Cholinergic Receptor Site Binding,Choline Acetyltransferase,and Acetylcholinesterase Activity in the Forebrain and Brainstem of the Dahl Rat Model of Essential Hypertension

Muscarinic and nicotinic receptor site binding and the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the forebrain and brainstem of Dahl salt-sensitive (DS) and salt-resistant (DR) rats was investigated. The DS line had a greater density of muscarinic sites in the cortex, hypothalamus, and medulla. Hypertensive DS rats had a greater density of sites than normotensive DS rats. ChAT activity was also higher in the cortex and hypothalamus of the DS line than the DR line. No significant differences were found in the activity of AChE or the concentration of nicotinic sites. These results suggest that the central muscarinic cholinergic system may participate in the pathogenesis of hypertension in the DS rat. The data indicate that central cholinergic activity is possibly greater in the DS than the DR rat and that this may help to explain the enhanced pressor response in the DS line after pharmacological activation of the central cholinergic system.     

Pre- and postsynaptic markers of cholinergic neurons in the cerebral cortex of rats of different ages

In order to investigate the effect of aging on postsynaptic muscarinic binding, we measured 3H-PZ binding in the cerebral cortex of male Fisher 344 rats of different ages. ChAT activity was measured as a presynaptic marker of the cholinergic system. Total and salt-soluble AChE activities were also measured. Maximal binding of 3H-PZ and ChAT activity did not change during aging. The ratio of detergent-soluble AChE to salt-soluble AChE was lower in 30-month-old rats than in 4-month-old rats. The results of the present study do not indicate that the amount of M1 muscarinic receptors proposed to be located postsynaptically decreases during aging. In senescent rats, however, the proportions of salt-soluble and detergent-soluble AChE may differ form those in young rats.     

Cardiac Acetylcholinesterase Molecular Forms and Choline Acetyltransferase in the Dahl (Salt-Sensitive) Hypertensive Strain of Rats: A Regional Study

A regional study of acetylcholinesterase (AChE) molecular forms and choline acetyltransferase (ChAT) in the hearts of Dahlsalt sensitive (DS) and salt resistant (DR) rats was performed in animals administered either 8% or 0.35% dietary NaCl. Atria isolated from DS rats, regardless of dietary NaCl intake, had lower activities of all of the AChE molecular forms and ChAT when compared to their dietary-matched DR controls. In the ventricles, the activities of AChE molecular forms and ChAT were lower in DS rats compared to dietary-matched DR rats only when 8% NaCl diets were administered. The percent contribution of each of the molecular forms to the total AChE pool was not affected by animal strain or diet.     

Maternal hypothyroxinemia disrupts neurotransmitter metabolic enzymes in developing brain.

Maternal thyroid status influences early brain development and, consequently, cognitive and motor function in humans and rats. The biochemical targets of maternal thyroid hormone (TH) action in fetal brain remain poorly defined. A partially thyroidectomized rat dam model was therefore used to investigate the influence of maternal hypothyroxinemia on the specific activities of cholinergic and monoaminergic neurotransmitter metabolic enzymes in the developing brain. Maternal hypothyroxinemia was associated with reduced monoamine oxidase (MAO) activity in fetal whole brain at 16 and 19 days gestation (dg). A similar trend was observed for choline acetyltransferase (ChAT) activity. In contrast, DOPA decarboxylase (DDC) activity was markedly elevated at 21 dg. Further study of these enzymes at 14 dg showed no differences between normal and experimental progeny - suggesting they become TH sensitive after this age. Tyrosine hydroxylase (TyrH) and acetylcholinesterase (AChE) activities were unaffected prenatally. During postnatal development, the activities of TyrH, MAO, DDC and, to a lesser extent, AChE were increased in a brain region- and age-specific manner in experimental progeny. The prenatal disturbances noted in this study may have wide-ranging consequences since they occur when neurotransmitters have putative neurotropic roles in brain development. Furthermore, the chronic disturbances in enzyme activity observed during postnatal life may affect neurotransmission, thereby contributing to the behavioural dysfunction seen in adult progeny of hypothyroxinemic dams.     

