Increase In Choline Acetyltransferase Activity Research Articles

Preventing Dementia Using Saffron, The Kampo Medicine, Kamiuntanto, and Their Combination, Kamiuntantokabankoka.

The objective of this review is to evaluate the anti-dementia activities of saffron and its combination with Kampo medicine. The Kampo formula Kamiuntanto composed of 13 crude drugs is well known for its anti-dementia activity. A significant increase in choline acetyltransferase activity and mRNA levels were observed. Polygala radix was identified as the most essential component drug in Kamiuntanto, probably due to the saponins, tenuifolin, and sinapinic acid. Ginseng was also identified as an essential Kamiuntanto component in terms of its synergistic functions with Polygala radix. Saffron, which was recommended in the Bencao Gangmu for memory and dementia, and is used as an anti-spasmodic, anti-catarrhal, and sedative herbal drug. Saffron and its major constituent, crocin were shown to enhance learning-memory, non-rapid eye movement (rem) sleep, and inhibit depression and neuronal cell death due to strong anti-oxidant and anti-inflammation activities. In addition based on the epidemiological studies such as the treatment of sleeping disorders and the clinical trials of saffron for Alzheimer patients, we demonstrated the indirect and direct anti-dementia activities of crocin and saffron.

Liraglutide inhibits the progression of prediabetes in rats by reducing Raf-1 kinase inhibitor protein.

BackgroundThe cleavage product of Raf-1 kinase inhibitor protein (RKIP), hippocampal cholinergic neurostimulating peptide (HCNP) is involved in the promotion of insulin secretion. Studies have shown that liraglutide can inhibit the progression of prediabetes. This study aims to investigate whether the above effects of liraglutide are related to RKIP and HCNP.MethodsInsulin-1 (INS-1) cells were divided into control group (CON), HCNP group, and HCNP + darifenacin group (H-DAR). The three groups were cultured with Roswell Park Memorial Institute (RPMI) 1640, synthetic HCNP (50 pg/mL) and RPMI 1640, and HCNP + RPMI 1640 + darifenacin respectively. Subsequently, twelve 12- to 14-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomly divided into 2 groups: the placebo group (PBO) and the liraglutide treatment group (LIRA). Six Long Evans Tokushima Otsuka (LETO) rats were used as the control group (CON). The LIRA group was given liraglutide 200 µg/kg intraperitoneally twice a day. After 12 weeks, body weight, fasting blood glucose, 2 hours postprandial blood glucose, and insulin resistance index were recorded. Western blot was used to detect expression level of C-RKIP, N-RKIP, and extracellular signal-regulated kinase of phosphorylation (p-ERK). Real-time quantitative polymerase chain reaction (qRT-PCR) to detect pancreatic tissue choline acetyltransferase (ChAT) and M3 cholinergic receptor (M3R) gene expression levels.ResultsAt glucose concentrations of 5.6 and 16.7 mmol/L, the insulin content in the HCNP group was higher than that in the CON and H-DAR groups (all P<0.01). The body weight and fasting serum insulin (FINS) of rats in the PBO group were higher than those in the LIRA group and the CON group (P<0.01). The relative content of C-RKIP protein in the PBO group was higher than that in the LIRA and CON groups (P<0.01). The relative content of N-RKIP protein and p-ERK protein was lower than that in the LIRA and CON group (P<0.05 and P<0.01, respectively). ChAT and M3R gene expression levels in PBO group were lower than those in LIRA and CON group (P<0.01).ConclusionsLiraglutide promotes the production of HCNP, can increase ChAT activity, activate M3R, and further promote the secretion of insulin.

Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection.

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

Walnut Oil Prevents Scopolamine-Induced Memory Dysfunction in a Mouse Model.

