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.