Neonatal alcohol exposure disrupts hippocampal neurogenesis and contextual fear conditioning in adult rats

Abstract

Developmental alcohol exposure can permanently alter brain structures and produce functional impairments in many aspects of behavior, including learning and memory. This study evaluates the effect of neonatal alcohol exposure on adult neurogenesis in the dentate gyrus of the hippocampus and the implications of such exposure for hippocampus-dependent contextual fear conditioning. Alcohol-exposed rats (AE) received 5.25 g/kg/day of alcohol on postnatal days (PD) 4-9 (third trimester in humans), in a binge-like manner. Two control groups were included: sham-intubated (SI) and suckle-control (SC). Animals were housed in social cages (3/cage) after weaning. On PD80, animals were injected with 200 mg/kg BrdU. Half of the animals were sacrificed two hours later. The remainder were sacrificed on PD114 to evaluate cell survival; separate AE, SI, and SC rats not injected with BrdU were tested for the context preexposure facilitation effect (CPFE; ∼PD117). There was no difference in the number of BrdU+ cells in AE, SI and SC groups on PD80. On PD114, cell survival was significantly decreased in AE rats, demonstrating that developmental alcohol exposure damages new cells' ability to incorporate into the network and survive. Behaviorally tested SC and SI groups preexposed to the training context 24h prior to receiving a 1.5mA 2s footshock froze significantly more during the context test than their counterparts preexposed to an alternate context. AE rats failed to show the CPFE. The current study shows the detrimental, long-lasting effects of developmental alcohol exposure on hippocampal adult neurogenesis and contextual fear conditioning.

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

“…Altered hippocampal neurogenesis has been associated with a number of neuropsychiatric diseases [58,59], hippocampus-dependent behavioral deficits, and neurodegenerative disorders [60][61][62][63][64]. In the environment, diverse toxic chemicals, such as heavy metals, solvents, pesticides, and EDCs, that can modulate the hippocampal neurogenesis are present [10][11][12][13][14][15]. BPA is one of the toxic environmental and industrial EDCs, targets several tissues and organs, and causes hepatoxicity, immunotoxicity, genotoxicity, neurotoxicity, and mutagenic and carcinogenic effects [65].…”

“…Several environmental toxicants including heavy metals, solvents, pesticides, and endocrine-disrupting chemicals (EDCs) modulate the normal neurodevelopmental processes both during fetal and adult stages and cause cognitive dysfunction [10][11][12][13][14][15]. Bisphenol A (BPA), is an endocrinedisrupting synthetic xenoestrogen, widely distributed in the environment, and used for the production of number of polycarbonate plastics and epoxy resin-containing consumer products [16,17].…”

Variants of contextual fear conditioning induce differential patterns of Egr-1 activity within the young adult prefrontal cortex

“…Prior to experimentation, all animals were transported to a holding room in the behavioral lab and handled for five minutes a day for five consecutive days by the same experimenter, similar to Malkani, et al (2004) and Hamilton et al (2011) [15, 38]. …”

“…The general training procedure used was similar to Murawski & Stanton (2010) and Hamilton et al (2011) [38, 39]. Two experimental conditions were run over three consecutive days in the CPFE paradigm).…”

Using the context preexposure facilitation effect to study long-term context memory in preweanling, juvenile, adolescent, and adult rats

“…To test this hypothesis, Experiment 2 assessed retention of context memory in adult rats at 24 h versus the 22-day interval that yielded forgetting in juvenile rats. The CPFE procedure used in this experiment was similar to that used in Experiment 1 and in other studies of adult rats from this laboratory [19]. …”