Protein-Energy Malnutrition Causes Deficits in Motor Function in Adult Male Rats

Abstract

Background: Adult protein-energy malnutrition (PEM) often occurs in combination with neurological disorders affecting hand use and walking ability. The independent effects of PEM on motor function are not well characterized and may be obscured by these comorbidities.

Objective: Our goal was to undertake a comprehensive evaluation of sensorimotor function with the onset and progression of PEM in an adult male rat model.

Methods: In Expt. 1 and Expt. 2, male Sprague-Dawley rats (14-15 wk old) were assigned ad libitum access for 4 wk to normal-protein (NP) or low-protein (LP) diets containing 12.5% and 0.5% protein, respectively. Expt. 1 assessed muscle strength, balance, and skilled walking ability on days 2, 8, and 27 by bar-holding, cylinder, and horizontal ladder walking tasks, respectively. In addition to food intake and body weight, nutritional status was determined on days 3, 9, and 28 by serum acute-phase reactant and corticosterone concentrations and liver lipids. Expt. 2 addressed the effect of an LP diet on hindlimb muscle size.

Results: PEM evolved over time in rats consuming the LP diet. Total food intake decreased by 24% compared with the NP group. On day 28, body weight and serum albumin decreased by 31% and 26%, respectively, and serum α2-macroglobulin increased by 445% (P < 0.05) in the LP group compared with the NP group. Forelimb dysfunction (173% increase in adaptive flexed-arm-hang score) developed on day 2 in rats fed the LP diet (P < 0.001), whereas abnormal walking (34% decreased incidence of correct hindlimb placement) developed by day 27 (P < 0.05). Relative to the NP diet, the LP diet reduced the cross-sectional area of gastrocnemius medialis (P < 0.05).

Conclusions: PEM in adult male rats causes a variety of sensorimotor abnormalities that develop at different stages of malnutrition. This model can be used in combination with disease models of sensorimotor deficits to examine the interactions between nutritional status, other treatments, and disease progression.

Keywords: acute-phase reactants; motor function; performance-based measures; protein-energy malnutrition; rat model.

FIGURE 1

Temporal profile of body weight (A) and food intake (B) in adult male rats fed an LP or an NP diet for 28 d. The solid lines in panel B correspond to the second-order polynomial curve for NP and LP groups. Values are means ± SEMs, n = 8 rats (A) or n = 4 cages (2 rats/cage) (B) for both groups. The line with an asterisk above corresponds to the period in which the LP and NP groups were significantly different. *P < 0.05. B, baseline (day 0); LP, low-protein; NP, normal-protein.

FIGURE 2

Progression of serum concentrations of albumin (A), A2M (B), and CORT (C) in adult male rats fed an LP or an NP diet for 28 d. Serum CORT is expressed as a percentage of day 3 concentrations. Values are means ± SEMs, n = 8 for each group. *^,**^,***Difference between NP and LP groups: *P < 0.05, **P < 0.01, ***P < 0.001. A2M, α2-macroglobulin; CORT, corticosterone; LP, low-protein; NP, normal-protein.

FIGURE 3

Evolution of pull-up scores in a bar-holding task in adult male rats fed an LP or an NP diet for 28 d. Values are means ± SEMs, n = 8 for each group. *^,**^,***Difference between NP and LP groups: *P < 0.05, **P < 0.01, ***P < 0.001. B, baseline; LP, low-protein; NP, normal-protein.

FIGURE 4

A temporal characterization of skilled forelimb (A) and hindlimb (B) use and body posture (C) in the horizontal ladder walking task in adult male rats fed an LP or an NP diet for 28 d. Values are means ± SEMs, n = 8 for each group. *^,***Difference between NP and LP groups: *P < 0.05, ***P < 0.001. B, baseline; LP, low-protein; NP, normal-protein.

FIGURE 5

Cross-sectional area of hindlimb muscles in adult male rats fed an LP or an NP diet for 26 d. Values are means ± SEMs, n = 4 (NP) and n = 7 (LP). *^,**Difference between NP and LP groups: *P < 0.05, **P < 0.01. GC, gastrocnemius; GCl, gastrocnemius lateralis; GCm, gastrocnemius medialis; LP, low-protein; NP, normal-protein; Pl, plantaris; Sol, soleus.