Myocardial Cholinergic Receptor Sites and Enzyme Activity in the Dahl Model of Essential Hypertension

The density of muscarinic receptor sites, choline acetyltransferase (ChAT), and aceytlcholinesterase (AChE) activity in the myocardium of the Dahl salt-sensitive (DS) and salt-resistant (DR) rat was investigated. Both normotensive and hypertensive (as a result of 8.0% NaCl added to the diet) DS rats displayed a lower concentration of muscarinic receptors and less ChAT and AChE activity in myocardial tissue than normotensive DR rats. Lower receptor site density and enzyme activity in the myocardial of the DS line may reflect decreased vagal tone. If true, this may produce deficits in the ability to appropriately adjust heart rate (HR) in response to elevations in blood pressure (BP). Therefore, the present results may be viewed as exacerbational factors in the pathogenesis of hypertension in the DS line.     

Age-related responses of the rat cerebral cortex: influence of vitamin E and exercise on the cholinergic system

In this study, we have assessed the impact of vitamin E and exercise on acquisition and retention of spatial memory for a given task in aging rats, using a T-maze. Acetylcholine esterase (AChE) and cholineacetyl transferase (ChAT) activities and acetylcholine (ACh) were measured in the cerebral cortex (CC) of male Wistar rats of 4- (adult), 12- (middle-aged) and 18-months (old) of age. Animals were categorized into sedentary [(SEC (N)], sedentary supplemented [SEC (+E)], swim trained [SWT (N)] and swim trained supplemented [SWT (+E)]. In the old, ChAT activity increased in the SEC (+E). AChE activity was highest in the adults, irrespective of training or supplementation. By contrast, ACh concentration remained unaltered with age, exercise and supplementation. Middle-aged and old rats were benefited in terms of a better acquisition and retention in the case of those that were trained and supplemented with Vitamin E. Adults showed better retention in all the groups after 7 and 15 days, while in the middle-aged, training was beneficial after 15 days. We observed decreased AChE activity when old rats were trained with the supplement. Our results also suggest that this regimen may be analogous to the AChE inhibitors that are widely advocated to derive positive benefits in up-regulating the possible reduction in ACh and in turn age-associated memory deficits.     

Effects of Acute and Chronic Ethanol and Dihydroergotoxine (Hydergine) on Neurotransmitter Enzymes in Brain

The effects of acute and chronic ethanol (ETOH) and dihydroerge toxine mesylate (DHET) alone or in combination on choline acetyl-transferase (ChAT), glutamic acid decarboxylase (GAD), acetylcho-linesterase (AChE), and acetylcoenzyme A hydrolase (AcCoA-H) were investigated in various brain regions of young adult male mice. Acute ETOH, an hour after a single dose of 2 g/Kg, did not affect these enzyme activities in any brain regions examined although it inhibited the locomotor activity of these animals. Acute DHET, an hour after a single dose of 2 mg/Kg, significantly increased (17%) ChAT activity in corpus striatum only and stimulated the locomotor activity of the mice. Acute ETOH + DHET had no effects on these enzymes either. Chronic ETOH significantly increased ChAT activity in cerebelium (45%), corpus striatum (21%), and hypothalamus (82%) but decreased the enzyme activity in hippocampus by 16%. Chronic DHET significantly increased ChAT activity in corpus striaturn (24%), hypothalamus (80%), and midbrain (16%), and significantly increased AChE in brainstem (20%) and corpus striatum (45%). Chronic ETOH + DHET significantly increased both ChAT (11%) and GAD (14%) activity only in corpus striatum. These results confirm the reported alterations of cholinergic and GABAnergic systems in brain after chronic administration of ethanol, and further support the morphologic changes observed in human mammillary body, corpus striatum, hippocampus, and cerebellum after chronic alcoholiam. In addition, these data also suggest that corpus striatum and hypothalamus are the brain areas most sensitive to chronic DHET exposure.     

