Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

Abstract

Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65–70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume. © 2015 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 57:470–485, 2015.

Prenatal Alcohol Exposure Affects Progenitor Cell Numbers in Olfactory Bulbs and Dentate Gyrus of Vervet Monkeys

“…Protocols for the development of FAE and sucrose control offspring have been previously described in some detail [32]. Briefly, alcohol-preferring adult females were identified and housed in small breeding groups with a same age alcohol-avoiding male.…”

“…These were then cryoprotected in 30% buffered sucrose for 48 h at 4 °C, frozen in isopentane at −65 °C and stored at −80 °C until further processing. Brain tissue underwent graded sucrose cryoprotection (10%, 20% and 30%) over the course of 7 days prior to freezing in isopentane at −65 °C [31,32]. …”

“…Affected individuals often exhibit deficits in executive function [21,22], cognition [23] and attention [16,24,25,26,27,28]. Evidence from clinical and animal model studies suggests that the fronto-limbic system is acutely affected by FAE [29,30,31,32,33]. Within this context, the hippocampus is particularly vulnerable.…”

“…Clinical imaging studies report reduction in hippocampal volume in FASD [34,35], and rodent studies have defined the third trimester equivalent as a critical period for ethanol-induced hippocampal neuron loss [36,37]. Our own data from a naturalistic non-human primate model of FAE demonstrate that, in addition to a 35% neuronal reduction of frontal cortex neurons [31], there is significant and pervasive loss of hippocampal volume and neuronal populations following moderate and voluntary maternal alcohol consumption during the third trimester [32]. …”

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

“…132,133,137,140,161 Although the immature neuronal population is susceptible to perinatal HIV-1 infection, it may also be the key to therapeutic intervention aimed at reducing the impact of HIV-1 induced neurological impairment. 39,104,121,192 The extent of HIV-1 infection of specific cell types, neuronal loss, and its relationship to viral loads, and the CNS as a potential reservoir for latent HIV-1 in infants is currently unknown. This limits the ability to develop and evaluate therapeutic paradigms to minimize the neurological impairments as a result of HIV-1 infection.…”