Psychiatric morbidity with focus on obsessive–compulsive disorder in an Israeli cohort of adolescents with mild to moderate mental retardation

The study evaluated the prevalence of DSM-IV-TR-defined psychiatric disorders in adolescents with mental retardation, with a focus on obsessive-compulsive disorder (OCD), for which data at present are sparse. Eighty-seven adolescents with mild to moderate mental retardation attending the Israeli special-education system were screened for psychiatric disorders in general and obsessive-compulsive symptoms in particular. Sixty-one percent had at least one psychiatric disorder. Of the 13 participants receiving antipsychotic medication, none had an underlying psychotic disorder and most had anxiety or depressive disorders. OCD was detected in 11% of participants and was characterized by high rates of psychiatric comorbidities. The severity of autistic symptoms predicted 39% of the variance in the severity of OCD symptoms. Adolescents with mild to moderate mental retardation have high rates of psychiatric morbidities that are often inappropriately treated. OCD is prevalent in this population and is strongly associated with autistic symptoms. Further studies are required in adolescents with mental retardation to better delineate psychiatric morbidities and their appropriate treatment in this at-risk population.     

Effects of APOE ε2 allele on basal forebrain functional connectivity in mild cognitive impairment

Background

Basal forebrain cholinergic system (BFCS) dysfunction is associated with cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Apolipoprotein E (APOE) ε2 is a protective genetic factor in AD and MCI, and cholinergic sprouting depends on APOE.

Objective

We investigated the effect of the APOE ε2 allele on BFCS functional connectivity (FC) in cognitively normal (CN) subjects and MCI patients.

Method

We included 60 MCI patients with APOE ε3/ε3, 18 MCI patients with APOE ε2/ε3, 73 CN subjects with APOE ε3/ε3, and 36 CN subjects with APOE ε2/ε3 genotypes who had resting-state functional magnetic resonance imaging data from the Alzheimer's disease Neuroimaging Initiative. We used BFCS subregions (Ch1-3 and Ch4) as seeds and calculated the FC with other brain areas. Using a mixed-effect analysis, we explored the interaction effects of APOE ε2 allele × cognitive status on BFCS-FC. Furthermore, we examined the relationships between imaging metrics, cognitive abilities, and AD pathology markers, controlling for sex, age, and education as covariates.

Results

An interaction effect on functional connectivity was found between the right Ch4 (RCh4) and left insula (p < 0.05, corrected), and between the RCh4 and left Rolandic operculum (p < 0.05, corrected). Among all subjects and APOE ε2 carriers, RCh4-left Insula FC was associated with early tau deposition. Furthermore, no correlation was found between imaging metrics and amyloid burden. Among all subjects and APOE ε2 carriers, FC metrics were associated with cognitive performance.

Conclusion

The APOE ε2 genotype may play a protective role during BFCS degeneration in MCI.     

Unexpected toxicity of very low dose MPTP in mice: A clue to the etiology of Parkinson's disease?

Although much progress have been made in recent years, the etiology of idiopathic Parkinson's disease remains obscure. The chance discovery that injection of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induces a syndrome very similar to parkinsonism introduced the "environmental toxin" hypothesis but no toxin was ever found in any quantity in patients' brains. We have unexpectedly now found, however, that, in mice, very low doses of MPTP induce as much dopaminergic neuronal death as far higher doses. Cellular detoxification mechanisms would appear to be incapacitated at such low doses. This could infer that the barely discernible presence of an unidentified neurotoxin may be responsible for the onset of Parkinson's disease. Synapse 70:49–51, 2016 . © 2015 Wiley Periodicals, Inc.     

Awareness of cognitive deficits and clinical competence in mild to moderate Alzheimer’s disease: their relevance in clinical practice

Awareness of cognitive deficits and clinical competence were investigated in 79 mild to moderate Alzheimer’s disease patients. Awareness was assessed by the anosognosia questionnaire for dementia, and clinical competence by specific neuropsychological tests such as trail making test-A, Babcock story recall test, semantic and phonemic verbal fluency. The findings show that 66 % of the patients were aware of memory deficits, while the 34 % were unaware. Deficit in awareness correlated with lower scores on the Mini Mental State Examination test that, in the score range from 24.51 to 30 and from 19.50 to 24.50, appeared to be a significant predictor of level of awareness. None of the AD patients had fully preserved clinical competence, only 7 patients (9 %) had partially preserved clinical competence and 72 patients (91 %) had completely lost clinical competence. All the patients with partially preserved clinical competence (9 %) were aware of their memory deficit. The study indicates that neuropsychological tests used for the assessment of executive functions are not suitable for investigating clinical competence. Therefore, additional and specific tools for the evaluation of clinical competence are necessary. Indeed, these might allow clinicians to identify AD patients who, despite their deficits in selected functions, retain their autonomy of choice as well as recognize those patients who should proceed to the nomination of a legal representative.     