胆碱能过活化状态下“疏肝调神”针法对CUMS抑郁大鼠行为学的影响

目的观察胆碱酯酶抑制剂毒扁豆碱所致的胆碱能过活化状态下,“疏肝调神”针法对慢性不可预知温和应激(CUMS)抑郁模型大鼠前额叶和血清胆碱能相关因子表达和行为学的影响,探讨“疏肝调神”针法治疗抑郁障碍的作用机制。方法采用雄性Sprague Dawley(SD)大鼠60只,随机分为正常组、模型组、电针组、东莨菪碱组(阳性药物组)、毒扁豆碱组(乙酰胆碱酯酶抑制剂组)和电针+毒扁豆碱组,除正常组外进行3 w的造模,成功造模后,予电针或药物干预,持续3 w,观察各组大鼠的体重及糖水偏好实验、强迫游泳实验和新环境抑制进食实验的行为学变化,并应用酶联免疫吸附试验(ELISA)检测前额叶乙酰胆碱酯酶(AChE)、乙酰转移酶(ChAT)、乙酰胆碱(ACh)、去甲肾上腺素(NE)和血清内皮质醇(CORT)的含量变化。结果与正常组比较,模型组大鼠的体重、糖水偏好率显著下降,累计不动时间和延迟进食时间显著延长,AChE、NE含量明显降低,ChAT、ACh、CORT含量明显升高;与模型组比较,电针组和东莨菪碱组大鼠抑郁样行为明显改善,电针组大鼠AChE、NE含量升高,ChAT、ACh、CORT含量明显降低,毒扁豆碱组大鼠抑郁样行为显著加重,AChE、NE含量明显降低,ChAT、ACh、CORT含量明显升高;与毒扁豆碱组比较,电针+毒扁豆碱组大鼠的抑郁样行为明显改善,AChE、NE含量升高,ChAT、ACh、CORT含量明显降低。结论电针可有效改善CUMS抑郁大鼠的抑郁样行为,其作用机制可能是电针参与调控胆碱能代谢,有效解除胆碱能过活化状态,降低机体对应激的易感性而发挥抗抑郁效应的。     

地黄益智方对Aβ1～40所致老年性痴呆模型大鼠学习记忆能力的影响

目的观察地黄益智方对Aβ1～40所致老年性痴呆模型大鼠学习记忆能力的影响。方法 120只SD雄性大鼠随机分为正常组,模型组,地黄益智方小、中、大剂量组,采用大鼠双侧海马CA1区注射Aβ1～40复制老年性痴呆模型,造模24 h后开始给药,连续4 w。分别在给药1、3 w后用Morris水迷宫法连续5 d进行定位航行实验,第6天进行空间探索实验,检测各组大鼠学习记忆能力;2、4 w用生化法检测各组大鼠大脑皮层ChAT、AChE的活性变化。结果模型组大鼠明显存在学习记忆功能障碍,其中1 w后第2、4、5、6天与空白组相比有差异(P=0.016、0.000、0.003、0.001),3 w后第1、4、5、6天与空白组相比有差异(P=0.023、0.006、0.005、0.007),地黄益智方各剂量组行为障碍明显轻于模型组。模型组ChAT活性明显降低,2、4 w时与空白组相比有差异(P=0.011、0.024);模型组AChE活性明显增高,2、4 w时与空白组相比有差异(P=0.003、0.010);地黄益智方各剂量组乙酰胆碱转移酶(ChAT)、乙酰胆碱酯酶(AChE)活性改变明显轻于模型组。结论地黄益智方能改善Aβ1～40所致老年性痴呆模型大鼠学习记忆能力,可能与其调节中枢神经递质ChAT、AChE活性有关。     

异菝葜皂甙元及多奈哌齐对大鼠脑神经营养因子和胆碱乙酰转移酶的影响

目的平行对比观察知母皂甙元25位异构体异菝葜皂甙元（SMI）与胆碱酯酶抑制剂多奈哌齐（DN）对自然衰老大鼠行为学及脑毒蕈碱样胆碱受体（M受体）、脑源性神经营养因子（BDNF）水平和胆碱乙酰转移酶（ChAT）阳性神经元的影响，探讨SMI的作用机制。方法20月龄SD大鼠随机分为老年对照组、SMI组、DN组及SMI＋DN合并用药组，另设SD青年对照组。30d、60d及90d后用Y型电迷路评价大鼠学习记忆能力，放射配给结合法测乙酰胆碱M受体密度，酶联免疫吸附方法测BDNF含量，Fonnun法测ChAT活性，免疫组化法测大鼠不同脑区ChAT阳性神经元密度。结果老年鼠和青年鼠比较，学习记忆能力、脑内乙酰胆碱M受体密度[（1144±124）fmol／mg蛋白和（907±109）fmol／mg蛋白]、BDNF水平[（2．17±0．15）pg／mg蛋白和（1．36±0．14）pg／mg蛋白]和ChAT活性[（16．38±3．06）nmol·h^-1·mg^-1和（6．29±1．94）nmol·h^-1·mg^-1]显著降低（P〈0．05，P〈0．01）。老年鼠喂服SMI后，上述各指标均有显著改善[（1029±107）fmol／mg蛋白、（1．69±0．15）pg／mg蛋白和（10．18±1．47）nmol·h^-1·mg^-1，P〈0．05，P〈0．01]。老年鼠喂服DN后，学习能力改善，但长期记忆能力改善不显著，脑乙酰胆碱M受体密度和BDNF含量无增加，ChAT活性增加[（10．18±1．47）nmol·h^-1·mg-1]。海马、基底前脑斜角带核和Meynert基底核的ChAT阳性神经元密度检测结果，老年鼠显著低于青年鼠，SMI使该3个脑区都显著增加，DN仅使海马增加。结论SMI与胆碱酯酶抑制剂的药理作用机制不相同。SMI长期疗效明显好于胆碱酯酶抑制剂，SMI能延缓神经退行性变化的进程，可能是它改善学习记忆功能的重要机制之一。     

