(-)-DEPRENYL ALTERS THE TIME-COURSE OF DEATH OF AXOTOMIZED FACIAL MOTONEURONS AND THE HYPERTROPHY OF NEIGHBORING ASTROCYTES IN IMMATURE RATS

(-)-Deprenyl previously was shown to increase the survival of rat faci al motoneurons (FMns) after a loss of muscle-derived trophic support c aused by axotomy at Postnatal Day 14 (P14) and to increase reactive as trogliosis after traumatic damage to the adult rat striatum. We estima ted 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, b y measuring the relative optical density (OD) of GFAP immunoreaction ( GFAP-OD) in the facial nuclei and second by determining the relative a rea of GFAP immunoreactivity (GFAP-AREA) in the same nuclei. Both meas ures were taken for multiple immunoreacted sections through the length of each facial nuclei by using a control half section at the same bra in stem level taken from an unlesioned, age-matched animal. The experi mental and control facial nuclear half sections were coimmunoreacted u sing the ''glued'' half brain stem method. The facial nerve transectio ns served to axotomize all of the FMns in the ipsilateral facial nucle i. The numbers of surviving FMns were examined at the same time points as above using counts of Nissl-stained somata from serial sections ta ken through each facial nucleus. We found that FMn loss occurred rapid ly after axotomy in saline-treated animals and could be best fitted wi th a decaying exponential relationship (time constant 2.7 days). In th e 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. In creases 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 tim es normal, respectively). The administration of (-)-deprenyl slowed th e loss of the FMns by 24-48 h (time constant 3.9 days) and increased t he number of surviving FMns at 21 days by 2.1 times. Treatment with (- )-deprenyl was found to significantly increase GFAP OD and GFAP-AREA a t Day 1 by 71 and 32%, respectively, and at Day 3 by 22 and 27%, respe ctively. 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. A ccordingly, as estimated by both measures, the drug increases reactive astrogliosis in the facial nucleus during the first 3 days after faci al nerve transection and decreases the gliosis thereafter. The increas ed astrogliosis at Days 1 and 3 may contribute to the increased surviv al of the axotomized, immature FMns caused by (-)-deprenyl over the sa me time period. (C) 1994 Academic Press, Inc.