钙调节激素对培养的纹状体细胞Ca^2＋转运的影响

本文观察了钙调节激素——甲状旁腺素(PTH)和降钙素(CT)对培养成活的脑纹状体神经细胞~(45)Ca转运的影响。结果表明,PTH(10-~7M)明显促进静息状态和去极化状态下细胞对~(45)Ca的摄取,并抑制去极化状态下的~(45)Ca释放,使胞内~(45)Ca净摄取量明显增加。CT(1u/ml)对细胞在静息状态下的~(45)Ca摄取无影响,但抑制去极化细胞的~(45)Ca摄取与释放,使胞内~(45)Ca净摄取最明显减少。结果提示,这两种钙调节激素可能通过影响神经细胞内的Ca~(2+)水平,参与某些中枢性的生理功能的调节。     

缺血等因素对大鼠心肌线粒体Ca^2＋转运的影响

本研究检测了体外缺血等因素对心肌线粒体Ca~(2+)转运的影响。结果表明,缺血明显抑制线粒体Ca~(2+)-ATP酶活性及~(45)Ca摄取率。缺血10分钟时,线粒体Ca~(2+)-ATP酶活性开始下降,40分钟时显著降低,~(45)Ca摄取率的变化也呈类似趋势。去甲肾上腺素及cAMP对线粒体Ca~(2+)-ATP酶活性,~(45)Ca摄取率无任何影响。无机磷对线粒体Ca~(2+)-ATP酶有轻微的抑制作用,二磷酸腺苷对谚酶活性有明显抑制作用,其IC_(50)值为2.5mmol/L。     

中药鸡血藤的镇痛实验研究

采用小鼠热板法、小鼠醋酸扭体法和小鼠热水缩尾法观察25%、50%和100%三种浓度的鸡血藤水煎液的镇痛作用。结果发现三种浓度的鸡血藤水煎液均可使热板所致小鼠舔足的痛阈值明显提高(P<0.05),痛阈提高率最高达112.17%;可使醋酸所致小鼠扭体潜伏期明显延长(P<0.01),扭体次数明显减少(P<0.01),抑制率最高达64.74%;可使热水所致小鼠缩尾潜伏期明显延长(P<0.01),痛阈提高率最高达81.79%。从而证实鸡血藤水煎液具有镇痛作用。     

Wnt/β-catenin信号参与慢性痛引起的小鼠海马神经元发生减少

目的:研究小鼠慢性痛模型中海马神经元发生减弱的现象,并从Wnt/β-catenin信号的角度探索相关机制,以及过表达β-catenin对慢性痛小鼠学习记忆能力的影响。方法:采用选择性坐骨神经损伤(spared nerve injury,SNI)模型,利用Brd U/DCX免疫荧光双标研究神经元发生;采用Wnt信号报告基因Topgal小鼠研究Wnt信号的改变;利用条件性过表达β-catenin的Nestin-Cre ER:β-catenin EX3~(loxp/+)小鼠研究过度激活Wnt信号对慢性痛小鼠海马神经元发生及学习记忆的影响;利用Morris水迷宫评估小鼠的空间学习记忆能力。结果:SNI后小鼠的机械和热痛阈显著下降,持续至少3周。Brd U/DCX免疫荧光双标显示SNI小鼠海马神经元发生明显减弱。Wnt信号报告基因β-gal在海马神经干细胞的表达降低。在SNI小鼠的成年神经干细胞中过表达β-catenin可显著促进海马神经元发生,并增强小鼠的空间记忆能力。结论:Wnt/β-catenin信号参与介导慢性痛引起的海马神经元发生减弱,增强Wnt信号可改善SNI小鼠海马的神经元发生及其学习记忆能力。     

坐骨神经选择性损伤痛模型小鼠脊髓背角线粒体解偶连蛋白UCP4的表达变化

目的:观察线粒体保护蛋白解偶联蛋白4(uncoupling protein 4,UCP4)在坐骨神经选择性损伤(sparednerve injury,SNI)模型小鼠脊髓背角中的表达变化。方法:健康C57BL/6小鼠分为假手术对照组(n=21)和坐骨神经分支选择性损伤SNI组(n=21),实验组损伤后饲养3,7,14 d。行为学采用测定小鼠热痛阈和Von Frey机械性痛阈;用免疫荧光组织化学染色法检测对比小鼠脊髓L3-6节段背角内UCP4免疫阳性细胞的数量。结果:SNI术后3 d,小鼠手术侧热痛阈和机械性痛阈明显低于假手术组,术后14 d达最低值。UCP4分布于正常小鼠脊髓背角,SNI后3 d损伤组小鼠脊髓背角中的UCP4表达降低,图像分析表明UCP4的光密度与对照组比较,差异有统计学意义(P<0.05);脊髓背角中UCP4的表达在14 d时其降低程度最明显,图像分析表明光密度与对照组、3d和7 d比较,差异均有统计学意义(P<0.05)。结论:SNI后脊髓背角线粒体保护蛋白UCP4表达降低可能参与神经病理性疼痛的中枢敏化过程。     

