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

Abstract

Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation.

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure

“…In concordance with their previous results, a significant reduction in progenitor cell numbers was found neonatally in the animals exposed to alcohol. As expected, the progenitor cell numbers were much reduced at an age of 2 years and, furthermore, the numbers did not differ between monkeys exposed and not exposed to prenatal alcohol, demonstrating the specific vulnerability of prenatal or early age exposure to alcohol …”

“…As expected, the progenitor cell numbers were much reduced at an age of 2 years and, furthermore, the numbers did not differ between monkeys exposed and not exposed to prenatal alcohol, demonstrating the specific vulnerability of prenatal or early age exposure to alcohol. 91 Another non-human primate species displaying voluntary consumption of alcohol is the Macaca Mulatta, also called rhesus monkey. In a number of studies of rhesus monkeys, it has been shown that this species show many similarities with humans on alcohol exposure, both with regard to structure and function of the adult brain serotonin and dopamine systems, as well as behaviour.…”

Episodic Prenatal Exposure To Ethanol Affects Postnatal Neurogenesis In The Macaque Dentate Gyrus And Visual Recognition Memory

“…The primate CNS is exquisitely vulnerable to ethanol toxicity during gestational development. Prenatal exposure to ethanol causes changes in behavior (e.g., Clarren et al, 1992; Schneider et al, 2001a, 2001b, 2008, 2013; Zangenehpour et al, 2014) and brain structure (e.g., Miller et al, 1999; Mooney and Miller, 2001, 2007; Miller, 2007; Burke et al, 2019). Two factors define the neural response: the duration and the timing of ethanol exposure.…”

Introductory Chapter: Primates - What the Monkey Brain Tells the Human Brain

“…With the voluntary and naturalistic drinking pattern exhibited by vervets, we are able to address vulnerability factors, both genetic and neurochemical, leading to alcohol use and misuse [2]. We have been able to now further take advantage of the drinking patterns to examine the short-and long-term effects of prenatal ethanol exposure on the developing brain in a systematic manner which cannot be done in a clinical setting [3,[8][9][10].…”

“…Given the neurodevelopmental and homologous brain areas, the nonhuman primate offers a high degree of homological validity for the study of human development [3,8,9,11,[20][21][22][23][24]. Pathogenic validity, which addresses the disease process, in this case, depends on the question.…”