Effects of Topiramate on Mouse Eccrine Sweat Gland Responsiveness to Heat Exposure

Abstract

Young mice (2 weeks old) were given topiramate daily for 1 month, and sudomotor function was evaluated utilizing impression mould techniques to determine the number of sweat glands reactive to heat exposure and sweat output per gland on the plantar surface of mice hind-paws. Immunohistochemical quantitation of protein gene product 9.5, choline acetyltransferase and tyrosine hydroxylase in footpads was determined after topiramate treatment. While a 25% decrease in the number of secreting sweat glands and a 42% decline in sweat output per gland were observed following topiramate treatment, no significant differences were noted in sudomotor innervation, expressed as length of choline acetyltransferase, tyrosine hydroxylase and protein gene product 9.5 immunoreactive nerve profiles in single secretory coils or in sweat gland sizes within the secretory coil area. Long-term topiramate stimulation resulted in a reduction in the number of reactive sweat glands, without changes in sweat gland innervation, suggesting that the diminished responsiveness of the glands to heat exposure induced by topiramate might have resulted from a decrease in the intrinsic regulatory activity of sweat glands, as opposed to the loss of periglandular neurotransmitters or the impairment of the structure of the glands. [12][13][14][15][16][17]. While the effect was reversible, and disappeared with the cessation of the treatment, the mechanism underlying this effect on sweating has not been fully elucidated. The ability of human beings to dissipate heat during exercise and in hot environments depends mainly on the evaporation of sweat secreted by eccrine sweat glands. Consequently, sweat production is essential for heat tolerance, preventing hyperthermia, and influences performance during physical activity [18]. Sweat glands are innervated by sympathetic postganglionic axons, which, in contrast to the ordinary sympathetic innervation, use acetylcholine as the principal neurotransmitter [19][20][21].In the current study, we investigated the effects of topiramate on the responsiveness of mouse eccrine sweat glands to heat exposure and evaluated sudomotor function utilizing silicone imprints, a method that allows accurate quantitation of sweat gland secretion repeatedly over time, and following different types of nerve lesions or treatments [22][23][24][25][26][27]. Additionally, immunolabelling was used to examine the effects of topiramate on choline acetyltransferase (ChAT) in cholinergic sudomotor nerves, tyrosine hydroxylase (TH) in noradrenalinergic nerves, as well as total innervation of sweat glands (protein gene product 9.5, PGP9.5) and sweat gland acinar size. The aim of this study was to investigate whether topiramate reduced the responsiveness of the glands to heat exposure in mice, and whether the effects on the eccrine sweat glands were related to changes in periglandular neurotransmitters and/or sweat gland structure. Materials and MethodsExperimental design. Animals were housed under standard conditions with water and foo...

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