氯化三乙基锡对大鼠C6脑胶质瘤细胞增殖和细胞周期的影响

目的探讨氯化三乙基锡(triethyltin chloride,TETC)对体外培养大鼠C6脑胶质瘤细胞增殖和细胞周期的影响。方法采用MTT法检测0.5、1.0和2.0μmol/L TETC对体外培养大鼠C6脑胶质瘤细胞作用24h和48h后细胞增殖的影响、采用细胞形态学观察及流式细胞术(FCM)方法检测0.5、1.0和2.0μmol/L TETC对体外培养大鼠C6脑胶质瘤细胞作用48h后细胞增殖和细胞周期的影响。结果MTT法及细胞形态学观察均检测到0.5、1.0和2.0μmol/L TETC在体外均可抑制C6细胞增殖,C6细胞增殖率存在着剂量依赖性和时间依赖性降低趋势;TETC可将C6细胞阻滞在G0/G1期。结论TETC可抑制体外培养大鼠C6胶质瘤细胞增殖,其机制可能与C6细胞周期阻滞在G0/G1期有关。     

锌对辣椒素致痛模型小鼠脊髓c-fos表达和动物行为学的影响

目的研究锌对辣椒素致痛模型小鼠脊髓c-fos表达和动物行为学的影响。方法 48只C57/BL6小鼠随机分为4组,采用足底注射辣椒素(0.5%,5μl)制备神经病理性疼痛(NPP)小鼠模型:对照组(Con)给予适锌饲料(锌30mg/kg/d)喂养2周后,右后足底注射溶剂(吐温80、酒精和生理盐水混合液);适锌喂养组(N-NPP)给予适锌饲料(锌30mg/kg/d)喂养2周后足底注射辣椒素;低锌喂养组(L-NPP)给予低锌饲料(锌0.85mg/kg/d)喂养2周后注射辣椒素;高锌喂养组(H-NPP)给予硫酸锌水溶液(227mg/L/d)喂养2周后注射辣椒素。应用原子吸收光谱技术、动物行为学观察、免疫组织化学和图像分析技术检测注射辣椒素后7d锌对脊髓cfos表达和动物行为学的影响。结果高锌喂养能显著增加血清和脊髓中锌的含量,使脊髓c-fos表达下调,机械痛阈增高,痛敏减弱(0.01);而低锌喂养加重血清和脊髓的缺锌状态,脊髓c-fos表达上调,机械痛阈降低,痛敏增强(0.01)。结论锌能抑制辣椒素致痛模型小鼠脊髓c-fos的表达,降低痛敏。     

右美托咪定上调海马脑源性神经营养因子-酪氨酸激酶受体B的表达及改善完全费氏佐剂所致小鼠焦虑样和抑郁样行为

目的 探讨α2-肾上腺素受体激动剂右美托咪定(DEX)对完全弗氏佐剂(CFA)诱导疼痛模型小鼠焦虑样和抑郁样行为的影响及其可能的机制。方法 36只ICR雌鼠随机分成生理盐水(NS)组、CFA组和DEX+CFA组，每组n=12。向小鼠右后肢足底皮下注射10μl CFA建立慢性炎性疼痛模型，DEX+CFA组小鼠在痛阈检测前30 min腹腔注射0.025 mg/kg DEX,1次/1 d,持续7 d。实验采用von-frey纤维丝评价3组小鼠机械性痛阈值；采用旷场实验检测小鼠焦虑样行为；采用糖水偏好、悬尾实验和强迫游泳检测3组小鼠抑郁样行为；采用Western blotting检测3组小鼠海马肾上腺素能受体β₂(ADRB2)、脑源性神经营养因子(BDNF)、酪氨酸激酶B受体(TrkB)及突触相关蛋白谷氨酸受体1(GluR1)和GluR2的表达，每组n=8;采用免疫组织化学染色方法检测各组小鼠海马新生神经元标记物双肾上腺皮质激素(DCX)的表达情况，每组n=4。结果 痛阈检测结果显示，与NS组相比，CFA注射后的第1天、3天、7天小鼠机械痛阈值均显著降低(P<0.0...     

