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Iranian Journal of Pathology (2007)2 (2), 45- 48 Original Article
Deprenyl Can Mediate Neuronal Protection Rather
than Neuronal Rescue
Marjan Heshmati1, Hesam Amini1
1.Dept. of Anatomy, School of Medicine, Shahed University, Tehran, Iran ABSTRACT
Background and Objective: Deprenyl is a drug for the treatment of Parkinson’s disease, where
the dopaminergic neurons are the target of this drug. Several reports also documented that deprenyl has an effect on the sensory and motor neurons. There are some reports about the mode of action of deprenyl on motoneurons as a neuroprotective agent, while others believe that deprenyl acts as a Materials and Methods: In this experimental study, the axotomized spinal motoneurons in rat
neonates were used to investigate the mode of action of deprenyl on motoneurons. Six groups of newborn rats (5 each) were used in this study. The first group was treated with 2.5 mg/kg of drug (for 21 days) one hour before surgical transection of the left sciatic side, the second treated at the time of surgery, and the third one treated one hour after surgery. The fourth, fifth, and sixth groups were given normal saline 1 hour before the surgery, at the time of surgery, and 1 hr after the surgery respectively. The animals were perfused and spinal cords were removed. The tissues were processed in paraffin and then sectioned. Tissues were stained with Cresyl violet. Total motoneuron count was done and the percentage of motoneuron reduction as well as motoneuron survival index was calculated.
Results: The obtained data revealed that deprenyl in pre-treated group was more effective than in
Conclusion: Taken together, deprenyl is more neuroprotective than neurorescuer of spinal
Key words: Deprenyl, Spinal cord, Neuron
Introduction
been proposed for the mode of action of deprenyl on dopaminergic neurons including direct inhibition Deprenyl is a type B monoamine oxidase inhibitor of MAO-B and subsequent increase in the level of which is used to treat Parkinson’s disease (1), dopamine in these neurons (2). The mechanisms of where deprenyl showed a direct effect on dopaminergic anti-oxidant activities were suggested directly by free- neurons (2). The anti-Parkinson’s disease activity of radical scavenging (5, 6), or indirectly by induction of the drug has been demonstrated in animal model (3) free radical scavenging enzymes such as superoxide and in clinical studies (4). Several mechanisms have dismutase (7).
Received: 10 February 2007Accepted: 25 April 2007Address communications to: Dr. Marjan Heshmati, Shahed University, P.O. Box: 18151/159, Tehran, Iran.
Email: [email protected] IRANIAN JOURNAL OF PATHOLOGY
46 Deprenyl Can Mediate Neuronal Protection Rather than Neuronal Rescue
On the other hand, deprenyl-treated axotomized- of motoneuron reduction was also calculated (8). The motoneurons in the spinal cord of newborn rats showed a therapeutic effectiveness was calculated as follows: sustained increase in the number of the cells as compared Motoneuron survival index = PMR in the saline with those untreated newborns (8). In vitro findings treated group/PMR in the deprenyl treated group.
have confirmed these results (7, 9). The axotomized PMR is the percentage of motoneuron reduction.
adult murine facial motoneurons showed a significant The data were tested for normality using S-K test increase in the number of neurons at the axotomized and analyzed using Student’s t-test and analysis of motoneuron treated with deprenyl as compared with variance.
those untreated ones (10). The investigation on the sensory neurons revealed similar findings in dorsal root ganglion where the number of the neurons in the The results showed that the total number of moton- transected animals treated with deprenyl showed higher eurons in deprenyl treated group at the axotomized neuronal number in comparison with untreated ones (11). side was significantly higher than those of untreated Also, Buys et al. (12) reported that deprenyl increases animals. Total number of motoneurons in intact side the survival of rat retinal ganglion cells following optic (control) was higher than axotomized side in all 6 nerve crush. These observations indicated that deprenyl groups. A similar trend was noticed in the percentage can increase the survival of neurons after trauma. While, of motoneuron reduction (Table 1). The percentage of some investigators proposed that deprenyl protects the motoneurons reduction in pre-surgery treatment group axotomized motoneurons (8, 13) and others assumed was significantly lower than the post-surgery treated that deprenyl rescues these neurons (14, 15, 16).
groups, while it was insignificantly lower than those Therefore, the purpose of this study was to elaborate treated at surgery. The motoneuron survival index in the mode of deprenyl action regarding neuroprotection the pre-surgery treatment group (1.7) was higher than versus neurorescue of axotomized motoneurons.
those treated at surgery time and post-surgery treatment group (1.6 and 1.4 respectively).
Materials and Methods
Sprague-Dawley rats were purchased from Razi Table1. The means and standard deviations of
Institute (Karaj, Iran), kept in the Shahed University total motoneurons count (TMC) at the axotomized
animal house, and handled according to the guidelines (ax) and un-axotomized (un) sides in pre-surgery
of the university ethical committee. Six groups (5 treatment (1 h), treated at surgery time, and post-
each) of newborn rats were used in the study, left surgery treated (1 h) were presented as well as the
sciatic nerves were transectioned while the right ones percentage of neuronal reduction (PNR) (means and
kept intact and used as controls. The animals were standard deviations) and motoneuron survival index
anesthetized by hypothermia and the surgery was done (MSI) (ratio) in the same groups.
on day 3 postnatal. The first group was treated daily
Ux and ax denote un-axotomized and axotomized
with deprenyl 2/5 mg/kg one hour before the surgery by group¸ D and S indicate deprenyl and saline normal-
intraperitoneal injection, the second group was treated treated groups respectively.
at the surgery time, and the third group was treated one
hour after the surgery. The treated rats were maintained
Pre-surgery At surgery Post-surgery
Parameters
for 21 days. The animals were sacrificed using general treatment
treatment
treatment
anesthesia. Accordingly, the fourth, fifth, and sixth TMC-ux-D 1577±79*
groups were injected with normal saline similar to the protocols of the treated animals. The L4-L6 spinal TMC-ax-D
segments were removed by laminectomy and perfused TMC-ux-S
with Karnivasky`fixative and then in buffered formalin, processed in paraffin, cut (8 mm), and stained with TMC-ax-S
Motoneurons in axotomixed and intact sides were counted, one from five sections in each slide was counted and then according to Panahi and Al-Tiraihi (8) total motoneurons calculated, and the percentage IRANIAN JOURNAL OF PATHOLOGY
The statistical differences in TMC between the protocol in axotomized spinal motoneurons (8), injured axotomized and un-axotomized sides were significant motoneurons due to spinal cord ischemia (24), and in all groups (Treated group *) (untreated group •).
axotomized facial motoneurons (10). In this study, pre- The statistical differences in TMC between the un- surgery treatment protocol was used to evaluate the axotomized sides in pre-surgery, at-surgery, and post- neuronal loss in the axotomized motoneurons and the surgery in treatment groups and non- treated groups results showed that there is a statistically significant were not significant, while in the axotomized sides, increase in the number of motoneurons in the pre-surgery the statistical differences were significant between pre- treatment group at the axotomized side (Table 1). However, surgery with post and at surgery in treatment groups.
the mechanism of neuroprotection by deprenyl in post- The differences in PNR between pre-surgery and post surgery treatment protocol can not be excluded because and at-surgery in treatment groups were significant. The of the existence of delayed phase of motoneurons death statistical differences in PNR between the pre, post, and in the injured spinal cord (21).
at surgery in saline normal treatment groups were not significant.
Conclusion
The conclusion of this study is that deprenyl is more Discussion
neuroprotective than Neurorescue of spinal moton- The results of this study showed that deprenyl eurons in rat animal model.
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