Activity-Based Anorexia Alters the Expression of BDNF Transcripts in the Mesocorticolimbic Reward Circuit

Abstract

Anorexia nervosa (AN) is a complex eating disorder with severe dysregulation of appetitive behavior. The activity-based anorexia (ABA) paradigm is an animal model in which rodents exposed to both running wheels and scheduled feeding develop aspects of AN including paradoxical hypophagia, dramatic weight loss, and hyperactivity, while animals exposed to only one condition maintain normal body weight. Brain-derived neurotrophic factor (BDNF), an activity-dependent modulator of neuronal plasticity, is reduced in the serum of AN patients, and is a known regulator of feeding and weight maintenance. We assessed the effects of scheduled feeding, running wheel access, or both on the expression of BDNF transcripts within the mesocorticolimbic pathway. We also assessed the expression of neuronal cell adhesion molecule 1 (NCAM1) to explore the specificity of effects on BDNF within the mesocorticolimbic pathway. Scheduled feeding increased the levels of both transcripts in the hippocampus (HPC), increased NCAM1 mRNA expression in the ventral tegmental area (VTA), and decreased BDNF mRNA levels in the medial prefrontal cortex (mPFC). In addition, wheel running increased BDNF mRNA expression in the VTA. No changes in either transcript were observed in the nucleus accumbens (NAc). Furthermore, no changes in either transcript were induced by the combined scheduled feeding and wheel access condition. These data indicate that scheduled feeding or wheel running alter BDNF and NCAM1 expression levels in specific regions of the mesocorticolimbic pathway. These findings contribute to our current knowledge of the molecular alterations induced by ABA and may help elucidate possible mechanisms of AN pathology.

Activity Based Anorexia as an Animal Model for Anorexia Nervosa–A Systematic Review

“…The hippocampus is responsible for transmitting memory content from short to long-term memory (167). Restricted feeding for 14 days increased the transcripts of the growth factor BDNF in the hippocampus of Balb/cJ female mice (67), suggesting a putative role of the hippocampus in ABA. In contrast, female A/J inbred mice undergoing the standard ABA protocol showed decreased BDNF expression in the hippocampus (59).…”

“…Restricted food access elevated mRNA expression levels of neuronal cell adhesion molecule 1 (NCAM1), involved in the formation and modulation of synaptic contacts in the VTA of Balb/cJ female mice (67). Wheel running alone elevated mRNA expression of the growth factor, brain-derived neutrotrophic (BDNF) in the VTA.…”

“…Wheel running alone elevated mRNA expression of the growth factor, brain-derived neutrotrophic (BDNF) in the VTA. When both conditions were combined, no effects on BDNF or NCAM1 mRNA expression within the mesocorticolimbic pathway could be observed (67). Female A/J inbred mice with typical signs of ABA showed elevated dopamine D 2 receptor expression in the caudate putamen (59).…”

Rola neurotroficznego czynnika pochodzenia mózgowego w kontroli łaknienia

“…Badania na modelach zwierzęcych, u których eksperymentalnie wywołano AN, wykazały, że zarówno ograniczenia żywieniowe jak i aktywność fizyczna (a jednym z komponentów obrazu chorych na AN jest wzmożona aktywność fizyczna) powodują zmiany ekspresji mRNA BDNF w strukturach mezokortykolimbicznych [80], co sugerowałoby, że ta neurotrofina uczestniczy w szlaku układu nagrody i hedonistycznym poborze pokarmu. Z kolei w otyłości zaobserwowano, że zarówno nieprawidłowości w samej cząsteczce BDNF jak i mutacje w obrębie receptora TrkB są powiązane z przyrostem masy ciała i otyłością [81,82].…”

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

“…Gene-wise analysis with MAGMA prioritized 79 Bonferroni-significant genes, most within the multigenic locus on chr3 (Supplementary Table 11). MAGMA indicated an association with NCAM1 (Supplementary Table 11) the expression of which increases in response to food restriction in a rodent activity-based anorexia nervosa model 25 . Partitioned heritability analysis showed, as with other GWAS 26 , considerable enrichment of SNP-h 2 in conserved regions (fold enrichment = 24.97, s.e.…”