Effects of triptolide on degeneration of dendritic spines induced by Aβ1–40 injection in rat hippocampus

Although the exact cause of Alzheimer’s disease (AD) remains elusive, mounting evidence continues to support the involvement of neuroinflammation in the development of AD. Triptolide isolated from the herb Tripterygium wilfordii Hook F has anti-inflammatory and immunosuppressive activities. In this study, we observed the effects of triptolide on dendritic spines of hippocampal neurons in model rats with AD. Thirty male SD rats were randomly divided into control group, AD model group and triptolide-treated group. The AD model group was made with bilateral microinjection of aggregated beta-amyloid protein (Aβ)_1–40 into hippocampus in rats and the control group rats were injected with normal saline in the same way. The triptolide-treated group rats were administered triptolide intraperitoneally for 30 days after microinjection of aggregated Aβ_1–40 into hippocampus. Dendritic morphology of hippocampal neurons in each group was analyzed using Golgi staining and ImageJ software. Our data showed that the total number of intersection points of dendrites and spine density in hippocampal neurons in the AD model group were decreased as compared with the control group. However, the total number of intersection points of dendrites and spine density in hippocampal neurons in the triptolide-treated group were increased as compared with the AD model group. Our results indicate that triptolide can alleviate the degeneration of dendritic spines in hippocampal neurons in model rats with AD.     

Benefits of combined cholinesterase inhibitor and memantine treatment in moderate–severe Alzheimer's disease

BackgroundClinical studies and post hoc analyses have investigated the use of combination therapy for the treatment of Alzheimer's disease (AD). We review the evidence for the short- and long-term efficacy of combination therapy in AD.MethodsThe review is based on a search of the PubMed database to identify relevant articles concerning combination treatment with memantine and cholinesterase inhibitors (ChEIs).ResultsIn patients with moderate-to-severe AD, combination treatment with the N-methyl-d-aspartate receptor antagonist memantine and the ChEI donepezil has produced significant benefits in cognition, function, behavior, global outcome, and care dependency, compared with donepezil treatment alone. Data from long-term observational studies support these findings. Compared with ChEI monotherapy, combination treatment slowed cognitive and functional decline (a 4-year sustained effect that appeared to increase over time) and reduced the risk of nursing home admission. Preclinically, the combination of N-methyl-d-aspartate receptor modulation and acetylcholinesterase inhibition has been shown to act synergistically, which may explain the observed clinical effects of combination treatment.ConclusionTreatment with memantine/ChEI combination therapy in moderate-to-severe AD produces consistent benefits that appear to increase over time, and that are beyond those of ChEI treatment alone.     

Effects of cannabinoid CB₁ receptor antagonist rimonabant on acquisition and reinstatement of psychostimulant reward memory in mice

Drug addiction processes are considered to be mainly controlled by the mesocorticolimbic dopamine system. Cannabinoids, a class of psychoactive drugs of abuse, elicit their rewarding and pharmacological effects through the endocannabinoid system. Previous research has indicated that dopaminergic neurons in the mesocorticolimbic system are also under the control of the endocannabinoid system. Recently, evidence has suggested that the endocannabinoid system may also participate in the modulation of the common reward system. The present study examined whether rimonabant, a cannabinoid CB? receptor antagonist, disrupts the acquisition and reinstatement of psychostimulant reward memory measured by conditioned place preference (CPP). Mice were trained to acquire methamphetamine or cocaine-induced CPP. A priming injection of methamphetamine (0.5 mg/kg, i.p.) or cocaine (5 mg/kg, i.p.) was respectively given to reinstate methamphetamine or cocaine-induced CPP after extinction. Vehicle or rimonabant (1 or 3 mg/kg, i.p.) was administered at different time-points: 30 min before each CPP training session (acquisition) or 30 min before the priming injection (reinstatement). Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the acquisition of methamphetamine- and cocaine-induced CPP. At the high dose (3 mg/kg), rimonabant disrupted the reinstatement of extinguished methamphetamine- or cocaine-induced CPP. These findings indicate that cannabinoid CB? receptors play a major role in psychostimulant reward memory, and rimonabant may be a potential pharmacotherapy for psychostimulant addiction.     

