The potential effects of gender, season and age on blood parameters were characterized for the first time in mouse lemurs through a cross-sectional study.
A comparison of mouse lemur biochemical values to “normal” biochemical blood parameters recorded in other mammals and primate species revealed several similarities and discrepancies depending on the parameter tested. Compared to ranges described for mice and rats (VetScan references for small animals), mouse lemurs had similar levels of albumin, alkaline phosphatase activity, total bilirubin and calcium levels, but mouse lemurs exhibited higher levels of alanine aminotransferase activity, blood urea nitrogen, creatinine and total protein. Compared to other non-human primate species, mouse lemurs had lower albumin and total protein levels than squirrel monkeys (Saimiri sciureus), macaque rhesus (Macaca mulatta) and cynomolgus monkeys (Macaca fascicularis)), while mouse lemurs exhibited higher blood urea nitrogen values relative to these primates (Fiocruz Primate Center
). We also compared the mouse lemur parameters with values observed in chimpanzees
. Creatinine, calcium and total bilirubin did not differ between chimpanzees and mouse lemurs. However, levels of glucose, blood urea nitrogen, phosphorus, potassium, total protein, albumin and globulin were higher in mouse lemurs than in chimpanzees. The most important difference in these species was the alanine aminotransferase activity; this activity was approximately five times higher in mouse lemurs compared to other primate species. The liver is the site of many biochemical and enzymatic activities, and it represents 2% of the total body weight in humans and approximately 8% of the total body weight of the mouse lemur (unpublished data). This discrepancy in the liver weight/body weight ratio may explain the high levels of alanine aminotransferase in the mouse lemur. In addition, stress is a key factor causing variations in blood parameter measurements; thus, anesthesia is often used prior to sample collection. In this study, however, anesthesia was not used. Breeding animals are accustomed to repeated handling, and not using anesthesia prevented disruptions in blood metabolite concentrations due to active anesthetics.
In mouse lemurs, no sex-specific differences were observed in blood biochemical values except for creatinine levels, which were higher in females. In many species, serum creatinine levels have been shown to be generally higher in males (non-human primates
[21, 22]; apes
; and humans
). This gender difference is due to higher muscle mass and increased turnover in males compared to females
. It is noteworthy that female M. murinus are heavier than males, both in the wild
 and in captivity, regardless of the season. However, despite a significant 20% higher body mass in females, no relationship between body mass and creatinine levels was found. This result suggests that either female body mass is not related to increased free fat mass or that other parameters are involved.
Almost half of the 14 parameters studied were impacted by seasonality and could be related to life history traits of mouse lemurs, especially seasonal variations in energy balance and fat storage during the resting season
In mouse lemurs, glucose and phosphorus levels were higher in the long-day photoperiod. These two parameters are closely related to nutrition or malnutrition in mammals. Despite the fact that blood samples were collected when animals were fasting, high glucose values observed in the summer reflect the increase in food intake during the breeding season. This elevated glucose level during the summer has been previously observed in the black bear, which presented with higher glucose levels during the pre-denning season (July-December)
. In the brown hare (Lepus europaeus), the highest glucose and phosphorus concentrations were observed in summer and the lowest values were obtained in the fall
. As for glucose, higher levels of phosphorus in the summer are related to changes in food intake and to modifications in the regulation of energetic metabolism. Moreover, the relationship between blood glucose and body mass in mouse lemurs in the winter season is consistent with the known relationships between body fat (white adipose tissue) and glucose and food intake, which has been previously shown in mouse lemurs
Additionally, albumin, globulin and total protein levels were significantly higher during the winter season. The significant increase in albumin, globulin and key proteins regulating the colloidal osmotic pressure of blood may be due to the reduction of water consumption and food intake during the winter. Both of these factors have an effect on blood composition and osmolarity by increasing the concentration of certain blood components. Seasonal effects modifying albumin levels have been reported in birds (Columba livia), with low values reported in the winter
. In mouse lemurs, the marked seasonal rhythm is related to physiological outputs, particularly plasma hormone concentrations of IGF-1 and sexual hormones
. Changes in hormone concentrations may lead to significant alterations in protein turnover due to high metabolism in response to differences in photoperiod. However, albumin may consistently vary according to environmental factors such as housing conditions (non-human primates
). Moreover, total protein levels may reflect nutritional status as well as kidney and liver functions; low levels of total protein may indicate liver, kidney or absorption disorders. In mouse lemurs, high protein content values during the winter may also be linked to changes in renal function or decreases in muscle mass from less motor activity. High protein content in the winter could also be related to the fact that endogenous lipids are the main source of energy utilized, and proteins are spared during this period
All of the observed seasonal differences in blood biochemistry in mouse lemurs reflect adaptive seasonal changes in energy balance, and these differences do not appear to be clinically significant.
Total blood urea nitrogen, globulin and creatinine levels were increased in old animals, independently of gender. These parameters are relevant markers of renal function and are known to decline with age. In mammals, decreased renal function is associated with a drop in glomeruli numbers and decreased renal blood flow and pressure; these changes occur as a result of modified cardiac function or persistent vasoconstriction. In the literature, age-related increases in these markers have been previously observed (BUN, human
; GLOB, black bear
, and humans
; CRE, non-human primates
 and humans
Age-related alterations in renal function have been observed in mouse lemurs, and most deaths in captivity are due to renal insufficiency
. Chronic kidney disease in older animals may explain the age-related increase in creatinine levels.