Translating the impact of exercise on cognition: methodological issues in animal research.

Physical exercise and fitness have been proposed as potential factors that promote healthy cognitive aging. Some of the support for this hypothesis has come from animal research. Animal studies are also used to propose the physiological mechanisms underlying the cognitive performance improvement associated with exercise. In the present review and meta-analysis, we discuss several methodological problems that limit the contribution of animal studies to the understanding of the putative effects of exercise on cognitive aging. We suggest that the most likely measure to equate exercise intensity in rodent and humans may be oxygen consumption (VO2) because observed values are surprisingly similar in young and older rodents and humans. For practical reasons, several animal studies use young rodents kept in social isolation. We show that social isolation is associated with an enhanced impact of exercise on cognitive performance but not on some physiological measures thought to mediate the effect of exercise. Surprisingly, two months or more of exercise intervention appeared to be ineffective to promote cognitive performance compared to shorter durations. We argue that impact of exercise in socially isolated animals is explained by an alleviation of environmental impoverishment as much as an effect of physical exercise. It is possible that the introduction of exercise in rodents is partly mediated by environmental changes. It may explain why larger effects are observed for the shorter durations of exercise while much smaller effects are found after longer periods of exercise.

Effects of hypoxia-induced gill remodelling on the innervation and distribution of ionocytes in the gill of goldfish, Carassius auratus.

The presence of an interlamellar cell mass (ILCM) on the gills of goldfish acclimated to 7°C leads to preferential distribution of branchial ionocytes to the distal edges of the ILCM, where they are likely to remain in contact with the water and hence remain functional. Upon exposure to hypoxia, the ILCM retracts, and the ionocytes become localized to the lamellar surfaces and on the filament epithelium, owing to their migration and the differentiation of new ionocytes from progenitor cells. Here we demonstrate that the majority of the ionocytes receive neuronal innervation, which led us to assess the consequences of ionocyte migration and differentiation during hypoxic gill remodelling on the pattern and extent of ionocyte neuronal innervation. Normoxic 7°C goldfish (ILCM present) possessed significantly greater numbers of ionocytes/mm(2) (951.2 ± 94.3) than their 25°C conspecifics (ILCM absent; 363.1 ± 49.6) but a statistically lower percentage of innervated ionocytes (83.1% ± 1.0% compared with 87.8% ± 1.3%). After 1 week of exposure of goldfish to hypoxia, the pool of branchial ionocytes was composed largely of pre-existing migrating cells (555.6 ± 38.1/mm(2)) and to a lesser extent newly formed ionocytes (226.7 ± 15.1/mm(2)). The percentage of new (relative to pre-existing) ionocytes remained relatively constant (at ∼30%) after 1 or 2 weeks of normoxic recovery. After hypoxia, pre-existing ionocytes expressed a greater percentage of innervation than newly formed ionocytes in all treatment groups; however, their percentage innervation steadily decreased over 2 weeks of normoxic recovery.

The interactive effects of exercise and gill remodeling in goldfish (Carassius auratus).

Gill remodeling in goldfish (Carassius auratus) is accomplished by the appearance or retraction of a mass of cells (termed the interlamellar cell mass or ILCM) between adjacent lamellae. Given the presumed effects of gill remodeling on diffusing capacity, the goals of the current study were (1) to determine the consequences of increased aerobic O(2) demand (swimming) on gill remodelling and (2) to assess the consequences of the presence or absence of the ILCM on aerobic swimming capacity. Fish acclimated to 7 °C exhibited a marked increase in the ILCM which occupied, on average, 70.0 ± 4.1% of the total interlamellar channel area in comparison to an average ILCM area of only 28.3 ± 0.9% in fish acclimated to 25 °C. Incrementally increasing swimming velocity in fish at 7 °C to achieve a maximum aerobic swimming speed (U (CRIT)) within approximately 3 h resulted in a marked loss of the ILCM area to 44.8 ± 3.5%. Fish acclimated to 7 °C were subjected to 35 min swimming trials at 30, 60 or 80% U (CRIT) revealing that significant loss of the ILCM occurred at swimming speeds exceeding 60% U (CRIT). Prior exposure of cold water-acclimated fish to hypoxia to induce shedding of the ILCM did not affect swimming performance when assessed under normoxic conditions (control fish U (CRIT) = 2.34 ± 0.30 body lengths s(-1); previously hypoxic fish U (CRIT) = 2.99 ± 0.14 body lengths s(-1)) or the capacity to raise rates of O(2) consumption with increasing swimming speeds. Because shedding of ILCM during U (CRIT) trials complicated the interpretation of experiments designed to evaluate the impact of the ILCM on swimming performance, additional experiments using a more rapid 'ramp' protocol were performed to generate swimming scores. Neither prior hypoxia exposure nor a previous swim to U (CRIT) (both protocols are known to cause loss of the ILCM) affected swimming scores (the total distance swum during ramp U (CRIT) trials). However, partitioning all data based on the extent of ILCM coverage upon cessation of the swimming trial revealed that fish with less than 40% ILCM coverage exhibited a significantly greater swimming score (539 ± 86 m) than fish with greater than 50% ILCM coverage (285 ± 70 m). Thus, while loss of the ILCM at swimming speeds exceeding 60% U (CRIT) confounds the interpretation of experiments designed to assess the impact of the ILCM on swimming performance, we suggest that the shedding of the ILCM, in itself, coupled with improved swimming scores in fish exhibiting low ILCM coverage (<40%), provide evidence that the ILCM in goldfish acclimated to cold water (7 °C) is indeed an impediment to aerobic swimming capacity.