ~ 0.20 mm from bregma 25 days after AIE, **p<0.01. Right Panel—representative photomicrography ChAT+IR neurons in the Ch1 and Ch2 nuclei from a control animal (Control), and an AIE-exposed animal (ETOH). AIE decreases ChAT+IR in the Ch3 and Ch4 nuclei of the basal forebrain of adult rats (b). Left Panel—the cell density of ChAT+IR is significantly decreased in the Ch3 and Ch4 nuclei at 0.48 ~ 0.40 mm from bregma 25 days after AIE, *p = 0.046. Right Panel—representative photomicrography ChAT+IR neurons in the Ch3 and Ch4 nuclei from a control animal (Control), and an ethanol-exposed animal (ETOH). Scale bar = 50 μm.
Mentions: As Fig 2 illustrates, AIE decreased ChAT+IR in the medial septum and vertical limb of the diagonal band of Broca (Ch1 and Ch2) nuclei of the basal forebrain of adult rats 25 days after the termination of AIE. Specifically, ChAT+IR cell density was decreased by approximately 50% (p<0.01) in cholinergic Ch1 and Ch2 nuclei. This is illustrated quantitatively in the left panel of Fig 2, with visualization of ChAT+IR neurons in the right panel. We also assessed diagonal band/nucleus basalis (Ch3-4) ChAT+IR neurons and found 220±26 (SEM) and 161±17 (SEM) ChAT+IR neurons/mm2 control and AIE animals, respectively (p = 0.046; Fig 3). These findings indicate AIE leads to a persistent loss of adult ChAT+ neurons, consistent with previous studies [19,20].

Bottom Line: Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive.AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4.Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

View Article: PubMed Central - PubMed

Affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychology and Neuroscience, Duke University Medical Center Durham, Durham, North Carolina, 27705, United States of America.

ABSTRACT
The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

No MeSH data available.


Related in: MedlinePlus