Effect of treatment with the cholinesterase inhibitor rivastigmine on vesicular acetylcholine transporter and choline acetyltransferase in rat brain

A decline of cholinergic neurotransmission probably contributes to cognitive dysfunction occurring in Alzheimer's disease (AD) and vascular dementia (VaD). Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors are the only drugs authorized for symptomatic treatment of AD and are also under investigation for VaD. The present study has investigated the influence of two doses of the AChE inhibitor rivastigmine (0.625 mg/Kg/day and 2.5 mg/Kg/day) on vesicular acetylcholine transporter (VAChT) and on choline acetyltransferase (ChAT) expression in frontal cortex, hippocampus, striatum and cerebellum of normotensive and spontaneously hypertensive rats (SHR). Cholinergic markers were assessed by immunochemical (Western blotting) and immunohistochemical techniques. In frontal cortex and striatum of normotensive rats, treatment with the lower dose (0.625 mg/Kg/day) of rivastigmine had no effect on VAChT immunoreactivity and increased slightly ChAT protein immunoreactivity. The higher dose (2.5 mg/Kg/day) of the compound increased significantly VAChT and ChAT protein immunoreactivity. In hippocampus rivastigmine induced a concentration-dependent increase of VAChT protein expression and no significant changes of ChAT protein expression. A similar pattern of VAChT and ChAT protein expression was observed in control SHR, whereas treatment of SHR with rivastigmine induced a more pronounced increase of VAChT protein immunoreactivity in frontal cortex, hippocampus and striatum compared to normotensive rats. Our data showing an increase of VAChT after treatment with rivastgmine further support the notion of an enhancement of cholinergic neurotransmission by AChE/ChE inhibitors. The observation of a greater expression of this cholinergic marker in SHR suggest that AChE inhibition may provide beneficial effects on cholinergic neurotransmission in an animal model of VaD.     

Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with development of brain damage and dysfunction

In the present study we investigated the effect of the non-alcoholic fatty liver disease (NAFLD) on the alterations in the activity of neurotransmitters catabolizing enzymes and energy catabolising enzymes, prooxidants, endogenous antioxidants and proinflammatory cytokines in brain tissue of NAFLD rats. Rats were intraperitonealy injected with CCl4 solution at a dose of (0.021?mole/Kg, 20?μL, body weight) three times weekly for four weeks. Acetylcholine esterase (AChE), monoamine oxidase (MAO), prooxidant/ antioxidants status, ATPase, lipid profile and glucose level were estimated spectrophotometrically while inflammatory markers; interleukin 6 and tumor necrosis factor alpha (IL6 and TNF-α) and insulin were assessed by ELISA technique. Our results showed that the induced NAFLD and insulin resistance (IR) were accompanied with hyperglycemia and hyperlipidemia and lowered brain glucose level with elevated ATPase activity, prooxidant status (TBARS level, xanthine oxidase and cytochrome 2E1 activities), and inflammatory markers. Through the induction period AChE activity was significantly increased compared to control in blood, liver and brain tissues. Also, MAO activity was significantly increased in both brain and liver tissue but decreased in serum compared with control. These biochemical data were supported with pathophysiological analysis that showed severe neurodegeneration, pyknosis acuolations and cavitations. These observations warrant the reassessment of the conventional concept that the NAFLD with IR progression may induce disturbances in activities of neurotransmitters catabolising enzymes and energy production accompanied with oxidative stress and metabolic disorders, acting as relative risk factors for brain dysfunction and damage with the development of age-associated neurodegenerative diseases such as Alzheimer's disease.     