多巴胺受体阻滞剂协调吗啡镇痛及其镇痛机制分析

目的:观察低剂量多巴胺受体阻滞剂氟哌啶醇与阈下镇痛剂量吗啡合用对抗热刺激和醋酸致小鼠痛反应的作用,并初步分析其协同镇痛作用的主导机制。方法:采用热板法测试给予氟哌啶醇(0.3125mg/kg,0.625mg/kg,1.25mg/kg)、吗啡(3.125mg/kg,6.25mg/kg,12.5mg/kg)和氟哌啶醇(0.3125mg/kg)与吗啡(3.125mg/kg)合用,对热刺激致小鼠痛反应的变化及苯丙胺(10mg/kg)和纳洛酮(5.0mg/kg)对其合用小鼠痛反应的影响。采用扭体法测试给予氟哌啶醇(0.625mg/kg,1.25mg/kg,2.5mg/kg)、吗啡(1.25mg/kg,2.5mg/kg,5.0mg/kg)及氟哌啶醇(0.625mg/kg)与吗啡(1.25mg/kg)合用,对醋酸(0.7%,0.1mL/10g,ip)诱致小鼠扭体出现潜伏期、20min内扭体反应次数的影响。结果:氟哌啶醇与吗啡合用明显提高小鼠对热刺激致痛的痛阈,显著延长醋酸致小鼠扭体反应潜伏期和抑制扭体反应次数;纳洛酮可取消两者合用的协同镇痛效应,而苯丙胺无明显影响。结论:多巴胺受体阻滞剂氟哌啶醇与吗啡合用可产生协同镇痛作用,而吗啡在协同镇痛中起主导作用。     

PTH、Ca、P在肿瘤骨转移判断中的变化分析

目的 观察肿瘤患者血清甲状旁腺素(PTH)、钙(Ca)、磷(P)水平,探讨肿瘤患者PTH分泌情况及其对钙磷代谢的调节作用.方法 选择2018年1月至2021年4月在我院明确诊断为肿瘤的111例患者为研究对象,其中骨转移者36例,对其血清PTH、Ca、P水平进行回顾性分析.另外纳入48例健康体检者作为对照组.比较各组患者血清PTH、Ca、P水平.结果 血清PTH水平在骨转移组、非骨转移组、对照组间有差异(P=0.044),其中骨转移组血清PTH高于对照组和非骨转移组.血清总Ca、校正Ca、P水平在三组间有差异(P<0.001,P<0.001,P=0.001),其中非骨转移组患者血清总Ca、校正Ca低于对照组,非骨转移组患者血清P水平较对照组升高(P=0.003).血清校正Ca、P水平在PTH升高组、PTH正常组、PTH降低组间差异有统计学意义(P=0.024,P=0.049).血清校正Ca在PTH正常组高于降低组(P=0.019),血清P在PTH正常组低于降低组(P=0.049).结论 肿瘤患者血清PTH水平升高,对于肿瘤骨转移的判断有一定的临床参考意义.部分肿瘤患者分泌过多的PTH,但不一定影响血钙水平,应综合分析PTH升高而血钙正常的情况.     

Gangliosides and synaptosomal calcium homeostasis

In this study, depolarization-dependent (net) calcium transport and binding capacity to rat brain synaptosomes was investigated under conditions affecting the ganglioside composition of the synaptoplasmatic membranes. Specific interaction of the monosialoganglioside GM1 with the membrane, as observed in low (40 nM) concentration of ganglioside, resulted in significant inhibition of the maximal depolarization-induced calcium uptake. The changes in ganglioside composition of synaptosomes produced by N-ase treatment did not affect the maximal net Ca++ uptake. However both procedures resulted in the decrease of calculated half-time of the depolarization-induced calcium influx. Exposure of synaptosomes either to GM1 in 40 nM concentration or to N-ase led to a significant drop in 45Ca++ binding to the membrane and increase in the CTC-Ca++ fluorescence. The results suggest that gangliosides are potent modulators of synaptosomal calcium fluxes and equilibration in the membrane.     

Nitric oxide-mediated Ca++-influx in neuronal nuclei and cortical synaptosomes of normoxic and hypoxic newborn piglets.

