ABSTRACT
To observe the effect of Shudihuang on behaviors and expression of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of attention deficit hyperactivity disorder (ADHD) model rats. Thirty 4-week-old spontaneous hypertension rats (SHR) were randomly divided into model group, methylphenidate hydrochloride (MPH, 2 mg·kg⁻¹·d⁻¹) and Shudihuang group (2.4 g·kg⁻¹·d⁻¹). Another 10 Wistar-Kyoto (WKY) rats were selected as normal control group. The 0.5% CMC-Na solution was administered to model group and WKY rats (2 mL·kg⁻¹·d⁻¹). All of the rats were treated for 4 weeks. The open field test was performed at the 14th and 28th days after gavage, in order to evaluate the spontaneous and impulsive behaviors. Subsequently, gene and protein expressions of BDNF/TrkB and NRG-3 were tested by RT-qPCR and Western blot. Compared with model group, MPH and Shudihuang groups showed significant reduction in total distance, mean velocity and central distance in the open field test (<0.05), and Shudihuang group displayed a shorter central distance than MPH group (<0.05). RT-qPCR and Western blot analysis indicated that expressions of BDNF/TrkB and NRG-3 were lower in prefrontal cortex and striatum of SHR compared with WKY rats. Four weeks later after administration, both Shudihuang and MPH significantly elevated mRNA and protein expressions of BDNF/TrkB and NRG-3 (<0.05).In conclusion, neurodevelopmental disorder mediated by BDNF/TrkB and NRG-3 was closely related with SHR rats' behaviors. Shudihuang may ameliorate the spontaneous and impulsive behaviors by up-regulating the expressions of BDNF/TrkB and NRG-3 and improving growth and maturation of neurons in SHR.
ABSTRACT
Objective To evaluate the method of controlled cortical impact(CCI) on long term cognitive disorder after traumatic brain injury(TBI) and to investigate the possible pathological mechanism.Methods Sixty male SD rats were randomly assigned into 3 groups:sham surgery group(n =10),control group (n =10) and CCI group(n =40).CCI application was used to make the bilateral frontal lobe controlled cortical impact model (depth:1.5 mm,velocity =3.5 m/s,dwell time =400 ms).Morris water maze test and Nissl's staining was used to assess the cognitive function and pathological changes after 8 weeks of CCI.The expressions of brain derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) mRNA in frontal lobe and hippocampus tissue was detected by reverse transcription polymerase chain reaction(RT-PCR).Results The mortality in CCI group was only 12.5％.Morris water maze test results showed the escape latency in CCI group was longer than that in sham surgery and control groups(F =51.784,P ＜ 0.05).Percent of time spend in goal quarter during probe trial in CCI group was significantly less than that in sham surgery and control groups(F =13.468,P ＜ 0.05).Nissl's staining showed frontal lobe had obviously defects; Nissl's bodies of frontal cortex and CA1 region in hippocampus reduced.The expressions of BDNF and TrkB mRNA in frontal lobe and hippocampus were significantly less than those in sham surgery and control groups(P ＜ 0.05).Conclusions The CCI model can be applied for study on long term cognitive disorder after TBI with good stability and repeatability.Using the experimental parameters of CCI can damage the long term cognitive function after TBI in rats,and lead the pathology changes of brain tissue clearly.This may have some relationship with the expressions of BDNF and TrkB mRNA.
ABSTRACT
Objective To investigate the effect of chronic and unpredictable pre-gestational stress on the serum cortisol level of the offspring,as well as the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) in hippocampus when they were 2 month old.Methods Adult female SD rats were divided randomly into 2 groups:the control group and the chronic unpredictable stress (CUS) model group.All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All offspring rats were sacrificed when 2-month old.Serum cortisol (COR) levels were determined by using a standard radioimmunoassay kit.The expressions of BDNF and TrkB in hippocampus were studied by immunoreactivity quantitative analysis.Results 1.After CUS procedure,CUS group showed decreasing activities in the open field test and decreasing sucrose consumption in sucrose intake test compared to the control group and before CUS procedure.2.The serum COR levels in the female offspring rats of CUS group (128.9 ± 7.3) μg/L were higher than those of the control group (119.9 ± 9.0) μg/L,as well as the male offspring of CUS group(116.5 ± 10.9) μg/L compared with the control group(105.4 ± 10.4) μg/L,but the body weight and brain weight between the offspring of 2 groups were not statistic significance.3.Immunoreactivity quantitative analysis showed that the gray values of BDNF in the female offspring of CUS group (36.1 ± 8.5) decreased compared with the control group(42.4 ± 6.9),as well as the male offspring of CUS(39.6 ± 8.4)compared with the control group (43.7 ± 6.4).4.The gray values of TrkB in the female offspring of CUS group (47.1 ± 2.9) decreased than the control group(50.2 ± 3.9),as well as the male offspring of CUS (46.5 ± 6.7)compared with control group(50.5 ± 5.4).Conclusion Pre-gestational stress reduced the expressions of BDNF and TrkB in hippocampus of the offspring which may relate to hypothalamic pituitary adrenal.