No abstract

Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. Male C57BL/6J mice received either saline or 5 g/kg ethanol (two doses, two hours apart) on PD5, 7, and 9. On PD35, animals received a running wheel or remained sedentary for 48 days before behavioral testing and perfusion on PD83. The number of PV+ interneurons was stereologically measured in three separate mPFC subregions: infralimbic, prelimbic and anterior cingulate cortices (ACC). Neonatal alcohol exposure decreased number of PV+ interneurons and volume of the ACC, but the other regions of the mPFC were spared. Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.

Prenatal alcohol exposure can produce permanent alterations in brain structure and profound behavioral deficits. Mouse models can help discover mechanisms and identify potentially useful interventions. This study examined long-term influences of either a single or repeated alcohol exposure during the third-trimester equivalent on survival of new neurons in the hippocampus, behavioral performance on the Passive avoidance and Rotarod tasks, and the potential role of exercise as a therapeutic intervention. C57BL/6J male mice received either saline or 5 g/kg ethanol split into two s.c. injections, two hours apart, on postnatal day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned on PD21 and received either a running wheel or remained sedentary from PD35-PD80/81. From PD36-45, mice received i.p. injections of 50 mg/kg bromodeoxyuridine (BrdU) to label dividing cells. Behavioral testing occurred between PD72-79. Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) were measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in either experiment. Running significantly increased number of BrdU+ and DCX+ cells in both treatment groups. Alcohol-induced deficits on Rotarod performance and acquisition of the Passive avoidance task (Day 1) were evident only in Experiment 2 and running rescued these deficits. These data suggest neonatal alcohol exposure does not result in long-term impairments in adult hippocampal neurogenesis in the mouse model. Three doses of ethanol were necessary to induce behavioral deficits. Finally, the mechanisms by which exercise ameliorated the neonatal alcohol induced behavioral deficits remain unknown.

No abstract

In laboratory time-based prospective memory tasks, older adults typically perform worse than younger adults do. It has been suggested that less frequent clock checking due to problems with executive functions may be responsible. We aimed to investigate the role of clock checking in older adults’ time-based prospective memory and to clarify whether executive functions would be associated with clock checking and consequently, with time-based prospective memory. We included 62 healthy older adults (62-85 years of age) and applied tasks of time-based prospective memory as well as of executive functions (i.e., inhibition, fluency, and working memory). We used mediation analysis to test whether time-based prospective memory declined with advancing age due to less frequent clock checking. In addition, we tested whether there would be an association between executive functions and clock checking or time-based prospective memory. Time-based prospective memory declined with advancing age due to less frequent clock checking within 30s prior to intention completion. We only found a link between executive functions and clock checking (or time-based prospective memory) when not controlling for age. Our results support the importance of clock checking for time-based prospective memory and add to the current literature that older adults’ prospective memory declines because they are less able to adapt their clock checking. Yet, the reason why older adults are less able to adapt their clock checking still remains open. Our results do not indicate that executive function deficits play a central role.