Prenatal Exposure to Fenugreek Impairs Sensorimotor Development and the Operation of Spinal Cord Networks in Mice

Loubna Khalki,Jean-Charles Viemari,Zahra Sokar,Laurent Vinay,Mohamed Bennis,Hélène Bras,Saadia Ba M’Hamed,Thomas H Gillingwater

doi:10.1371/journal.pone.0080013

Abstract

Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE) or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments.

Highlights

Fenugreek (Trigonella foenum graecum) is one of the oldest traditional medicinal plants, cultivated in India, the Mediterranean region, North Africa and Yemen (Kassem et al, 2006)
We tested the influence of fenugreek seeds aqueous extract (FSAE) exposure on sensorimotor tests performed during the postnatal period to evaluate the proper development of the sensorimotor capacities
The time required for the surface righting response significantly decreased with age in controls (Spearman Test, P = 0.0049) whereas it did not significantly change in FSAE treated mice (Spearman Test, P = 0.15)

Summary

Introduction

Fenugreek (Trigonella foenum graecum) is one of the oldest traditional medicinal plants, cultivated in India, the Mediterranean region, North Africa and Yemen (Kassem et al, 2006). We previously demonstrated that prenatal exposure to fenugreek seeds produced neurobehavioral alteration at P21 including decreased locomotor activity, impaired motor coordination and spatial short term memory [10]. Because of the widespread use of fenugreek seeds for its therapeutic actions during pregnancy, it is important to study the effects of FSAE on the development of neuronal networks such as the spinal locomotor network. During the first postnatal week, spontaneous locomotor activity consists of crawling movements [11]. During this period, the hindlimbs remain passive. At early postnatal days (P0-P3), we investigated whether spontaneous and locomotor-like activities were altered after prenatal exposure to FSAE. We assessed static and dynamic changes in juvenile (P21) and young adults (P41) using the CatWalk analysis

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