Previous studies have shown that hypoxia results in the generation of nitric oxide (NO) free radicals in the cerebral cortex of newborn animals. The present study tested the hypothesis that NO increases Ca++-influx in neuronal nuclei as well as N-methyl-D aspartate (NMDA) receptor-mediated Ca++-influx in cortical synaptosomes of newborn piglets. Studies were performed in five normoxic (Nx) and 6 hypoxic (Hx) newborn piglets. Cerebral tissue hypoxia was documented by determining the levels of ATP and phosphocreatine (PCr). 45Ca++ -influx was determined in the presence of sodium nitroprusside (SNP, 10 microM), a NO donor, and peroxynitrite (10 microM). In the Hx group, ATP levels decreased to 1.40+or-0.69 vs 4.27+or-0.80 micromoles/g brain in the Nx group (P<0.05). Similarly, PCr levels decreased to 0.91+or-0.57 vs 3.40+or-0.99 micromoles/g brain (P<0.001). Nuclear 45Ca++-influx increased from 3.57+or-1.46 pmoles/mg protein in Nx nuclei to 8.64+or-3.50 in Hx nuclei (P<0.05). SNP increased neuronal nuclear Ca++ influx in the Nx from 3.57+or-1.46 to 5.47+or-2.52 pmoles/mg protein (P<0.05) but did not affect Ca++ influx in the Hx group (8.64+or-3.50 vs. 10.17+or-4.00 pmoles/mg protein). The level of Ca++ influx in the presence of SNP in Nx nuclei was similar to that seen in Hx nuclei alone. Peroxynitrite did not affect nuclear Ca++-influx in either Nx or Hx group. Synaptosomal Ca++-influx in the presence of glu + gly was 40+or-11 pmoles/mg protein in the Nx group and 80+or-16 pmoles/mg protein in the Hx group (P<0.05). Both SNP and peroxynitrite increased Ca++ influx in Nx and Hx synaptosomes. These results show that hypoxia results in increased nuclear and synaptosomal Ca++-influx. Further, the data demonstrate that NO increases intranuclear as well as intrasynaptosomal Ca++-influx and suggest that during hypoxia, the increase in intranuclear and intraynaptosomal Ca++ is NO-mediated. We propose that NO-mediated modification (by nitrosylation/nitration) of nuclear membrane high affinity Ca++-ATPase and neuronal membrane NMDA receptor, resulting in increased intranuclear and intracellular Ca++ influx, are potential NO-mediated mechanisms of Hx neuronal injury.     

Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.

1. 45-Ca uptake by pinched-off nerve terminals (synaptosomes) of rat brain incubated in standard physiological saline (including 132 mM-Na + 5mM-K + 1-2 mM-Ca) at 30 degrees C averages about 0-5 mumole Ca per g protein per minute. This may be equivalent to a Ca influx of about 0-03 p-mole/cm-2 sec. 2. The rate of 45-Ca uptake is increased when the concentration of K in the medium is increased above 15-20 mM, K replacing Na isosmotically. Maximum stimulation, a three- to six-fold increase in the rate of Ca uptake, occurs when [K]o is about 60 mM. The effect of increased [K]o is reversible. 3. The K-stimulated Ca uptake is associated primarily with the nerve terminal fraction of brain homogenates. The entering Ca is not accompanied by extracellular markers such as mannitol or inulin. Replacement of external chloride by methylsulphate or sulphate does not prevent the stimulation by K. 4. The effects of external K are quantitatively mimicked by Rb. Caesium also stimulates Ca uptake, but is only about one fifth as effective as K or Rb; Li is ineffective. 5. Two other depolarizing agents also stimulate Ca uptake by synaptosomes: veratridine (7-5 times 10- minus 6 to 7-5 times 10- minus 5 M) and scorpion (Leirus quinquestriatus) venom (6-7 times 10- minus 7 to 6-7 times 10- minus g/ml.). The stimulatory effects of veratridine and scorpion venom, but not of increased [K] are blocked by 2 times 10- minus 7 M tetrodotoxin. 6. Internal K also influences the rate of 45-Ca uptake by synaptosomes: lowering [K]i reduces the stimulatory effect of external K and veratridine. 7. Replacement of external Na by choline markedly inhibits the response to veratridine, but has a much smaller effect on the response to increased [K]o. 8. The Ca uptake mechanism has an apparent dissociation constant for Ca (KCa) of about 0-8 mM. Increasing [K]o increases the maximal rate of Ca uptake, but has no effect on KCa. The K-induced 45-Ca uptake is competitively inhibited by Mg-2+, Mn-2+ and La-3+. 9. The release of acetylcholine and noradrenaline was also studied. Increasing [K]o stimulates external Ca-dependent acetylcholine release. Scorpion venom stimulates noradrenaline release from synaptosomes; this effect could be prevented by adding tetrodotoxin or removing external Ca. 10. These results indicate that synaptosomes may increase their permeability to Ca, accumulate Ca and release neural transmitter substances, when stimulated by depolarizing agents under appropriate physiological conditions.     