孕烯醇酮对老年大鼠记忆相关脑区胆碱乙酰转移酶表达的影响

目的观察孕烯醇酮对老年大鼠记忆相关脑区胆碱乙酰转移酶(ChAT)表达的影响。方法雄性老年大鼠40只,随机分为空白组、溶剂组、小剂量孕烯醇酮组、大剂量孕烯醇酮组,每组10只。隔日腹腔注射1个月,通过免疫组织化学技术分别检测各组大鼠额叶、颞叶、海马皮质区ChAT表达情况。结果与空白组比较,大剂量孕烯醇酮组大鼠额叶、颞叶、海马皮质区ChAT免疫阳性细胞明显增加,差异有统计学意义(P<0.05);而溶剂组和小剂量孕烯醇酮组ChAT阳性细胞数无明显增加,差异无统计学意义(P>0.05)。结论大剂量孕烯醇酮可以显著改善老年大鼠胆碱能系统活性。     

Effect of Treatment with the Cholinesterase Inhibitor Rivastigmine on Vesicular Acetylcholine Transporter and Choline Acetyltransferase in Rat Brain

A decline of cholinergic neurotransmission probably contributes to cognitive dysfunction occurring in Alzheimer's disease (AD) and vascular dementia (VaD). Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors are the only drugs authorized for symptomatic treatment of AD and are also under investigation for VaD. The present study has investigated the influence of two doses of the AChE inhibitor rivastigmine (0.625 mg/Kg/day and 2.5 mg/Kg/day) on vesicular acetylcholine transporter (VAChT) and on choline acetyltransferase (ChAT) expression in frontal cortex, hippocampus, striatum and cerebellum of normotensive and spontaneously hypertensive rats (SHR). Cholinergic markers were assessed by immunochemical (Western blotting) and immunohistochemical techniques. In frontal cortex and striatum of normotensive rats, treatment with the lower dose (0.625 mg/Kg/day) of rivastigmine had no effect on VAChT immunoreactivity and increased slightly ChAT protein immunoreactivity. The higher dose (2.5 mg/Kg/day) of the compound increased significantly VAChT and ChAT protein immunoreactivity. In hippocampus rivastigmine induced a concentration‐dependent increase of VAChT protein expression and no significant changes of ChAT protein expression. A similar pattern of VAChT and ChAT protein expression was observed in control SHR, whereas treatment of SHR with rivastigmine induced a more pronounced increase of VAChT protein immunoreactivity in frontal cortex, hippocampus and striatum compared to normotensive rats. Our data showing an increase of VAChT after treatment with rivastgmine further support the notion of an enhancement of cholinergic neurotransmission by AChE/ChE inhibitors. The observation of a greater expression of this cholinergic marker in SHR suggest that AChE inhibition may provide beneficial effects on cholinergic neurotransmission in an animal model of VaD.     

Effects of repeated administration of rolipram, a cAMP-specific phosphodiesterase inhibitor, on acetylcholinergic indices in the aged rat brain

The effects of repeated treatment of rolipram, a cAMP specific phosphodiesterase inhibitor (0.1 mg/kg/day i.p., 14 days), on several neuronal cholinergic indices, especially on those in aged rats were examined. In young-adult rats, rolipram treatment increased choline acetyltransferase (ChAT) activity (V(max)value) in the striatum as well as in thalamus + midbrain, whereas it decreased choline esterase activity in the hippocampus. The ChAT activity (V(max)value) and the M1-R binding (B(max)value) in the aged control rats were significantly reduced in all the brain regions examined, compared with the young-adult rats, but consecutive rolipram treatment ameliorated the reductions of both indices in the frontal cortex and the hippocampus to approximately the young-adult control levels. Since high membrane binding site concentrations for rolipram itself were revealed in the frontal cortex and the hippocampus, where the rolipram treatment showed ameliorating effects on the ChAT activity and the M1-R binding, the present findings indicate that repeated rolipram administration easily affects these two brain regions. Thus, repeated rolipram administration could restore both the presynaptic ChAT activity and the postsynaptic muscarinic cholinergic M1-R binding which are decreased with aging.     

