[The postnatal development of perineuronal net, Nogo receptor and the effect of fluoxetine on remodeling it in the visual cortex of rats].

Objective To investigate the postnatal development of perineuronal net (PNN), Nogo receptor (Nogo R) in visual development and the effect of fluoxetine(Flx) on remodeling it in the visual cortex of adult rats. Methods Experimental study. (1) Wistar rats were divided into postnatal weeks (PW)1,PW3,PW5,PW7,PW9 group (8 rats in each group) according to the age of PW. The changes of PNN and Nogo R were observed in the visual cortex of each group. (2) The adult rats (10 weeks after birth) were randomized into Flx 0W, Flx 2W, Flx 4W, Flx 6W and Flx 8W group (8 rats in each group) according to Flx administrational weeks. The influence of Flx on the expression of PNN and Nogo receptor in the visual cortex was detected by immunofluorescence and western blots. (3) The adult rats were randomized into Cont (negative control), Flx, binocular form deprivation(BFD,positive control) and BFD+Flx group (8 rats in each group). Flx group accepted oral administration at the dosage of 0.2 mg/ml once per day for 4 weeks. The eyelids were binocularly sutured for 2 weeks to form the BFD group, and the combination of Flx administration and BFD was performed in the BFD+Flx group.No intervention was conducted in the control group (Cont group). Immunofluorescence was used to observe the expression pattern of PNN staining by biotinylated wisteria floribunda lectin (WFA). The expression of Nogo R in the visual cortex was detected by immunofluorescence and Western blots. The expression of PNN and Nogo R were examined in each group. And t test, analysis of variance and rank sum test were employed for inter-group comparison based on the homogeneity of variance. Bonferroni method was used for multiple comparison and simple linear regression analysis was used for the trend. Results (1) The expression of PNN (standardized b=0.97, P=0.005) and Nogo R (standardized b=0.96, P=0.010) increased during the postnatal development and the Nogo R reached the matured level at PW7 (PW7 vs. PW9, 131.83±3.78 vs. 135.11±3.92, Z=1.93, P=0.062). (2) Flx significantly decreased PNN in the visual cortex of adult rats. The density of PNN-positive cells in the visual cortex of healthy adult rats fed with Flx for 4 weeks was (86.22±7.68)/mm2, which was similar to that of 3 weeks old rats [(84.21±6.68)/mm2, t=2.08, P=0.073]. The expression of PNN (standardized b=-0.88, P=0.040) and it′s receptor Nogo R (standardized b=-0.90, P=0.007) decreased with prolongation of Flx use. (3) The expression of Nogo R (t=13.42,11.47, 18.13; P=0.012, 0.013, 0.001; Flx, BFD and BFD+Flx group vs. Cont group) and the density of PNN (t=10.09, 7.64, 13.01; P=0.007, 0.011, 0.001; Flx, BFD and BFD+Flx group vs. Cont group) could be modulated by Flx and BFD after the critical period. There are no differences in BFD and Flx group on Nogo R changes (t=2.41, P=0.153). The expression of Nogo R protein was also different among the 4 groups (H=5.69, P=0.041). The effect of Flx combined with BFD was better than the Flx or BFD alone (Flx vs. BFD+Flx, Z=4.22, P=0.005; BFD vs. BFD+Flx, Z=3.09, P=0.010). Conclusions The expression of PNN and Nogo R increase during the postnatal development. Chronic Flx treatment decrease the expression of PNN and Nogo R after the critical period in the visual cortex of adult rats, that is the same as BFD. (Chin J Ophthalmol, 2019, 55:37-45) Key words: Visual cortex; Nogo receptors; Neuronal plasticity; Fluoxetine; Perineuronal net