Sensory Motor Function Disturbances in Mice Prenatally Exposed to Low Dose of Ethanol: A Neurobehavioral Study in Postnatal and Adult Stages

Abstract

Prenatal alcohol exposure (PAE) refers to fetal exposure to alcohol during pregnancy through placental barrier transfer from maternal blood. The postnatal outcomes of PAE differ among exposed individuals and range from overt (serious) alcohol-related behavioral and neurophysiological impairments to covert (silenced) symptoms. The aims of the present investigation were to assess the postnatal neurobehavioral disturbances, particularly, motor coordination and sensory-motor function in mice with PAE. Female mice with positive vaginal plugs were divided into three groups: group 1: Et + Pyr: received two i.p injections of ethanol (1 g/kg) followed by pyrazole (100 mg/kg). Group 2: Pyr: received an i.p injection of pyrazole (100 mg/kg). Group 3: C: of saline controls received, in equal volume, saline solution (NaCl 0.9%). After birth, mice pups were weighed and subjected to behavioral tests for motor function screening using the motor ambulation test, cliff aversion, surface righting, and negative geotaxis, while at the adult stage, mice were subjected to the open field, rotarod, parallel bars, and static rods tests. Our data show an obvious decrement of body weight from the first post-natal day (P1) and continues over the adult stage. This was accompanied by an obvious impaired sensory-motor function which was maintained even at the adult stage with alteration of the locomotor and coordination abilities. The current data demonstrate the powerful neurotoxic effect of prenatal ethanol exposure on the sensory-motor and coordination functions, leading to suppose possible structural and/or functional neuronal disturbances, particularly the locomotor network.

Keywords: behavioral tests; mice; motor activity; motor coordination; prenatal alcohol exposure (PAE); pyrazole.

Figure 1

Experimental design and timeline schedule of the experiments.

Figure 2

Histograms showing the average animal’s body weight. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M. * p < 0.05, *** p < 0.001 vs. C, # p < 0.05, ### p < 0.001 vs. Pyr.

Figure 3

Photography of mice pups at the P15 age from control (A) and ethanol + pyrazole group (B). (C): graphical representation showing the average of animals’ body length. Data are shown as group mean values ± S.E.M. ** p < 0.05 vs. C, *** p < 0.001 vs. C.

Figure 4

Histogram showing the ambulation score in the ethanol + pyrazol (Et + Pyr) (n = 8), the pyrazole (Pyr) (n = 8) and the control (C) groups (n = 8). Data are shown as group mean values ± S.E.M. * p < 0.05 vs. C.

Figure 5

Graphical representation showing the average time spent to turn up in negative geotaxis task. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M. *** p < 0.001 Et + Pyr vs. C. ### p < 0.001 Et + Pyr vs. Pyr.

Figure 6

Graphical representation showing fall avoidance percentage. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M.

Figure 7

Histogram showing the number of rears. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M.

Figure 8

Histograms showing the average time to turn 180° on the static rods. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). (A): Rod (35 mm), (B): Rod (28 mm), (C): Rod (22 mm). Data are shown as group mean values ± S.E.M.** p < 0.01, *** p < 0.001 vs. C, ## p < 0.01 vs. Pyr.

Figure 9

Histograms showing the average time to reach the end of the static rods. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + prazole-treated group (n = 8). (A): Rod (35 mm), (B): Rod (28 mm), (C): Rod (22 mm). Data are shown as group mean values ± S.E.M. *** p < 0.001 vs. C, ### p < 0.001 vs. Pyr.

Figure 10

Histograms showing the average time spent to turn (A) and to reach the end of the parallel bars (B). C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M. ** p < 0.01, *** p < 0.001 vs. C, # p < 0.05, ### p < 0.001, vs. Pyr.

Figure 11

Graphical representation showing the average score in the horizontal bars. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M. * p < 0.05 vs. C. # p < 0.05 vs. Pyr.

Figure 12

Graphical representation showing the latency to fall from the horizontal axe of rotarod. C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M.

Figure 13

Graphical representation showing the number of crossed boxes in the open field (during 5 min observation). C: control (n = 8), Pyr: pyrazole-treated mice (n = 8), Et + Pyr: ethanol + pyrazole-treated group (n = 8). Data are shown as group mean values ± S.E.M. * p < 0.05 vs. C. # p < 0.05 vs. Pyr.