Prolonged Consumption of Sucrose in a Binge-Like Manner, Alters the Morphology of Medium Spiny Neurons in the Nucleus Accumbens Shell

Abstract

The modern diet has become highly sweetened, resulting in unprecedented levels of sugar consumption, particularly among adolescents. While chronic long-term sugar intake is known to contribute to the development of metabolic disorders including obesity and type II diabetes, little is known regarding the direct consequences of long-term, binge-like sugar consumption on the brain. Because sugar can cause the release of dopamine in the nucleus accumbens (NAc) similarly to drugs of abuse, we investigated changes in the morphology of neurons in this brain region following short- (4 weeks) and long-term (12 weeks) binge-like sucrose consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox staining to impregnate medium spiny neurons (MSNs) from the NAc core and shell of short- and long-term sucrose consuming rats and compared these to age-matched water controls. We show that prolonged binge-like sucrose consumption significantly decreased the total dendritic length of NAc shell MSNs compared to age-matched control rats. We also found that the restructuring of these neurons resulted primarily from reduced distal dendritic complexity. Conversely, we observed increased spine densities at the distal branch orders of NAc shell MSNs from long-term sucrose consuming rats. Combined, these results highlight the neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN morphology.

Keywords: binge-like consumption; long-term; medium spiny neuron; nucleus accumbens; sucrose.

Figure 1

Map showing locations of medium spiny neurons sampled from the nucleus accumbens core and shell of 4 and 12 week sucrose consuming rats and age-matched controls. Top two panels show locations of neurons sampled from the nucleus accumbens core and shell of 4 week control (triangles) and sucrose (circles) animals. Bottom two panels show positions of neurons sampled from 12 week control (triangles) and sucrose (circles) animals.

Figure 2

Decreased dendritic arbor length and increased distal dendritic spine density of medium spiny neurons (MSNs) from the nucleus accumbens (NAc) shell of long-term sucrose treated rats compared to control rats. (A,B) show representations of control (top) and long-term (12 week) sucrose (bottom) treated brightfield z-stack mosaics of Golgi-impregnated MSNs from the NAc shell (63x magnification). Inset of (A,B) shows control and long-term sucrose treated brightfield images of Golgi-impregnated MSN dendrites and dendritic spines from the NAc shell (100x magnification). (C) shows the anatomical regions that MSNs were sampled from in this study. (D) shows a scatter-plot of decreased total MSN dendritic arbor (mean ± SEM) from the NAc shell in long-term sucrose animals (squares) compared to controls (circles), unpaired students t-test, ^*P < 0.05, n = 9; control and n = 9; 12 week sucrose. (E) shows a scatter-plot of unchanged mean MSN dendritic tree length (mean ± SEM) from the NAc shell in long-term sucrose animals (squares) compared to controls (circles), unpaired students t-test, P > 0.05, n = 9; control and n = 9; 12 week sucrose. Branch order analysis (mean ± SEM) of dendritic segment number per branch order (F), mean dendritic length per branch order (G) and dendritic spine density per branch order (H). Long-term sucrose consumption decreased dendritic length at distal branch orders (5+) and increased dendritic spine density at distal branch orders (4+) compared to controls (G,H), two-way ANOVAs with Bonferroni post-tests, ^*P < 0.05, ^**P < 0.01, n = 9; control and n = 9; long-term sucrose. Scale Bars: (A, B) = 20 μm; inset of (A, B) = 10 μm; (C) = 1 mm.