For thousands of years, it has been widely believed that walnut is a kind of nut that has benefits for the human body. Walnut oil, accounting for about 70% of walnut, mainly consists of polyunsaturated fatty acids. To investigate the effect of walnut oil on memory impairment in mice, scopolamine (3 mg/kg body weight/d) was used to establish the animal model during Morris Water Maze (MWM) tests. Walnut oil was administrated orally at 10 mL/kg body weight/d for 8 consecutive weeks. The results showed that walnut oil treatment ameliorated the behavior of the memory-impaired mice in the MWM test. Additionally, walnut oil obviously inhibited acetylcholinesterase activity (1.26 ± 0.12 U/mg prot) (p = 0.013) and increased choline acetyltransferase activity (129.75 ± 6.76 U/mg tissue wet weight) in the brains of scopolamine-treated mice (p = 0.024), suggesting that walnut oil could prevent cholinergic function damage in mice brains. Furthermore, walnut oil remarkably prevented the decrease in total superoxide dismutase activity (93.30 ± 5.50 U/mg prot) (p = 0.006) and glutathione content (110.45 ± 17.70 mg/g prot) (p = 0.047) and the increase of malondialdehyde content (13.79 ± 0.96 nmol/mg prot) (p = 0.001) in the brain of scopolamine-treated mice, indicating that walnut oil could inhibit oxidative stress in the brain of mice. Furthermore, walnut oil prevented histological changes of neurons in hippocampal CA1 and CA3 regions induced by scopolamine. These findings indicate that walnut oil could prevent memory impairment in mice, which might be a potential way for the prevention of memory dysfunctions.

Paternal Δ9-Tetrahydrocannabinol Exposure Prior to Mating Elicits Deficits in Cholinergic Synaptic Function in the Offspring.

Little attention has been paid to the potential impact of paternal marijuana use on offspring brain development. We administered Δ9-tetrahydrocannabinol (THC, 0, 2, or 4 mg/kg/day) to male rats for 28 days. Two days after the last THC treatment, the males were mated to drug-naïve females. We then assessed the impact on development of acetylcholine (ACh) systems in the offspring, encompassing the period from the onset of adolescence (postnatal day 30) through middle age (postnatal day 150), and including brain regions encompassing the majority of ACh terminals and cell bodies. Δ9-Tetrahydrocannabinol produced a dose-dependent deficit in hemicholinium-3 binding, an index of presynaptic ACh activity, superimposed on regionally selective increases in choline acetyltransferase activity, a biomarker for numbers of ACh terminals. The combined effects produced a persistent decrement in the hemicholinium-3/choline acetyltransferase ratio, an index of impulse activity per nerve terminal. At the low THC dose, the decreased presynaptic activity was partially compensated by upregulation of nicotinic ACh receptors, whereas at the high dose, receptors were subnormal, an effect that would exacerbate the presynaptic defect. Superimposed on these effects, either dose of THC also accelerated the age-related decline in nicotinic ACh receptors. Our studies provide evidence for adverse effects of paternal THC administration on neurodevelopment in the offspring and further demonstrate that adverse impacts of drug exposure on brain development are not limited to effects mediated by the embryonic or fetal chemical environment, but rather that vulnerability is engendered by exposures occurring prior to conception, involving the father as well as the mother.

Effect of Aged Garlic Ethyl Acetate Extract on Oxidative Stress and Cholinergic Function of Scopolamine-Induced Cognitive Impairment in Mice.

This study was performed to investigate the effect of aged black garlic ethyl acetate extract on scopolamine-induced cognitive impairment in mice. Aged garlic ethyl acetate extract (BG) was administrated at a dose of 25 or 50 mg/ kg in scopolamine-induced mice. Cognitive ability was evaluated using a Morris water maze test and a passive avoidance test. BGs (50 mg/kg) shortened the latency time that was increased by scopolamine and increased the platform crossing numbers that was significantly shortened by scopolamine after 5 days training in the Morris water maze test (P<0.05). BG (50 mg/kg) also significantly prolonged the latency time in the passive avoidance test (P<0.05). Result from biochemical analysis showed that BG increased levels of glutathione, glutathione peroxidase activity, and glutathione reductase activity, whereas BG significantly inhibited lipid peroxidation (P<0.05). BG also attenuated cholinergic degradation through inhibiting acetylcholinesterase activity and increasing choline acetyltransferase activity (P<0.05). In conclusion, BG protected against scopolamine-induced cognitive impairment through decreasing oxidative damage and regulating cholinergic function in the brains of mice. BG may therefore be a beneficial food for protecting against neurodegeneration such as Alzheimer’s disease.

Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aβ1-42 Induced Cognitive Deficit Mice.

Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer’s disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on β amyloid protein 1–42 (Aβ1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Aβ1-42 injection mice. JWKXS granules significantly decreased Aβ level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Aβ production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Aβ and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Aβ levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.