Kainate and quisqualate effects on rat presynaptic cortical receptors are metabotropic and non-additive.

The effects of quisqualate and kainate on synaptosomal inositol phosphate (InsP) labelling, 45Ca influx and intrasynaptosomal free calcium ([Ca2+]i) were investigated. Each agonist caused a concentration-dependent increase in both [Ca2+]i and InsP labelling: quisqualate, however, produced significantly larger responses in both parameters and at lower EC50 values. Neither quisqualate or kainate significantly affected 45Ca influx into synaptosomes, indicating that the observed increases in [Ca2+]i were due to mobilisation from intracellular stores. The concentration-dependent increases in [Ca2+]i promoted by quisqualate and kainate were monophasic, whereas the increases in InsP formation fitted well to a biphasic curve. The EC50 values suggest that both kainate and quisqualate initially mobilise calcium from inositol 1,4,5-trisphosphate (Ins 1,4,5-P3)-sensitive stores and that the resultant increases in [Ca2+]i will, above a certain threshold, promote further increases in InsP production by stimulation of Ca(2+)-dependent phospholipase C. When saturating concentrations of kainate and quisqualate were used in combination, the effects on both InsP labelling and [Ca2+]i were not additive but were slightly higher than those produced by kainate alone: combined administration of the two agonists had no effect on 45Ca influx. These results suggest that kainate acts as a partial agonist at the presynaptic quisqualate metabotropic glutamatergic receptor.     

Effect of acute hepatic encephalopathy on [3H]dopamine release from rat cerebral cortex and striatum in vitro: role of Ca2+

Hepatic encephalopathy (HE) is characterized by motor symptoms associated with disturbed functions of the dopaminergic systems, but the underlying mechanisms are not clear. A previous study from our laboratories revealed that HE, induced in rats by repeated treatment with thioacetamide, enhanced the 50 mM potassium (KCl)-stimulated release of newly loaded [3H]dopamine in both striatal and frontal cerebral cortical slices in the presence of Ca2+. In the present study we compared the effects of HE on dopamine release in striatal and frontal cerebral cortical slices and synaptosomes in the presence and absence of Ca2+. HE enhanced the KCl-stimulated [3H]dopamine release from striatal and frontal cortical synaptosomes in the presence of Ca2+ to the same extent as in slices prepared from the respective brain regions. In the absence of Ca2+ a slight reduction in dopamine release was observed in frontal cortical synaptosomes from HE rats when compared to control rats, while no effect of HE on the release was discernible in frontal cortical and striatal slices and striatal synaptosomes. We conclude that in both brain regions studied HE stimulates dopamine exocytosis triggered by Ca2+ influx without affecting the release mediated by means of plasma membrane transporters or exocytosis involving intraterminal Ca2+.     

Age-related changes in the subtypes of voltage-dependent calcium channels in rat brain cortical synapses

Age-related changes in the relative contribution of voltage-dependent calcium channel (VDCC) subtypes to depolarization-induced Ca(2+) influx and in the density of VDCC subtypes in cortical synapses were investigated using synaptosomes and their membrane preparations from brain cortices of Wistar rats. The relative contribution of VDCC subtypes to Ca(2+) influx was determined by measuring the inhibition of depolarization-induced Ca(2+) influx with four VDCC subtype-specific peptide blockers. In adult rat synaptosomes, L-, N-, P- and Q-type channels accounted for 24, 32, 27 and 12% of the total Ca(2+) influx, respectively. Brain aging significantly reduced the relative contributions of N- and P-type channels and increased the contribution of the channels resistant to the four blockers used. The densities of VDCC subtypes, determined by binding experiments using radiolabeled PN200 -110, omega-conotoxin GVIA and omega-conotoxin MVIIC, were found to be significantly decreased in aged synaptic plasma membranes. On the contrary, the dissociation constants of the blockers were not changed except for PN200-110-sensitive L-type channels. These results suggest that aging alters the relative contributions of each VDCC subtype to depolarization-induced Ca(2+) influx and decreases the number of VDCCs in rat brain cortical synapses. These changes in VDCCs may lead to age-related hypofunction of synaptic neurotransmission in brain cortices.     

