Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells

Abstract

We previously showed that 16-day-old rats exposed to a relatively high dose of ethanol at 10-15 postnatal days of age have fewer neurons in the hilus region of the hippocampus compared with controls. Dentate gyrus granule cell numbers, however, showed no statistically significant changes attributable to the ethanol treatment. It is possible that some of the changes in brain morphology, brought about as a result of the exposure to ethanol during early life, may not be manifested until later in life. This question has been further addressed in an extension to our previous study. Wistar rats were exposed to a relatively high daily dose of ethanol on postnatal days 10-15 by placement in a chamber containing ethanol vapour, for 3 h/day. The blood ethanol concentration was found to be approximately 430 mg/dl at the end of the period of exposure. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anaesthetised and killed either at 16 or 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle and the physical disector methods were used to estimate, respectively, the regional volumes and neuron cell numerical densities in the hilus and granule cell regions of the dentate gyrus. The total numbers of neurons in the hilus region and granule cell layer were computed from these estimates. It was found that 16-day-old animals had 398,000-441,000 granule cells, irrespective of group. The numbers of granule cells increased such that by 30 days of age, rats had 487,000-525,500 granule cells. However, there were no significant differences between ethanol-treated rats and their age-matched controls in granule cell numbers. In contrast, ethanol-treated rats had slightly but significantly fewer neurons in the hilus region than did control animals at 16 days of age, but not at 30 days of age. Therefore, it appears that a short period of ethanol exposure during early life can have effects on neuron numbers of some hippocampal neurons, but not others. The effects on hilar neuron numbers, observed as a result of such short periods of ethanol treatment, appeared to be transitory.

Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

“…Similarly, vapor inhalation of ethanol during postnatal days 10–15, increases the hippocampal BDNF mRNA level in P16 and P20 rats and decreases it in P60 rats [62]. This window of ethanol exposure (postnatal days 10–15) reduces the total number of pyramidal and hilar neurons in the hippocampus [63,64,65]. In addition, early postnatal ethanol exposure (postnatal day 4–10) elevated BDNF protein level on postnatal day 10, and returned it to control levels on postnatal day 21 in the hippocampus and cortex/striatum [66].…”

Environmental Factors and Limbic Vulnerability in Childhood Autism

“…Glucocorticoid excess and X-ray irradiation, like TMT, selectively cause loss of dentate granule neurons [75,78,96] . In contrast, early ethanol exposure selectively reduces neuronal number in the dentate hilar region, and not in the granule cell layer [76] . X-irradiation and chemotherapeutic agents cause loss of both subgranular progenitor cells and nondividing dentate hilar oligodendrocytes [96][97][98] .…”

“…Agents causing specific damage to the hippocampus include bacterial toxins [65,66] , vitamin B1 deficiency [67,68] , excess homocysteine [69,70] , hepatic encephalopathy [71] ; copper deficiency [72] , glucocorticoid excess or deficiency [73][74][75] , ethanol exposure [76] , oxygen deprivation [52,77] and irradiation [78] . Limbic damage, particularly in the hippocampus, is the primary outcome of challenge, while other brain regions often largely retain their integrity.…”

Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats

“…We have focused on the period subsequent to the BGS, i.e., PND10-15. In fact, we previously reported that early postnatal maternal separation during PND10-15 causes an abnormal, age-dependent change in BDNF mRNA expression that is accompanied by unchanged neuronal numbers in the rat hippocampus (Kuma et al, 2004;Miki et al, 2000Miki et al, , 2003Miki et al, , 2004Miki et al, , 2008. These studies strongly imply the importance of examining the process at the molecular level, and investigating possible molecular processes caused by maternal separation after the BGS that may be involved in other brain regions.…”