Changes of neuronal nitric oxide synthase in relevant cerebral regions in spontaneous senile dementia model and regulation of Tiantai Ⅰ

Zhengzhi WU; Ming LI; Xiuqin JIA; Yongfeng ZHANG

ABSTRACT

BACKGROUND:

Neuron nitrogen monoxide(NO) is related to synaptic plasticity and is the key transmitter of normal learning and memory.Neuronal nitric oxide synthase(nNOS) is the biological synthetic enzyme of NO in neurons.The reports have been fewer yet on cerebral nNOS activity in Alzheimer disease(AD) patients,especially on changes in positive neural fibers of nNOS in temporal lobe cortex and hippocapmus CA1 region.

OBJECTIVE:

To observe cerebral nNOS activity in AD patients, especially on changes in positive neural fibers of nNOS in temporal lobe cortex and hippocapmus CA1 region and effects of Tiantai Ⅰ on nNOS activity.

DESIGN:

A randomized and controlled trial.

SETTING:

Institute of Collaboration of Chinese and Western Medicine, Shenzhen City. MATERIALSThe experiment was performed in No.2 Grade Animal Experimental Room of Institute of Collaboration of Chinese and Western Medicine,Shenzhen City.A total of 65 Kunming mice were employed in the experiment.

METHODS:

The experimental animals were bred till 21 months old and the mice with senile dementia were screened from the aged ones according to the international general standards and methods.The experimental animals were randomized into 4 groups,named as senile dementia group,western drug control,group with small dosage of Tiantai Ⅰ and group with large dosage of Tiantai Ⅰ .In addition,a group with normal learning and memory of the senile mice(simply called senile normal group) was designed.There were 13 mice in each group.In western drug control,hydergine 0.6 mg/kg was prescribed; in the groups of small and large dosage of Tiantai Ⅰ ,the dosages were 6.80 g/kg and 20.41 g/kg respectively,continuously for 60 days.In senile normal group and senile dementia group,the bi distilled water of equal dosage was applied for perfusion.The scores of learning and memory were determined by step down test. Slices of brain tissues were prepared with frozen,nNOS activity was displayed by NBT histochemistry method and the analysis was done systematically with auto micrography in quantity.

RESULTS:

Learning and memory were significantly decreased in mice with senile dementia(P< 0.01),the positive reaction of nNOS was remarkably weaker compared with normal aged mice.It was the first time to discover that the surface densities of nNOS positive neural fibers in temporal lobe cortex and hippocampus CA1 region [(9.48± 2.09),(5.11± 2.74) respectively]were remarkably lower than those of the normal aged mice [(17.75± 3.47),(11.95± 2.00) respectively](P< 0.01). Simultaneously, it was also the first time to discover that normal correlation was apparent between nNOS activity of cortex and hippocampus and the scores of learning and memory.Tiantai Ⅰ could significantly increase the surface densities of nNOS positive neural fibers in cortex and hippocampus in senile dementia mice, of which, the values of the small dosage were (11.57± 2.44) and (8.18± 2.92) respectively and of the large dosage were (12.59± 2.88) and (9.33± 2.18) respectively,(P< 0.01- 0.05).

CONCLUSION:

The hypo activity of central nNOS in senile dementia mice resulted in significantly decreased positive neural fibers of nNOS in cerebral cortex and hippocampus.The surface densities of nNOS positive neural fibers in temporal lobe cortex and hippocampus CA1 region were significantly related to the scores of learning and memory.Tiantai Ⅰ could remarkably improve the disturbance of learning and memory in spontaneous senile dementia model and enhance its nNOS activity in cerebral cortex and hippocampus.