(-)-Deprenyl Alters the Time Course of Death of Axotomized Facial Motoneurons and the Hypertrophy of Neighboring Astrocytes in Immature Rats

Abstract

(-)-Deprenyl previously was shown to increase the survival of rat facial motoneurons (FMns) after a loss of muscle-derived trophic support caused by axotomy at Postnatal Day 14 (P14) and to increase reactive astrogliosis after traumatic damage to the adult rat striatum. We estimated reactive astrogliosis in facial nuclei at 1, 3, 7, 14, and 21 days after transection of the facial nerve at P14 by two methods: first, by measuring the relative optical density (OD) of GFAP immunoreaction (GFAP-OD) in the facial nuclei and second by determining the relative area of GFAP immunoreactivity (GFAP-AREA) in the same nuclei. Both measures were taken for multiple immunoreacted sections through the length of each facial nuclei by using a control half section at the same brain stem level taken from an unlesioned, age-matched animal. The experimental and control facial nuclear half sections were coimmunoreacted using the "glued" half brain stem method. The facial nerve transections served to axotomize all of the FMns in the ipsilateral facial nuclei. The numbers of surviving FMns were examined at the same time points as above using counts of Nissl-stained somata from serial sections taken through each facial nucleus. We found that FMn loss occurred rapidly after axotomy in saline-treated animals and could be best fitted with a decaying exponential relationship (time constant 2.7 days). In the saline-treated animals, the FMn loss plateaued between 7 and 14 days at 74.8%, and 47% of the FMns were found to be lost within 3 days. Increases in the facial nuclear GFAP-OD values and GFAP-AREA values were evident as early as 1 day following axotomy (2.5 and 3.3 times normal, respectively) and reached maximal levels by 7 days (5.7 and 37.6 times normal, respectively). The administration of (-)-deprenyl slowed the loss of the FMns by 24-48 h (time constant 3.9 days) and increased the number of surviving FMns at 21 days by 2.1 times. Treatment with (-)-deprenyl was found to significantly increase GFAP-OD and GFAP-AREA at Day 1 by 71 and 32%, respectively, and at Day 3 by 22 and 27%, respectively. In contrast, it decreased GFAP-OD and GFAP-AREA by 42 and 19%, respectively, at Day 7, and by 20 and 12%, respectively at Day 21. Accordingly, as estimated by both measures, the drug increases reactive astrogliosis in the facial nucleus during the first 3 days after facial nerve transection and decreases the gliosis thereafter. The increased astrogliosis at Days 1 and 3 may contribute to the increased survival of the axotomized, immature FMns caused by (-)-deprenyl over the same time period.