Effects of vitamin D3 supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy and independency in the elderly.1 Currently, no effective pharmacological interventions change the onset or progression of AD.2...

Ethanolic extract Ocimum sanctum. Enhances cognitive ability from young adulthood to middle aged mediated by increasing choline acetyl transferase activity in rat model

Patients with dementia are increasing steadily, cognitive impairment by dementia not only exclusively suffers by old people but also young to middle aged individuals. However, the mechanism of cognitive impairment occurs in young people is not understood. Further, current medication to impairment did not provide satisfactory results. Therefore, we investigated the potential role of Ocimum sanctum ethanolic extract to enhance cognitive ability in the rat in vivo model.Young to middle aged rats were divided into 3 groups (3, 6, 9 months old) were treated with (0, 50 and 100 mg/kg b.w.) O. sanctum for 45 days. We employed a behavioral assay to assess cognitive ability. Further, Nissl staining was performed to analyze hippocampus formation in dentate gyrus (DG), cornu ammonis 1 (CA1), cornu ammonis 3 (CA3). The expression and activity of ChAT in brain was analyzed by RT-PCR and ELISA. Our results showed that treatment of O. sanctum with a dosage of 100 mg/kg b.w. for 45 days induced the cognitive ability in nine months old rats. Further, we observed a significant increase in density of granular and pyramidal cells in DG, CA1, and CA3. These results were corroborated by an increase in the ChAT activity and gene expression in the rat model as well as HEK 293 cell culture model.Taken together, the administration of 100 mg/kg b.w. O.sanctum induced the expression of ChAT. The increased ChAT expression and activity may enhance the cognitive ability in 9 months old rats mimicking young and middle aged condition in humans.

Antioxidants Reverse the Changes in the Cholinergic System Caused by L-Tyrosine Administration in Rats.

Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in the activity of the enzyme tyrosine aminotransferase, leading to tyrosine accumulation in the body. Although the mechanisms involved are still poorly understood, several studies have showed that higher levels of tyrosine are related to oxidative stress and therefore may affect the cholinergic system. Thus, the aim of this study was to investigate the effects of chronic administration of L-tyrosine on choline acetyltransferase activity (ChAT) and acetylcholinesterase (AChE) in the brain of rats. Moreover, we also examined the effects of one antioxidant treatment (N-acetylcysteine (NAC) + deferoxamine (DFX)) on cholinergic system. Our results showed that the chronic administration of L-tyrosine decreases the ChAT activity in the cerebral cortex, while the AChE activity was increased in the hippocampus, striatum, and cerebral cortex. Moreover, we found that the antioxidant treatment was able to prevent the decrease in the ChAT activity in the cerebral cortex. However, the increase in AChE activity induced by L-tyrosine was partially prevented the in the hippocampus and striatum, but not in the cerebral cortex. Our results also showed no differences in the aversive and spatial memory after chronic administration of L-tyrosine. In conclusion, the results of this study demonstrated an increase in AChE activity in the hippocampus, striatum, and cerebral cortex and an increase of ChAT in the cerebral cortex, without cognitive impairment. Furthermore, the alterations in the cholinergic system were partially prevented by the co-administration of NAC and DFX. Thus, the restored central cholinergic system by antioxidant treatment further supports the view that oxidative stress may be involved in the pathophysiology of tyrosinemia type II.

Stolonidiol: Synthesis, Target Identification, and Mechanism for Choline Acetyltransferase Activation.

Stolonidiol, a marine natural product, has been reported to potentiate the activity of choline acetyltransferase (ChAT), the enzyme that produces the neurotransmitter acetylcholine. Here we report the total synthesis of stolonidiol starting from (R)-(+)-limonene. To identify the mechanism by which ChAT activity is increased, we sought to identify the biological target of stolonidiol. We show that stolonidiol binds to the phorbol ester binding site of protein kinase C (PKC), induces translocation of PKC to the cell membrane, and activates kinase activity. Furthermore, we confirmed the increase in ChAT activity observed upon treatment of cells with stolonidiol and show that this effect is mediated by PKC. Collectively, our data strongly suggest that PKC activation by stolonidiol is responsible for the resulting potentiation of ChAT activity.

CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway

Background: CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression. Methods: Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase. Results: Here we demonstrated, in the rat pheochromocytoma cell line PC12 and in primary rat neuronal cultures, that CXCL12-evoked up-regulation of CHT1, VAChT and ChAT was mediated by Akt. Inhibition of Akt by the pharmacological inhibitor GSK690693 eliminated CXCL12-stimulated increases in cholinergic gene expression. Moreover, treatment with GSK690693 reversed CXCL12-evoked increases in choline acetyltransferase activity and ACh production. Conclusion: Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway.

When Mars Versus Venus is Not a Cliché: Gender Differences in the Neurobiology of Alzheimer's Disease.

OPINION article Front. Neurol., 12 January 2015Sec. Neurodegeneration https://doi.org/10.3389/fneur.2014.00288

Inhibiting β-amyloid-associated Alzheimer's pathogenesis in vitro and in vivo by a multifunctional dimeric bis(12)-hupyridone derived from its natural analogue.

Fibrillar aggregates of β-amyloid protein (Aβ) is the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit the formation of Aβ fibrils and block Aβ fibrils-associated toxicity may have therapeutic potential to combat AD. Bis(12)-hupyridone (B12H) is a multifunctional homodimer derived from huperzine A, which is an anti-AD drug in China. In the current study, the inhibitory effect of B12H on the formation of Aβ fibrils and their associated toxicity was investigated both in vitro and in vivo. By using Thioflavin T fluorescence assay, we found that B12H (0.3-3μM) directly inhibited Aβ fibrils formation following co-incubation of B12H and Aβ1-40 at 37°C for 6days in vitro. However, huperzine A, at the same concentrations, did not show significant inhibitory effect on Aβ1-40 fibrils formation. Moreover, B12H markedly reduced Aβ1-40-induced cytotoxicity in cultured SH-SY5Y cells, as evidenced by the increase in cell viability, the decrease in lactate dehydrogenase release, and the reduction of apoptotic nuclei. Most importantly, B12H (0.2 and 0.4mg/kg) reduced intracerebroventricular Aβ1-40 infusion-induced cognitive and memory impairments in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with increasing choline acetyltransferase activity and decreasing acetylcholinesterase activity. Collectively, our study provided novel sights into the potential application of B12H in AD treatment.

3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia.

3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study ligated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphthalide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby improving cerebral neuronal injury and cognitive deficits.

Effects of pregnenolone intervention on the cholinergic system and synaptic protein 1 in aged rats

Objective: To observe the effect of pregnenolone (PREG) intervention on the cholinergic system function and the synaptic protein 1 (SYP1) expression in different brain regions of aged rats. Method: Twenty-four-month-old male Sprague Dawley rats intraperitoneally injected every other day for one month were divided into blank control group, solvent control group, PREG (0.5 mg/kg) intervention group and PREG (2.0 mg/kg) intervention group. The rats were sacrificed 2 d after the intervention and the corresponding regions of brain tissue were separated and cryopreserved. Western blot analysis was used to detect the expression level of choline acetyltransferase (ChAT), SYP1, serum PREG and the activity of ChAT and acetylcholinesterase (AChE) in different brain regions. In addition, the semiquantitative changes in the expression level of ChAT and SYP1 in frontal lobe and hippocampus were tested by immunohistochemistry. Result: Western blot and immunohistochemistry analysis showed that PREG (2.0 mg/kg) administration led to a significant increase of ChAT and SYP1 expressions in frontal lobe, temporal lobe, and hippocampus regions (p < 0.05). The result of enzyme-linked immunosorbent assay showed that PREG (2.0 mg/kg) administration significantly increased ChAT activity and serum PREG levels and caused a decrease in AChE activity (p < 0.05); while PREG (0.5 mg/kg) only elevated levels of serum PREG. Conclusion: PREG significantly improved the synaptic plasticity of memory-related brain areas of aged rats, significantly increased brain cholinergic activity and thus helps to improve learning and memory in aged rats.

