ABSTRACT
Objective To evaluate the effectiveness of a major depression animal model for old man es?tablished with orchidectomized(ORX) and subsequently olfactory bulbectomized(OBX) rat. Methods Healthy Sprague?Dawley male adult rats were randomly assigned to six groups with ten rats in each group:intact,sham?oper?ated,model,vehicle,fluoxetine plus testosterone propionate(Flu+TP) and amitriptyline plus testosterone propionate (Ami+TP) groups. ORX+OBX rat model was established. Therapy of Flu or Ami (10 mg/kg,i.p.) combined with TP(25 mg/kg,s.c.) was administered. Behavioral changes of rats in each group were detected. Results Open field test: The number of rat crossing lattices in model((124.50±14.25)lattices) or vehicle group( 118.70± 10.27) was significantly larger than those of intact(38.20±6.30),sham?operated(33.70±9.58),Flu+TP (34.00± 9.82) and Ami+TP group (35.20±12.54). The rearing number of model or vehicle group was also significantly larger than those of intact,sham?operated,Flu+TP and Ami+TP group.Statistical differences in the above corre?sponding comparisons of open field test existed (P<0.01). Forced swimming test: The immobility time of model ((131.70±32.44)s) or vehicle group ((135.10±34.01)s) was significantly longer than those of intact((66.60± 12.06)s),sham?operated((62.00±13.38)s),Flu+TP((59.60±8.89)s) and Ami+TP group ((64.80±10.78)s). There were statistical differences in the above corresponding comparisons (P<0.01). Morris water maze test: The escape latency of model((62.00±26.05)s) or vehicle group ((60.52±27.00)s) was significantly longer than those of intact((24.19±9.12)s),sham?operated((21.06±8.13)s),Flu+TP((22.88±8.01)s) and Ami+TP group ((27.04±10.11)s);while the time rat swimming in the quadrant originally put a platform of model or vehicle group was significantly shorter than those of intact,sham?operated,Flu+TP and Ami+TP group. There were statisti?cal differences in the above corresponding comparisons of Morris water maze test (P<0. 01, P<0. 05 ) . Conclusion The above data demonstrates that ORX+OBX rat model is both repeatability and reliability,and can be a major depression animal model of old man for future researches.
ABSTRACT
Objective To investigate the possible abnormal changes of adult neurogenesis in the rostral migratory stream(RMS),in the olfactory bulb and in learning or memory of renovascular hypertensive rat,and to evaluate the possible efficacies produced by intervention of exogenous melatonin.Methods Renovascular hypertensive rat model was established by clamping bilateral renal arteries.Rats were randomly divided into four groups with 10 rats per group:hypertensive,sham-operated,melatonin-treated and normal groups.Morris water maze was used to detect the abilities of learning and memory,and immunohistochemistry for bromodeoxyuridine (BrdU),bromodeoxyuridine plus glial fibrillary acidic protein (BrdU + GFAP) and bromodeoxyuridine plus neurofilament (BrdU + NT) was utilized to examine the changes of the adult neurogenesis in RMS and in the olfactory bulb of each rat.Results The escape latency of hypertensive group ((29.95 ± 20.11) s) recorded in Morris water maze test was the longest in a significant comparison to those of normal group((20.58 ± 19.18)s),sham-operated group ((22.11 ± 20.28) s) and melatonin-treated group ((23.81 ± 22.25) s) (P ＜ 0.05) ; while the time spent by rats during swimming in the quadrant with being originally put platform of hypertensive ((25.51 ± 5.21) s) was the shortest by significant comparison to those of normal((34.67 ± 4.53) s),sham-operated ((33.56 ± 6.12) s) and melatonin-treated group ((36.23 ± 3.86)s) (P ＜ 0.05).Proliferation of neural stem cells (cells/field):the number of BrdU immunoreactive (BrdU-IR) cells of rats in RMS of hypertensive group(34.08 ±6.49) was the smallest,significantly compared with those of normal(43.53 ± 7.56),sham-operated (46.11 ± 4.75) and melatonintreated group (44.30 ± 8.29),(P ＜ 0.05).Differentiation of neural stem cells (cells/slice):the number of BrdU + GFAP-IR cells in olfactory bulb of hypertensive group (2.45 ± 1.32) was largest,significantly compared with those of normal (1.01 ± 0.78),sham-operated (0.68 ± 0.37) and melatonin-treated group (1.35 ± 0.88) (P ＜0.05) ; while the number of BrdU + NF-IR cells in olfactory bulb of hypertensive group (1.15 ± 0.81) was the smallest,significantly compared with those of normal (1.89 ± 0.98),sham-operated(1.63 ± 1.01) and melatonin-treated group (2.30 ± 1.22) (P ＜ 0.05).Conclusion Melatonin can ameliorate the abnormal cognitive behaviors induced by hypertension via a mechanism of reversing the progression of neurogenesis disorders both in RMS and in olfactory bulb,indicating that melatonin may prevent the development of dementia triggered by hypertension.