Measuring awareness in people with mild to moderate Alzheimer's disease: Development of the Memory Awareness Rating Scale–adjusted

Variations in level of awareness among people with Alzheimer's disease (AD) may impact on well-being for the person with dementia and their carer, and may influence outcomes of cognitive rehabilitation interventions. Awareness has often been assessed using discrepancies between self and proxy rating or between self-rating and objective task performance, with the latter considered to be preferable. Measures are available that are suitable for people with mild AD, for example the Memory Awareness Rating Scale (MARS). However, these may be less appropriate for people whose impairments are more advanced and who consequently have more difficulty with the objective task component. In order to provide a measure suitable for people with moderate AD, an adjusted Memory Awareness Rating Scale (MARSA) was developed by altering the objective task component of the MARS. The MARSA was piloted with 41 participants with mild to moderate AD. It was found to be suitable for use with a broader group of participants than the MARS. The component ratings were found to have good internal consistency. The component ratings and the two indices of awareness had high test-retest reliability. The extension of the original measure offers the opportunity to consider awareness throughout the course of the disease and provides a basis for longitudinal investigations of awareness.     

Dopamine-depletion and increased α-synuclein load induce degeneration of cortical cholinergic fibers in mice

Cognitive dysfunction can be common among Parkinson's disease (PD) patients, and multiplication of the gene α-synuclein (αsyn) increases the risk of dementia. Here, we studied the role of dopamine-depletion and increased αsyn load and aggregation on cholinergic structures in vivo. Wild-type (WT) and mice with A30P αsyn overexpression were treated subacutely with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the number of cholinergic cells in their nucleus basalis magnocellularis-substantia innominata (NBM-SI), their cortical fiber density and their expression of different genes 1day or 90 days after the last MPTP-injection were measured. Long-term dopamine depletion decreased the expression of choline acetyl transferase (ChAT) in the NBM-SI of WT mice, but no neuron loss was observed. In contrast, cortical cholinergic fiber density was decreased three months after MPTP-injection. Increased brain-derived neurotrophic factor expression could maintain cholinergic functions under these conditions. Expression of A30P αsyn in six-months-old transgenic mice resulted in decreased tyrosine receptor kinase B expression, and lower cortical cholinergic fiber density. Dopamine-depletion by MPTP induced cholinergic cell loss in the NBM-SI and increased cortical fiber loss. Our findings may explain why cholinergic cells are more vulnerable in PD, leading to an increased probability of dementia.     

Continuous subcutaneous apomorphine infusion does not impair the dynamics of cognitive action control in mild to moderate Parkinson’s disease

Introduction

Continuous subcutaneous apomorphine infusion (CSAI) is increasingly used in Parkinson’s disease (PD), notably in patients contraindicated for subthalamic deep brain stimulation. Although it has been suggested that CSAI is safe regarding cognition, few studies have actually investigated its effect, especially on cognitive control which is a crucial process for goal-directed behavior. More specifically, its impact on the dynamics of cognitive action control, as reflected by the activation and suppression of impulsive responses, has yet to be investigated, which is the objective of the present study.

Methods

We compared cognitive action control between baseline (M0) and 6 months (M6) after the start of add-on CSAI by administering an oculomotor Simon task to 20 patients with mild to moderate PD. We used the activation–suppression model to determine whether CSAI had an effect on either the impulsive errors made in conflict situations or the suppression of these responses.

Results

We found no difference between M0 and M6 in the congruence effect regarding either reaction time or accuracy, indicating that overall conflict resolution was not influenced by CSAI. Furthermore, the rate of fast errors in the conflict situation and the last slope of the delta plots (reflecting the strength of impulsive response suppression) were unaffected by the treatment. The 95% confidence intervals calculated for the treatment effect on both of these measures fell below the range of usual meaningful effects.

Conclusion

We found no difference between M0 and M6, which strongly suggests that CSAI does not impair the dynamics of cognitive action control.

