ABSTRACT
Objective: To observe the effect of extracts from Ginseng Radix et Rhizoma,Anemarrhenae Rhizoma and Paeoniae Radix Rubra on N-methyl-D-aspartate receptors(NMDAR1) in hippocampal neurons in rats with vascular dementia and investigate its possible mechanism. Method: The 60 SPF male rats were randomly divided into normal group, sham-operated group,model group, traditional Chinese medicine group(0.20 g·kg-1)and memantine group(2.1 mg·kg-1),with 12 rats in each group. The model was established by repeated ischemia-reperfusion combined with intraperitoneal injection of sodium nitroprusside. After modelling, normal group, sham-operated group and model group were dosed the similar volume of normal saline once a day for 14 days. The learning and memory capacity was assessed by Morris water maze; pathologic change in the CA1 district of hippocampus was assessed by hematoxylin-eosin (HE) staining, and the expression level of NMDAR1 in hippocampal neuron membrane protein was detected by Western blot and immunohistochemistry(IHC),the NMDAR1 mRNA in hippocampal tissue was detected by Real-time PCR. Result:Compared with normal and sham-operated group, the latency period was prolonged in model group(PPPPPPPPConclusion:The extracts from Ginseng Radix et Rhizoma,Anemarrhenae Rhizoma and Paeoniae Radix Rubra can improve the learning and memory capacity of rats with vascular dementia, and alleviate the injury in CA1 district of hippocampus. The mechanism may be related to the down-regulation of NMDAR1 expression in hippocampal neurons.
ABSTRACT
In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P < 0.05), and in the double centralregions, right temporal region and right parietal region distinct fall (P < 0.01); (2) in the right temporal region of depression patients group the serotonin rise (P < 0.05); (3) in the right central region, left parietal region of depression patients group the acetylcholine fall (P < 0.05), left rear temporal region fall obviously (P < 0.01). The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P < 0.01)/(depression patients group:the range of [r] is [0.88, 0.94], P < 0.01); acetylcholine and norepinephrine, in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of [r] is [0.39, 0.76], P < 0.01 or P < 0.05)/(depression patients group: the range of [Ir] is [0.56, 0.64], P < 0.01); depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P < 0.01)/(depression patients group: the range of [r] is [0.68, 0.78], P < 0.01). (2) The two neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation. Serotonin and excited neurotransmitters are characterizeed by weak negative correlation (ordinary person group: in the right central region, left parietal region, double front temporal regions, right rear temporal region, the range of [r] is [0.25, 0.50], P < 0.01 or P < 0.05)/(depression patients group: in the whole encephalic regions, double parietal regions, double occipital regions, right front temporal region, left central region, left frontal region, the range of [r] is [0.18, 0.37], P < 0.01 or P < 0.05); acetylcholine and depression, neurotransmitters are characterized by weak negative correlation (ordinary person group: in the double frontal regions, left parietal region, left front temporal region, right rear temporal region, the range of [r] is [0.31, 0.46], P < 0.01 or P < 0.05)/(depression patients group: in double rear temporal regions, right front temporal region, double occipital regions, left central region, the range of [r] is [0.20, 0.32] , P < 0.01 or P < 0.05); do-pamine and depression neurotransmitters are characterized by weak middle negative correlation (ordinary person group: in left parietal region, right central region, left frontal region, left occipital region, double front temporal regions, the range of [r] is [0.33, 0.68], P < 0.01 or P < 0.05)/(depression patients group: in the whole region and other various regions except the left frontal region, right central region, the range of Irl is [0.21, 0.34], P < 0.01 or P < 0.05). Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions. Dopamine and acetylcholine are characterized by weak positive correlation (ordinary person group: in left frontal region, right parietal region, left front temporal region and left rear temporal region, the range of [r] is [0.37, 0.46], P < 0.01)/(depression patients group: in the whole region and the orther various regions except the double central regions, the range of [r] is [0.23, 0.5], P < 0.01 or P < 0.05); norepinephrine and serotonin are characterized by weak positive correlation (ordinary person group: in double front temporal regions, double rear temporal regions, right frontal region and left parietal region, the range of [r] is [0.34, 0.48], P < 0.01 or P < 0.05)/(depression patients group: in the whole and various regions, the range of [r] is [0.18, 0.42], P < 0.01). The main differences between the depression patients group and ordinary person group are: (1) In the whole regin, left frontal region and right central region of depression patients group, the six neurotransmitters all fall normally (P < 0.05). (2) The percent of dopamine falling or including dopamine falling, or including dopamine falling and serotonin rising in depression patients group increases. The percent of dopamine falling or including dopamine falling in the whole region, right frontal region, right central region increases (P < 0.01), such as dopamine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. (3) The percent of acetylcholine falling, or including acetylcholine falling, or including acetylcholine falling and neurotransmitters (beta)-receptor)rising in depression patients group increases. The percent of acetylcholine falling, or including acetylcholine falling in the right temporal region, double central regions increases (P < 0.05 or P < 0.01), such as acetylcholine decreasing, acetylcholine decreasing neurotransmitters increaseng, acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal, the synchronous change of multi-neurotransmitters has some certain regularities, which are not the simple linear relation. It's conformed that the three antagonizing pairs, neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group, are both characterized by strong antagonizing relation, that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation, prompt maybe has the indirect causal relationship. And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex. It's conformed preliminarily that the right frontal region and right central region are characterized by dopamine decreasing, acetylcholine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing, acetylchoine decreasing neurotransmitters increasing, acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on. Contrasted with the ordinary person group, the depression patients group have the notable difference.