电损毁外侧缰核对帕金森病模型大鼠空间学习记忆功能的影响及其机制

doi:10.13481/j.1671-587X.20210505

Abstract

Abstract: Objective

To observe the effect of electrical lesions of the lateral habenular nucleus （LHb） on the spatial learning and memory functions in the rats with Parkinson’s disease （PD）， and to clarify the role of LHb in the cognitive dysfunction in the PD rats and related mechanism.

Methods

Thirty adult male SD rats were randomly divided into control group， PD group and PD+LHb lesion group，and there were 10 rats in each group. Except control group， the rats in other two groups were used to establish the PD models. The PD rats in PD+LHb lesion group were lesioned using direct current stimulation two weeks after modeling，and the related tests were performed at the 4th week after modeling. The numbers of crossed squares and rearings of the rats in three groups were observed by open field test. The distances to find the hidden platform and the percentages of swimming distance in target quadrant of the rats in three groups were observed by Morris water maze test. The levels of serotonin （5-HT） in the medial prefrontal cortex （mPFC） and hippocampus tissue of the rats in three groups were assessed by neurochemical method. The degeneration of dopamine （DA） neurons in the brain tissue and LHb electrical lesioning were confirmed by the immunohistochemical and histological staining methods.

Results

The results of open field test showed that compared with control group， the numbers of crossed squares and rearings of the rats in PD group were significantly decreased （P<0.01），and the number of crossed squares and rearings of the rts in PD+LHb lesion group had no significantly differences（P>0.05）.The results of Morris water maze test showed that compared with control group， the distances to find the hidden platform in navigation trial of the rats in PD group on the 2nd， 3rd，4th and 5th days were significantly increased （P<0.01）， and the percentages of swimming distance in target quadrant after withdrawal of platform in space exploration experiment were significantly decreased （P<0.05）； but there were no significant differences in the 5-HT levels in the mPFC and hippocampus tissues of the rats between two groups（P>0.05）. There were no significant differences in the numbers of crossed squares and rearings of the rats between PD and PD+LHb lesion groups； compared with PD group， the distances to find the hidden platform of the rats in PD+LHb group on the 2nd， 3rd，4th and 5th days were significantly increased （P<0.01），the percentages of swimming distance in target quadrant after withdrawal of platform were significantly decreased （P<0.05）， and the 5-HT levels in mPFC and hippocampus tissues were significantly decreased （P<0.01）. The immunohistochemical staining results showed the DA neurons of the lesioned side of the PD model rats in the substantia nigra pars compacta were missing， and the number of DA neurons in ventral tegmental area was lower than that in unlesioned side （P<0.01）.The histological staining results showed the LHb was partially lesioned.

Conclusion

LHb lesions can aggravate the impairment of spatial learning and memory functions of the rats with PD， and its mechanism may be related to the changes of levels of 5-HT transmitter in the related brain regions.

Key words: lateral habenular nucleus, spatial learning and memory, Parkinson’s disease, Morris water maze

CLC Number:

R338.8

Lingna HAN,Chunlei WANG,Yongli CHANG,Li YUAN,Xiaojing LIU. Effect of electrical lesions of lateral habenular nucleus on spatial learning and memory functions in rats with Parkinson’s disease and its mechanism[J].Journal of Jilin University(Medicine Edition), 2021, 47(5): 1108-1115.

Figures/Tables 5

Tab. 1

Tab. 2

Fig. 1

Tab. 3

Fig. 2

References 27

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Group	Number of crossed squares	Number of rearings
Control	74.70±9.39	18.90±2.54
PD	37.00±5.42*	9.20±1.15*
PD+LHb lesion	34.00±6.27	7.90±1.15

Group	Distance to find thidden platform (l/cm)					Percentage of swimming distance in target quadrant （η/%）
Group	(t/d) 1	2	3	4	5	Percentage of swimming distance in target quadrant （η/%）
Control	1 770.34±104.99	784.44±54.70	497.88±36.59	268.04±34.08	189.70±26.83	57.70±4.40
PD	1 915.47±121.33	1 159.97±52.89^**	784.37±54.37^**	513.95±33.70^**	373.79±40.18^**	42.64±4.18^*
PD+LHb lesion	1 843.32±77.28	1 670 .01±87.40^△△	1 123.77±99.67^△△	956.47±66.03^△△	643.79±49.17^△△	26.65±3.97^△

Group	Level of 5-HT
Group	mPFC	Hippocampus
Control	641.44±73.87	500.45±41.80
PD	492.50±25.27	450.57±49.89
PD+LHb lesion	269.55±34.47*	214.24±27.55*

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Effect of electrical lesions of lateral habenular nucleus on spatial learning and memory functions in rats with Parkinson’s disease and its mechanism

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