     

Interferon β1a (Avonex®) treatment in multiple sclerosis: similarity of effect on progression of disability in patients with mild and moderate disability

Objective To compare clinical responses to once-weekly intramuscular interferon-β-1 a [IFNβ-1 a, Avonex^®, Biogen] in multiple sclerosis (MS) patients with baseline Expanded Disability Status Scale (EDSS) ≤ 3.5 or > 3.5. Methods Patients with relapsing-remitting MS (RRMS), 124 with baseline EDSS ≥ 3.5 and 64 RRMS patients with EDSS > 3.5, were consecutively recruited to receive IFNβ-1 a 30 μg as a once weekly injection for 18 months. The primary endpoint of the study was the number of patients in each group with sustained worsening in disability, defined as 1-point deterioration in EDSS that persisted for at least 6 months during the 18 month follow-up period. Subordinate endpoints included relapse rates and the number of treatment dropouts. Results Among patients with baseline EDSS ≤ 3.5, 16.9 % experienced a deterioration in EDSS of at least 1 point ; 22.5 % experienced a deterioration of at least 0.5 %. Corresponding rates in patients with baseline EDSS > 3.5 were 23.4 % and 29 % respectively (no significant differences between patients stratified according to baseline EDSS status). The proportion of patients discontinuing therapy was significantly higher in patients with baseline EDSS > 3.5 than in those with baseline EDSS ≤ 3.5 (16/64 versus 12/124 ; p = 0.005). At the conclusion of follow-up, IFNβ-1 a therapy was associated with a 31.7 % reduction in relapse rate in patients with baseline EDSS ≤ 3.5 and a 37 % reduction in those with baseline EDSS > 3.5 (difference not significant). Conclusions During 18 months of treatment and follow-up, no difference was observed in clinical responses to IFNβ-1 a between RRMS patients with mild and moderate disability but discontinuation of therapy was more frequent in the more disabled group.     

Effects of extremely low frequency electromagnetic field (50 Hz) on pentylenetetrazol-induced seizures in mice

The electromagnetic fields (EMF) have various behavioral and biological effects on human body. There are growing concerns about the consequences of exposure to EMF. However, some studies have shown beneficial effects of these waves on human. In this paper, we study the effect of acute, sub acute and long-term exposure to 50 Hz, 0.1 mT magnetic fields (MF) on the seizure induction threshold in mice. 64 mice are used and divided into four groups. Eight mice in any group were selected to be exposed to MF for specific duration and the others were used as a control group. The duration of the applied exposures was as follows: (1) 1 day (acute), (2) 3 days (sub acute), (3) 2 weeks (sub acute), (4) 1 month (long term). The mice were exposed 2 h for a day. After exposure, the pentylentetrazol (PTZ) is injected to the mice to induce seizure and the needed dose for the seizure induction threshold is measured. In the acute exposure, the threshold to induce seizure in the exposed and sham-exposed groups was 44.25 and 46.5 mg, respectively, while the difference was not significant (p value = 0.5). In the sub acute exposure (3 days), the mean amount of drug to induce seizure was 47.38 mg in the exposed and 43.88 mg in the sham-exposed groups, however, the difference was not significant (p value = 0.3). The results were 52.38 and 46.75 mg after 2 weeks of exposure which were not significantly different either (p value = 0.2). After 1 month of exposure to MF, the threshold for the induction of seizure was significantly increased (p value < 0.05). The mean dosage to induce seizure in the exposed and control group was 54.3 and 45.75 mg, respectively. However, considering the p value, the difference in the seizure induction threshold between the exposed and sham-exposed groups after acute and sub acute exposure was not significant, analyzing the effects of acute, sub acute and long-term exposures totally indicates that increasing the exposure time increases the seizure induction threshold.     

Effect of intrathymic injection of allogene antigen on immune response to sciatic nerve transplantation in allogenic mice

