Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence

Persistent Loss of Hippocampal Neurogenesis and Increased Cell Death following Adolescent, but Not Adult, Chronic Ethanol Exposure

Although adolescence is a common age to initiate alcohol consumption, long-lasting consequences of exposure to alcohol at this time of considerable brain maturation are largely unknown. In studies utilizing rodents, behavioral evidence is beginning to emerge suggesting that the hippocampus may be persistently affected by repeated ethanol exposure during adolescence, but not by comparable alcohol exposure in adulthood. The purpose of this series of experiments was to explore a potential mechanism of hippocampal dysfunction in adults exposed to ethanol during adolescence. Given that disruption in adult neurogenesis has been reported to impair performance on tasks thought to be hippocampally-related, we used immunohistochemistry to assess levels of doublecortin (DCX), an endogenous marker of immature neurons, in the dentate gyrus (DG) of the hippocampus 3–4 weeks after adolescent (P28–48) or adult (P70–90) intermittent ethanol exposure to 4 g/kg ethanol administered intragastrically. We also investigated another neurogenic niche, the subventricular zone (SVZ), to determine if effects of ethanol exposure were region-specific. Levels of cell proliferation and cell death were also examined in the DG via assessing Ki67 and cleaved caspase-3 immunoreactivity, respectively. Significantly less DCX was observed in the DG of adolescent (but not adult) ethanol exposed animals ~4 weeks post-exposure when these animals were compared to control age-mates. Effects of adolescent ethanol on DCX immunoreactivity were specific to the hippocampus, with no significant exposure effects emerging in the SVZ. In both DG and SVZ there was a significant age-related decline in neurogenesis as indexed by DCX. The persistent effect of adolescent ethanol exposure on reduced DCX in the DG appears to be related to significant increases in cell death, with significantly more cleaved caspase-3 positive immunoreactivity observed in the adolescent ethanol group compared to controls, but no alterations in cell proliferation when indexed by Ki67. These results suggest that a history of adolescent ethanol exposure results in lowered levels of differentiating neurons, likely due at least in part to increased cell death of immature neurons. These effects were evident in adulthood, weeks following termination of the chronic exposure, and may contribute to previously reported behavioral deficits on hippocampal-related tasks after the chronic exposure

Persistent Loss of Hippocampal Neurogenesis and Increased Cell Death following Adolescent, but Not Adult, Chronic Ethanol Exposure

Although adolescence is a common age to initiate alcohol consumption, long-lasting consequences of exposure to alcohol at this time of considerable brain maturation are largely unknown. In studies utilizing rodents, behavioral evidence is beginning to emerge suggesting that the hippocampus may be persistently affected by repeated ethanol exposure during adolescence, but not by comparable alcohol exposure in adulthood. The purpose of this series of experiments was to explore a potential mechanism of hippocampal dysfunction in adults exposed to ethanol during adolescence. Given that disruption in adult neurogenesis has been reported to impair performance on tasks thought to be hippocampally-related, we used immunohistochemistry to assess levels of doublecortin (DCX), an endogenous marker of immature neurons, in the dentate gyrus (DG) of the hippocampus 3–4 weeks after adolescent (P28–48) or adult (P70–90) intermittent ethanol exposure to 4 g/kg ethanol administered intragastrically. We also investigated another neurogenic niche, the subventricular zone (SVZ), to determine if effects of ethanol exposure were region-specific. Levels of cell proliferation and cell death were also examined in the DG via assessing Ki67 and cleaved caspase-3 immunoreactivity, respectively. Significantly less DCX was observed in the DG of adolescent (but not adult) ethanol exposed animals ~4 weeks post-exposure when these animals were compared to control age-mates. Effects of adolescent ethanol on DCX immunoreactivity were specific to the hippocampus, with no significant exposure effects emerging in the SVZ. In both DG and SVZ there was a significant age-related decline in neurogenesis as indexed by DCX. The persistent effect of adolescent ethanol exposure on reduced DCX in the DG appears to be related to significant increases in cell death, with significantly more cleaved caspase-3 positive immunoreactivity observed in the adolescent ethanol group compared to controls, but no alterations in cell proliferation when indexed by Ki67. These results suggest that a history of adolescent ethanol exposure results in lowered levels of differentiating neurons, likely due at least in part to increased cell death of immature neurons. These effects were evident in adulthood, weeks following termination of the chronic exposure, and may contribute to previously reported behavioral deficits on hippocampal-related tasks after the chronic exposure

Southern right whale (\u3ci\u3eEubalaena australis\u3c/i\u3e) calf mortality at Península Valdés, Argentina: Are harmful algal blooms to blame?

