RESUMEN
In neonatal brain development there is a period of normal apoptotic cell death that regulates adult neuron number. At approximately the same period, ethanol exposure can cause a dramatic spike in apoptotic cell death. While ethanol-induced apoptosis has been shown to reduce adult neuron number, questions remain about the regional selectivity of the ethanol effect, and whether the brain might have some capacity to overcome the initial neuron loss. The present study used stereological cell counting to compare cumulative neuron loss 8 h after postnatal day 7 (P7) ethanol treatment to that of animals left to mature to adulthood (P70). Across several brain regions we found that the reduction of total neuron number after 8 h was as large as that of adult animals. Comparison between regions revealed that some areas are more vulnerable, with neuron loss in the anterior thalamic nuclei > the medial septum/vertical diagonal band, dorsal subiculum, and dorsal lateral geniculate nucleus > the mammillary bodies and cingulate cortex > whole neocortex. In contrast to estimates of total neuron number, estimates of apoptotic cell number in Nissl-stained sections at 8 h after ethanol treatment provided a less reliable predictor of adult neuron loss. The findings show that ethanol-induced neonatal apoptosis often causes immediate neuron deficits that persist in adulthood, and furthermore suggests that the brain may have limited capacity to compensate for ethanol-induced neuron loss.
RESUMEN
BACKGROUND: An understudied variant of Alzheimer's disease (AD), the behavioral/dysexecutive variant of AD (bvAD), is associated with progressive personality, behavior, and/or executive dysfunction and frontal atrophy. OBJECTIVE: This study characterizes the neuropsychological and neuroanatomical features associated with bvAD by comparing it to behavioral variant frontotemporal dementia (bvFTD), amnestic AD (aAD), and subjects with normal cognition. METHODS: Subjects included 16 bvAD, 67 bvFTD, 18 aAD patients, and 26 healthy controls. Neuropsychological assessment and MRI data were compared between these groups. RESULTS: Compared to bvFTD, bvAD showed more significant visuospatial impairments (Rey Figure copy and recall), more irritability (Neuropsychological Inventory), and equivalent verbal memory (Philadelphia Verbal Learning Test). Compared to aAD, bvAD indicated more executive dysfunction (F-letter fluency) and better visuospatial performance. Neuroimaging analysis found that bvAD showed cortical thinning relative to bvFTD posteriorly in left temporal-occipital regions; bvFTD had cortical thinning relative to bvAD in left inferior frontal cortex. bvAD had cortical thinning relative to aAD in prefrontal and anterior temporal regions. All patient groups had lower volumes than controls in both anterior and posterior hippocampus. However, bvAD patients had higher average volume than aAD patients in posterior hippocampus and higher volume than bvFTD patients in anterior hippocampus after adjustment for age and intracranial volume. CONCLUSION: Findings demonstrated that underlying pathology mediates disease presentation in bvAD and bvFTD.