BACKGROUND: The latest researches demonstrate that intrathymic injection of MHC antigen which reaches a certain dosage (2 mg, i.e., 4 × 108 cell extraction) can induce immunologic tolerance under non-antilymphocyte serum condition. OBJECTIVE: To investigate the effect of intrathymic injection of allogene antigen on survival and function of sciatic nerve in allogenic mice. DESIGN: Randomized controlled animal study. SETTING: The 4th Affiliated Hosptial of Harbin Medical University. MATERIALS: A total of 32 male donor C57BL/6(H-2b) mice of 4–8 weeks old and weighing 18–22 g and 44 female receptor Balb/c(H-2d) mice of 4–8 weeks old and weighing 18–22 g were selected from Heilongjing Veterinary Institution. The animal experiment had got confirmed consent from local ethic committee. METHODS: The experiment was carried out in the Laboratory (Provincial Key Laboratory) of the Fourth Hospital, Harbin Medical University from June 2006 to May 2007. C57BL/6(H-2b) mice were anesthetized to extract MHC (H-2b) antigen from splenic cells and sciatic nerves. Allogenous nerve transplantation group: Mice were given intrathymic injection of 100 μL saline; two weeks later, frozen sciatic nerves of donor mice were transplanted. Immunosuppressive agent group: Mice were given intrathymic injection of 100 μL saline; two weeks later, fresh sciatic nerves of donor mice were transplanted. At three days before transplantation, 10 mg/kg per day cyclosporin A was intraperitoneally injected once a day till mice were sacrificed. MHC (H-2b) antigen injection group: Mice were given intrathymic injection of MHC (H-2b) antigen from C57BL/6(H-2b) donor mice; two weeks later, fresh sciatic nerves of donor mice were transplanted. Autogenous nerve transplantation group: Mice were given intrathymic injection of 100 μL saline; two weeks later, fresh sciatic nerves were transplanted. MAIN OUTCOME MEASURES: ① Three weeks later, transplanted part of exposured sciatic nerve was used to measure the motor nerve conduction velocity. ② Transplanted nerve was stained with histochemical staining and observed light microscope and electron microscope. ③ Mice received mixed lymphocyte culture and delayed-typed hypersensitiveness to observe absorbency and measure depth of soles. RESULTS: All 76 mice were involved in the final analysis. ① Motor nerve conduction velocity: The nerve recovery in MHC (H-2b) antigen injection group was higher than that in allogenous nerve transplantation group, equal to immunosuppressive agent group and lower than autogenous nerve transplantation group. There were significant differences among them (P < 0.05). ② Histological changes of transplanted nerve: Light and electron microscopes demonstrated that there were a lot of regenerative nerve fibers in autogenous nerve transplantation group, immunosuppressive agent group and MHC (H-2b) antigen injection group, and all nerve fibers passed grafts. ③ Immunological examination: There was no significant difference in mixed lymphocyte culture among allogenous nerve transplantation group, autogenous nerve transplantation group and MHC (H-2b) antigen injection group (P < 0.05). Depth of soles in other groups was deeper than that in the MHC (H-2b) antigen injection group, and there was significant difference (P < 0.05); that was to say, delayed-typed hypersensitiveness was remarkable. CONCLUSION: The intrathymic injection of allogene MHC antigen may induce specific immune tolerance to allogenous sciatic nerve transplantation and promote nerve survival and functional recovery.     

Effects of happy and sad facial expressions on the perception of time in Parkinson’s disease patients with mild cognitive impairment

Introduction: Parkinson’s disease (PD) is a movement disorder caused by deterioration of the dopaminergic system. Previous studies have demonstrated temporal as well as emotional facial recognition impairment in PD patients. Moreover, it has been demonstrated that emotional facial expressions alter temporal judgments. In the present study, we investigate the magnitude of temporal distortions caused by the presentation of emotional facial expressions (happiness, sadness, and neutral) in PD patients with mild cognitive impairment (PD-MCI) and controls.

Method: Seventeen older adults with PD-MCI and 22 healthy older adults took part in the present study. Participants were tested with a time bisection task with standard intervals lasting 400 ms and 1600 ms. Moreover, a complete neuropsychological evaluation was conducted to characterize the sample.

Results: Differences between groups were observed indicating a general underestimation of time in PD-MCI patients. Temporal impairments in PD-MCI patients seem to be caused mainly by a dysfunction at the level of reference memory. The effect of emotional facial expressions on time perception was evident in both PD patients and controls, with an overestimation of perceived duration when happiness was presented and an underestimation when sadness was presented.

