Activity‐based anorexia during adolescence disrupts normal development of the CA1 pyramidal cells in the ventral hippocampus of female rats

Abstract

Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and irrational fears of gaining weight. There is no accepted pharmacological treatment for AN, and AN has the highest mortality rate among psychiatric illnesses. Anorexia nervosa most commonly affects females during adolescence, suggesting an effect of sex and hormones on vulnerability to the disease. Activity-based anorexia (ABA) is a rodent model of AN that shares symptoms with AN, including over-exercise, elevation of stress hormones, and genetic links to anxiety traits. We previously reported that ABA in adolescent female rats results in increased apical dendritic branching in CA1 pyramidal cells of the ventral hippocampus at postnatal day 44 (P44). To examine the long-term effects of adolescent ABA (P44) in female rats, we compared the apical branching in the ventral hippocampal CA1 after recovery from ABA (P51) and after a relapse of ABA (P55) with age-matched controls. To examine the age-dependence of the hippocampal plasticity, we examined the effect of ABA during adulthood (P67). We found that while ABA at P44 resulted in increased branching of ventral hippocampal pyramidal cells, relapse of ABA at P55 resulted in decreased branching. Activity-based anorexia induced during adulthood did not have an effect on dendritic branching, suggesting an age-dependence of the vulnerability to structural plasticity. Cells from control animals were found to exhibit a dramatic increase in branching, more than doubling from P44 to P51, followed by pruning from P51 to P55. The proportion of mature spines on dendrites from the P44-ABA animals is similar to that on dendrites from P55-CON animals. These results suggest that the experience of ABA may cause precocious anatomical development of the ventral hippocampus. Importantly, we found that adolescence is a period of continued development of the hippocampus, and increased vulnerability to mental disorders during adolescence may be due to insults during this developmentally critical period.

Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa

“…In accordance with this view, we observed a tight correlation between the animals’ performance in spatial learning and their food anticipatory activity 10 days earlier, measured by the increase in wheel running during the 6 hours preceding the hour of food access (Chowdhury et al, 2014d). …”

“…In the ventral hippocampus, dendritic lengths in SR are increased by 70%, contributing to the increased branching in SR by 44%, again with no change in spine density, indicating a substantial increase of excitatory synapses formed between CA3 afferents to CA1 pyramidal cells. The effect of ABA appears to be to induce precocious maturation of the apical dendrites in the ventral hippocampus, since the dendritic exuberance observed at P44 by the ABA animals is similar to the pattern observed a week later in the ventral hippocampus of control animals that are never exposed to FR or a wheel (Chowdhury et al, 2014c). This interpretation is supported by data on spine morphology: more of the spines of the P44-ABA animals appear mature (mushroom and stubby spines, rather than filopodia), compared to those of age-matched controls (P44-CON) but are similar to the proportion observed a week later in the hippocampus of controls (P51-CON) (Chowdhury et al, 2014d).…”

“…2). This is paralleled by a 50% increase in the proportion of dendritic spines in stratum radiatum (SR) that are mature (mushroom and stubby spines) (Chowdhury et al, 2014c) (Fig. 2).…”

“…This is based on our observation that 7 days of recovery from ABA (P51 ABA recov in Fig. 4) is sufficiently long to eliminate the anatomical differences between the ABA and CON (Chowdhury et al, 2014d). It is likely that adolescent hippocampal neurons exhibit greater plasticity than adults’, and this allows for normalization of ABA-induced changes.…”

“…Moreover, severe weight loss that is associated with FR, whether with or without wheel access, do not cause irreversible atrophy of hippocampal neurons. These are part of the data that appear in publications (Chowdhury et al, 2014a; Chowdhury et al, 2014d). This figure was modified from a figure of a book chapter (Aoki and Erisir, 2014).…”