丰富环境训练对低碘大鼠中枢胆碱能神经元的作用初探

对碘缺乏大鼠从生后２５天起给予丰富环境训练，然后在４０日龄时测定脑重量、蛋白质、脱氧核糖核酸（ＤＮＡ）、乙酰胆碱转移酶（ＣｈＡＴ）、乙酰胆碱酯酶（ＡＣｈＥ）各亚类。结果表明，丰富环境的后天训练对脑的基本构成、细胞数目无明显改善作用。但后天训练可促进大鼠海马、大脑皮层和小脑胆碱能神经元功能活动，尤其是突触部分得以一定程度地改善。     

Age-related learning and memory deficits in rats: role of altered brain neurotransmitters,acetylcholinesterase activity and changes in antioxidant defense system

Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino–Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.     

Changes in muscarinic receptors on lymphocytes in normal aging and Alzheimer's disease

It has been previously reported that responses of T-lymphocytes to stimulation by phytohemagglutinin declined as age advanced. However, it has not been demonstrated whether receptor binding capacity decreased with age. The potent muscarinic cholinergic antagonist, 3-quinuclidinyl benzilate (QNB) was used to detect the characterization of muscarinic acetylcholine receptors (mAChR) on human lymphocytes. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for the [3H]-QNB. Three age groups of healthy female adults were examined: 42-49 (N = 7), 50-59 (N = 7) and 60-69 years old (N = 8). Moreover, we studied mAChR on lymphocytes from 11 patients (54-65 years old, female) with probable Alzheimer's Disease. Specific binding is saturable, proportional to cell concentration, and can be displaced by atropine. For control subjects (age range 42-69 years old, N = 22), a positive correlation (r = 0.634, alpha less than 0.01) was found between Kd and age. Also positive correlation between Bmax and age was shown to be strong (r = 0.434, alpha less than 0.05), The regression equations are: Y = 3.25X - 109.5 (Kd); Y = 24.7X - 201.8 (Bmax); where, X and Y designate the age of individuals and Kd (or Bmax), respectively. Hence, for patients with Alzheimer's Diseases, the correlation between Kd and age, and between Bmax and age, were weak (r = -0.352, 0.011, not significant, respectively). No significant change in Kd or Bmax was obtained on lymphocytes from patients, compared to age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes of muscarinic cholinergic binding by human lymphocytes with normal aging and Alzheimer's disease]

A potent, new muscarinic cholinergic antagonist, L-[N-methyl-3H] quinuclidinyl benzilate methyl chloride ([3H-]-NM-QNB) was used to detect functional changes of muscarinic acetylcholine receptors (mAChR) on human lymphocytes in relation to age. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for [3H]-NM-QNB. We examined Group of healthy adult females (41-66 years old, N = 34) and patients with "probable" Alzheimer's disease (55-75 years old, N = 11). It was shown that mAChR on lymphocytes were divided into two subtypes; high affinity (Ms) and low affinity types (Mw) for a ligand, [3H]-NM-QNB. For the healthy controls (age range 41-66 years old, N = 31), a negative correlation (r = -0.172) was found between Kd (Ms) and age. Also the negative correlation between Bmax (Ms) and age was shown to be weak (r = -0.164). The regression equations are: Y = 11.9X + 1306.4 (Kd(Ms); N = 31) Y = -80.6X + 8296.1 (Bmax(Ms); N = 31) where, X and Y designate the age of individuals and Kd (or Bmax), respectively. Hence, for patients with Alzheimer's disease, no significant changes with age in Kd (Ms) or Bmax (Ms) were obtained. Furthermore, correlations between the stage of clinical dementia of patients and Kd (Ms), and between the staging and Bmax (Ms) were shown to be strong (p less than 0.05). Significant change (p less than 0.05) in Bmax (Ms) was recognized in lymphocytes from patients with Alzheimer's disease (N = 11), compared with age-matched controls (N = 20).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dementia without cholinergic deficit

We examined the role of cholinergic system in multi-infarct dementia (MID) by measuring acetylcholinesterase (AChE) activities in cerebrospinal fluid (CSF) of clinically diagnosed MID patients, Alzheimer's disease (AD) patients and controls. In spite of the similar clinical severity of dementia, MID patients had unaltered AChE levels, whereas AD patients had significantly reduced AChE levels in CSF when compared to controls. In the autopsy study we analyzed choline acetyltransferase (ChAT) levels in four cortical brain areas from clinically and neuropathologically studied AD patients, demented non-AD patients and controls. ChAT activities in the cerebral cortex in non-AD patients were on the same level as in controls, but AD patients had a marked loss of ChAT activity in all four cortical brain areas studied. Although cholinergic deficit is a usual phenomenon associated with cognitive failure, severe dementia can exist without cholinergic dysfunction.