Conclusion: Overall, our results indicate that reduced cognitive abilities might be responsible for the lower temporal ability observed in PD-MCI patients. Moreover, similar effects of emotional stimuli were observed in both PD-MCI patients and controls.     

rnfluence of diet quantity on learning and memory ability 3nd immunological function in mice

BACKGROUND: Diet can regulate gene expression via manifesting genetic style so as to make a correlation with senility and tumor onset of tissue organs. OBJECTIVE: To observe the effect of diet quantity on learning and memory ability and immunological function changes in mice and verify the correlation between functional changes and diet quantity. DESIGN: Completely randomized grouping design. SETTINGS: Three Gorges University Medical College; School of Medicine, Hubei Institute for Nationalities. MATERIALS: Eighty Kunming mice of 3 weeks old, grade Ⅱ, weighing 17–18 g and either gender, were selected from Animal Experimental Center, Tongji Medical College, Huazhong University of Science and Technology. The experimental animals were disposed according to ethical criteria. At one week after feeding, they were randomly divided into 4 groups, including over-diet group, quantitative-diet group, quantitative-limit diet group and over-limit diet group with 20 mice in each group. METHODS: The experiment was carried out in the Medical Experimental Center of Hubei Institute for Nationalities and the Department of Laboratory, Central Hospital of Hubei Enshi Autonomous Prefecture from April to June 2006. ① Diet quantity of animals was > 6 g/d in the over-diet group, 4 g/d in the quantitative-diet group, 3.34 g/d in the quantitative-limit diet group and 1.8 g/d in the over-limit diet group, respectively. Mice in the four groups drank freely. ② At 35 days after feeding, every 10 mice were randomly selected from each group and enclosed in the wide mouthed bottle (250 mL, containing sodalime) to observe and record survival time under normal pressure and hypoxic condition. Other mice were given step down test, shuttle box test and autonomic activity test. Step down test: The first step-down latency and error times within 5 minutes were used to evaluate learning ability and the memory ability was retested at 24 hours later. Shuttle box test: The shuttle-box latency and error times within 5 minutes were used to evaluate learning ability and the memory ability was retested at 24 hours later. Times of autonomic activity within 5 minutes were used to evaluate ability of autonomic activity. In addition, blood was collected from eyeball to measure plasma immune globulin and complement by using immunoturbidimetry. MAIN OUTCOME MEASURES: ① Effect of different diet quantity on learning and memory ability; ② effect of different diet quantity on times of autonomic activity and survival time under hypoxia and normal pressure; ③ effect of different diet quantity on content of immune globulin and complement. RESULTS: All 80 mice were involved in the final analysis. ① Effect of different diet quantity on learning and memory ability: There was no significant difference in learning ability during step down test (P > 0.05). While, memory ability in the over-diet group and the quantitative-diet group was better than that in the over-limit diet group (t =2.235–2.423, P < 0.05). During shuttle box test, learning and memory ability in the over-diet group was superior to that in the over-limit diet group (t =2.237–2.431, P < 0.05). While, memory ability in the quantitative-diet group and quantitative-limit diet group was superior to that in the over-limit group (t =2.704–2.813, P < 0.05). ② Effect of different diet quantity on times of autonomic activity and survival time under hypoxia and normal pressure: There were significant differences in the times of autonomic activity among quantitative-diet group, quantitative-limit diet group and over-limit diet group (t = 2.725–2.98, P < 0.05). Survival time in the quantitative-diet group and the quantitative-limit diet group was longer than that in the over-diet group (t =2.365, 2.719, P < 0.05), but shorter than that in the over-limit diet group (t =2.427, 2.538, P < 0.05). While, survival time in the over-limit diet group was longer than that in the over-diet group (t =2.765, P < 0.01). ③ Effect of different diet quantity on content of immune globulin and complement: There was no significant difference in content of IgG and IgA (P > 0.05). Content of IgM in the over-limit diet group was higher than that in the over-diet group, quantitative-diet group and quantitative-limit diet group (t =2.304–2.421, P < 0.05). Contents of complement C3 and C4 in the quantitative-diet group and quantitative-limit diet group were higher than those in the over-diet group (t = 2.319–2.738, P < 0.05), but lower than those in the over-limit diet group (t =2.317–2.716, P < 0.05). While, contents of C3 and C4 in the over-limit diet group were higher than those in the over-diet group (t =3.247, 4.53, P < 0.01). CONCLUSION: Both quantitative diet and quantitative-limit diet can improve learning and memory ability, autonomic activity and immnological stress; however, over-limit diet may decrease these abilities.     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.     