Península Valdés (PV) in Argentina is an important calving ground for southern right whales (SRWs, Eubalaena australis). Since 2005, right whale mortality has increased at PV, with most of the deaths (~90%) being calves \u3c3mo old. We investigated the potential involvement of harmful algal blooms (HABs) in these deaths by examining data that include: timing of the SRW deaths, biotoxins in samples from dead SRWs, abundances of the diatom, Pseudo-nitzschia spp., and the dinoflagellate, Alexandrium tamarense, shellfish harvesting closure dates, seasonal availability of whale prey at PV and satellite chlorophyll data. Evidence of the whales’ exposure to HAB toxins includes trace levels of paralytic shellfish toxins (PSTs) and domoic acid (DA) in tissues of some dead whales, and fragments of Pseudo-nitzschia spp. frustules in whale feces. Additionally, whales are present at PV during both closures of the shellfish industry (due to high levels of PSTs) and periods with high levels of Pseudo-nitzschia spp. and A. tamarense. There is a positive statistical relationship between monthly Pseudo-nitzschia densities (but not A. tamarense) and calf deaths in both gulfs of PV

Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence

Southern right whale (Eubalaena australis) calf mortality at Península Valdés, Argentina: Are harmful algal blooms to blame?

Península Valdés (PV) in Argentina is an important calving ground for southern right whales (SRWs, Eubalaena australis). Since 2005, right whale mortality has increased at PV, with most of the deaths (~90%) being calves <3 mo old. We investigated the potential involvement of harmful algal blooms (HABs) in these deaths by examining data that include: timing of the SRW deaths, biotoxins in samples from dead SRWs, abundances of the diatom, Pseudo-nitzschia spp., and the dinoflagellate, Alexandrium tamarense, shellfish harvesting closure dates, seasonal availability of whale prey at PV and satellite chlorophyll data. Evidence of the whales' exposure to HAB toxins includes trace levels of paralytic shellfish toxins (PSTs) and domoic acid (DA) in tissues of some dead whales, and fragments of Pseudo-nitzschia spp. frustules in whale feces. Additionally, whales are present at PV during both closures of the shellfish industry (due to high levels of PSTs) and periods with high levels of Pseudo-nitzschia spp. and A. tamarense. There is a positive statistical relationship between monthly Pseudo-nitzschia densities (but not A. tamarense) and calf deaths in both gulfs of PV.Fil: Wilson, Cara. University Of Utah; Estados UnidosFil: Sastre, A. Viviana. Universidad Nacional de la Patagonia; ArgentinaFil: Hoffmeyer, Monica Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto Argentino de Oceanografía (i); Argentina. Universidad Tecnológica Nacional. Facultad Regional Bahía Blanca; ArgentinaFil: Rowntree, Victoria J.. Southern Right Whale Health Monitoring Program; Argentina. University of Utah; Estados UnidosFil: Fire, Spencer E.. Center for Coastal Environmental Health and Biomolecular Research; Estados UnidosFil: Santinelli, Norma H.. Universidad Nacional de la Patagonia; ArgentinaFil: Díaz Ovejero, Soledad. Universidad Nacional de la Patagonia; ArgentinaFil: D'agostino, Valeria Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Marón, Carina F.. Southern Right Whale Health Monitoring Program; Argentina. University of Utah; Estados UnidosFil: Doucette, Gregory J.. Center for Coastal Environmental Health and Biomolecular Research; Estados UnidosFil: Broadwater, Margaret H. . Center for Coastal Environmental Health and Biomolecular Research; Estados UnidosFil: Wang, Zhihong . Center for Coastal Environmental Health and Biomolecular Research; Estados UnidosFil: Montoya, Nora. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Seger, Jon. University of Utah; Estados UnidosFil: Adler, Frederick R.. University of Utah; Estados UnidosFil: Sironi, Mariano. Southern Right Whale Health Monitoring Program; Argentina. Instituto de Conservación de Ballenas; ArgentinaFil: Uhart, Marcela M.. Southern Right Whale Health Monitoring Program; Argentina. University of California; Estados Unido