Maternal inflammation promotes fetal microglial activation and increased cholinergic expression in the fetal basal forebrain: role of interleukin-6

Perinatal exposure to infectious agents with associated maternal immune activation (MIA) leads to neuroanatomical and behavioral dysregulation reminiscent of autism spectrum disorders. Persistent microglial activation as well as increased choline acetyltransferase (ChAT) activity in the basal forebrain (BF) are characteristic of autistic subjects. Previous studies have shown that medium from activated microglia promotes cholinergic differentiation of precursors in the BF. We sought to determine whether MIA in vivo would lead to a similar effect on developing BF neurons. Pregnant mice were treated with the viral mimic polyinosinic-polycytidylic acid (poly(I:C)) or saline. Poly(I:C) treatment resulted in increased production of cytokines and chemokines in fetal microglia and increased ChAT activity and cholinergic cell number in the perinatal BF. Whether microglial activation causes these changes is unclear. Examination of fetal brains from mice lacking interleukin-6 (IL-6 KOs) revealed an elevation in non-microglial-derived cytokines and chemokines over wild-type controls. Moreover, IL-6 KO offspring showed an elevation of ChAT activity even in the absence of poly(I:C) administration. These data suggest that elevations in cytokines and/or chemokines caused either by maternal poly(I:C) administration or by the absence of IL-6 are associated with alterations in cholinergic development in the BF.

Upregulated acetylcholine synthesis during early differentiation in the embryonic stem cell line CGR8

Stem cells are used to generate differentiated somatic cells including neuronal cells. Synthesis and release of acetylcholine, a neurotransmitter and widely expressed signaling molecule, were investigated in the murine embryonic stem cell line CGR8 during early differentiation, i.e. in the presence of leukemia inhibitory factor (LIF) to maintain pluripotency and in the absence of LIF to induce early differentiation. CGR8 cells express choline acetyltransferase (ChAT) as demonstrated by measurement of enzyme activity and substantial inhibition by bromoacetylcholine. Pluripotent CGR8 cells showed a ChAT activity of 250pmol acetylcholine/mg/h, contained 1.1pmol acetylcholine/106cells and released about 12.00pmol acetylcholine/1x106cells/6h. Removal of LIF induced early differentiation as evidenced by reduced transcription factors Oct-4 and Nanog and a substantial slowing of the proliferation rate. Under this condition acetylcholine synthesis increased to 1640pmol/mg/h; related to the pluripotent state the content of acetylcholine increased 10-fold and the release to about 32pmol acetylcholine/1x106cells/6h. Enzyme kinetic analysis showed a significant increase of the Km for the precursor acetyl-CoA and of Vmax without a change of the Km for the precursor choline. In conclusion, early differentiation of the stem cell line CGR8 is associated with a substantial increase in ChAT activity and acetylcholine release.

Joint neurodevelopmental and behavioral effects of nonylphenol and estradiol on F1 male rats

The purpose of present study is to examine whether gestational exposure of two major environmental endocrine-disrupting chemicals, nonylphenol (NP) and estradiol (E2), would affect nervous system development of offspring rats and explore the joint effects of NP and E2. After impregnation, dams were assigned to seven groups. The first and second groups received gavage with NP at dose levels of 50 mg/kg/day (NP-L) and 100 mg/kg/day (NP-H); the third and fourth groups were gavaged with E2 at dose levels of 10 μg/kg/day (E2-L) and 20 μg/kg/day (E2-H); the fifth and sixth groups were gavaged with joint NP and E2 [NP 50 mg/kg/day + E2 10 μg/kg/day (NP–E2-L) and NP 100 mg/kg/day+E2 20 μg/kg/day (NP–E2-H)] dissolved in groundnut oil; and the seventh group was orally administered with groundnut oil alone (vehicle control; 2 ml/kg/day), respectively, daily from gestational days 9 to 15 (transplacental exposures). Compared to the control, exclusive NP and E2 treatment groups, joint exposure to NP–E2-L and NP–E2-H has both produced a significant decrease in mean litter size and number of live pups per litter in dams; Offspring rats spent more time to perform cliff-drop aversion reflex, surface righting reflex, air righting reflex, auditory startle, and visual placing; In Morris water maze task, an increased escape latency was presented in offspring rats; In step-down avoidance test, offspring rats jointly exposed to NP and E2 spent more reaction time. Decrease in acetylcholinesterase activity and increase in choline acetyltransferase activity were observed in the hippocampus of offspring rats. Gestational joint exposure to NP and E2 might induce nervous development impairment of offspring rats. Moreover, additive toxic effects of NP and E2 on nervous development have been identified among offspring rats as well.

Effect of Sailuotong capsule on intervening cognitive dysfunction of multi-infarct dementia in rats

To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.