Stabilisation of neurone number in the inferior olivary complex of aged ‘Purkinje cell degeneration’ mutant mice

Summary Virtually all cerebellar Purkinje cells degenerate in Purkinje cell degeneration (pcd) mutant mice between postnatal day (P) 17 and P45. The inferior olivary complex (IOC) in these mutants undergoes atrophy subsequent to the deprivation of its major cortical target; the number of IOC neurones declines by 18% by P23 and by 49% by P300. In the present study we used control (+/?) and mutant (pcd/pcd) mice that were 14–15 months old to determine whether any further cell loss is observed in the pcd IOC after P300. Nerve cell counts were obtained from serial paraffin sections of the medulla oblongata. The corrected estimate of neurone number in the left IOC of control mice was 12,785±794 cells (mean±SD, n=5); in pcd mutants that number was 6,722±535 (n=5). The 47% difference between control and mutant mice was highly significant (p<0.001). The perikarya of surviving IOC neurones were atrophic. Compared to P17 mutants, pcd homozygotes manifest a 50% cell loss by P428–P446, which does not practically differ from the deficit found on P300. These results suggest that, once a critical neuronal mass degenerates in the IOC of pcd mutants, the remaining neurones become stabilised and no further loss is observed even at an advanced age. The observation that only 50% of neurones degenerate, whereas the remaining 50% become atrophic in the IOC of pcd mutants, along with the fact that the pcd gene is known to be responsible for a 90%–99% loss of its primary CNS targets and not for cell atrophy, favour the contention that the IOC atrophy is transsynaptic. It is possible that surviving IOC neurones are sustained through synaptic connexions of climbing fibre collaterals with cortical interneurones or with neurones of the deep cerebellar nuclei or both.Supported in part by USPHS grant RO1-NS14426 (B.G.). Part of this work was presented at the 11th Annual Meeting of the European Neuroscience Association, 4–8 September 1988, Zürich, Switzerland     

Protective effects of （-）-epigallocatechin-3-gallate on D-galactose-induced neuronal apoptosis in mice

BACKGROUND： The neuroprotective effects of （-）-epigallocatechin-3-gallate （EGCG）, the main polyphenolic constituent of green tea, have been widely reported. However, the action mechanisms, in particular in D-galactose-induced aging mice, remain poorly understood. OBJECTIVE： The present study investigated the protective effects of EGCG on D-galactose-induced hippocampus neuronal apoptosis in aging mice, as well as the relationship with expression of p751CD, JNK2, and p53 proteins. DESIGN, TIME AND SETTING： A randomized, controlled, molecular biological, animal experiment was performed at the Laboratory of Pharmacology, Pharmaceutical College of China Medical University, China, from September 2006 to July 2008. MATERIALS： D-galactose and EGCG （Sigma, USA）, as well as terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling （TUNEL） In Situ Cell Apoptosis Detection Kit （Promega, USA）, were used in this study. METHODS： A total of 64 mice were equally and randomly divided into D-galactose model, low-dose EGCG, high-dose EGCG, and control groups. Mice in the D-galactose model, low-dose EGCG, and high-dose EGCG groups were subcutaneously injected with 3% D-galactose （150 mg/kg）, daily for 6 weeks, to establish a mouse model of aging. Mice in the control group were treated with saline （5 mL/kg）. At 3 weeks following injection, mice in the low-dose EGCG and high-dose EGCG groups were orally administered EGCG at a dose of 2 mg/kg and 6 mg/kg, respectively, once a day, for 4 consecutive days. Mice in the control and D-galactose model groups received distilled water （5 mL/kg）. MAIN OUTCOME MEASURES： Memory function was evaluated using a step-through passive avoidance test. Neuronal apoptosis in the mouse hippocampus was detected using TUNEL staining. Expression levels of the intracellular domain of the p75 neurotrophin receptor （p75NTR）-p751CD, JNK2, and p53 proteins in the hippocampus were determined using Western blot analysis. RESULTS： The aging mouse model was induced by subcutaneous injection of D-galactose, which resulted in obvious memory impairment, increased apoptotic index, and increased protein expression levels of p751CD, JNK2, and p53 in the hippocampus, compared with control mice （P 〈 0.01）. Oral EGCG administration （2 or 6 mg/kg） for 4 weeks significantly improved levels of memory deficit in the aging mice and reduced apoptotic indices and protein expression levels of p751CD, JNK2, and p53 in the mouse hippocampus （P 〈 0.01）. CONCLUSION： Results from this study demonstrated increased protein expression levels of p751CD, JNK2, and p53, as well as increased hippocampal neuronal apoptosis in a D-galactose-induced mouse model of aging. EGCG provided protective effects against D-galactose-induced neuronal apoptosis in the hippocampus by reducing protein expression levels of p751CD, JNK2, and p53 proteins in the hippocampus of aging mice.