Alpha-latrotoxin and glycerotoxin differ in target specificity and in the mechanism of their neurotransmitter releasing action

alpha-Latrotoxin, a high molecular weight protein (130,000) purified from the venom of the black widow spider, and a partially purified neurotoxin, glycerotoxin, prepared from extracts of the jaw glands of the polichaete annelid Glycera convoluta, were previously found to induce similar effects (stimulation of quantal acetylcholine release) at the frog neuromuscular junction. In the present study parallel experiments performed with these two toxins revealed that only glycerotoxin was able to release acetylcholine from Torpedo electric organ synaptosomes, while alpha-latrotoxin did not affect release in this system. In contrast, alpha-latrotoxin stimulated release of dopamine from PC12 cells (a cloned neurosecretory cell line), whereas glycerotoxin was almost inactive. In rat brain synaptosomes both toxins were active. Preincubation of synaptosomal membranes with glycerotoxin was without effect on the subsequent binding of alpha-latrotoxin. Glycerotoxin application induced depolarization of synaptosomal plasma membrane, massive Ca2+ influx, marked increase of the cytosolic Ca2+ concentration, and stimulation of catecholamine release. The latter effect occurred to the same extent when glycerotoxin was applied either in complete medium (containing both Ca2+ and Mg2+), Ca2+-free medium or divalent cation-free medium. Some of these effects of glycerotoxin in rat brain synaptosomes (depolarization, increased Ca2+ influx and increased cytosolic Ca2+ concentration) resemble effects previously reported for alpha-latrotoxin. However, the secretory response induced by the latter was reduced in Ca2+-free, and abolished in divalent cation-free media. The different target specificity and the lack of binding competition of the two toxins could be due to their ability to recognize different receptors whose distribution overlap only in part in the cellular systems we have studied. The differences in action, on the other hand, could depend on postreceptor events, possibly related to the transmembrane insertion of toxin molecules demonstrated by others in artificial lipid membranes.     

Interleukin-1β Inhibits Glutamate Release in Hippocampus of Young,But Not Aged,Rats

The proinflammatory cytokine, interleukin-1, is synthesized in neuronal and glial cells and is released in response to stress/injury. IL-1 exerts profound effects on the central nervous system, which include an inhibitory effect on synaptic activity in hippocampus, a brain area expressing a high density of IL-1 receptors. We report that IL-1β has an inhibitory effect on KCl-stimulated release of glutamate and KCl-stimulated [⁴⁵Ca] influx in synaptosomes prepared from hippocampus of 4-month-old rats. These effects were inhibited by the endogenous receptor antagonist, IL-1ra, and by the phospholipase A₂ (PLA₂) inhibitor, quinacrine, suggesting that IL-1 receptor activation is coupled to PLA₂. An inhibitory effect of IL-1β on protein kinase C activity was also observed. KCl-induced calcium-dependent release and calcium influx, and protein kinase C activity were significantly decreased in hippocampal synaptosomes prepared from 22-month-old compared to 4-month-old animals. In contrast to the inhibitory effect of IL-1β in synaptosomes prepared from young adult animals, no effect was observed on release, calcium influx, or protein kinase C activity in synaptosomes prepared from aged animals. We report that there is an age-related increase in expression of IL-1β in hippocampus and propose that this change may underlie the attenuated responses to IL-1β in hippocampus of aged animals.     

Regulation of calcium levels in brain tissue from adult and aged rats.

The possibility that regulation of Ca2+ levels in brain nerve terminals is altered as the brain ages was examined in synaptosomes from adult and aged Fischer 344 rats. Free intrasynaptosomal [Ca2+]i was monitored with fura-2 as synaptosomes were depolarized with KCl, veratridine and ibotenic acid. With all three depolarizing agents, synaptosomes from aged animals reached higher free Ca2+ levels, and the maximal Ca2+ increases (delta Ca2+) estimated from computer assisted-fitting of the curves, ranged from 35% to 80% greater in synaptosomes from aged animals. The total Ca2+ content of the brain and of synaptosomes was also found to be considerably higher in aged than in adult animals. These results suggest that the aging process in brain is accompanied by alterations in both dynamic aspects of Ca2+ handling in nerve endings and the overall content of Ca2+ in the brain and synaptic terminals.