G proteins (Gi,Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change

Summary We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated.     

Transplantation of central nervous tissue

Studies of post-lesional reorganization of central nervous connections have shown that central nerve fibers respond to nearby denervation by sprouting and formation of new terminals. The connections in the central nervous system (CNS) are accordingly much more plastic than was thought for a long time. This has revived the interest in transplantation of central nervous tissue. In this study we present some historical data on CNS transplantation supplemented by recent results obtained in our laboratory. Pieces of hippocampal tissue from embryonic or early postnatal rats were transplanted to different parts of the brain of littermates or adult rats. About two-thirds of the transplants were recovered after survival times ranging from 4 d to 2 years, and their cytological organization and intrinsic connections were monitored by cell and fiber stains and histochemical methods (AChE staining and Timm sulphide silver method). Comparison with both a normal and a lesioned control material revealed that in most transplants the tissue had developed as it does when left in situ in the donor brain, but deprived of its major afferent connections. In several instances we found evidence of a major exchange of connections between the transplants and host brains. The conditions needed for this to occur appeared to involve growth stimulation of host brain fibers by transection (host to transplant) and denervation of host neuropil (transplant to host). In cases where these conditions are met, the use of transplants may have future implications in attempts to repair lesions in the central nervous systems.     

Glioblastoma multiforme of the hippocampus in advanced Alzheimer''s disease

An 87-year-old woman suffered from Alzheimer's disease diagnosed 6 years prior to her death. Autopsy showed in addition to far-advanced Alzheimer's disease, a large, partially necrotic glioblastoma occupying her right hippocampus. Occurrence of a glial neoplasm in Alzheimer's disease could well be coincidental, since both entities are fairly common in elderly individuals; it is however, uncommon for gliomas to centre on the hippocampus itself. For these reasons it is possible (although cannot be proven from a single case), that florid reactive gliosis commonly associated with Alzheimer's disease, may have played a role in eventually initiating neoplastic proliferation of astrocytes in this patient.     

Effect of CNTF on low-affinity NGF receptor expression by cultured neurons from different rat brain regions.

Our previous work indicated that in E14 embryonic rat spinal cord cultures ciliary neuronotrophic factor (CNTF) exerted (1) a survival-promoting effect on motor neurons and on a large population of unidentified neurons, and (2) a regulatory role on the expression of ChAT and low affinity NGF receptor (LNGFR) in a population of small/medium-sized neurons. In the present study, we examined the effect of CNTF on the expression of LNGFR in cultures of different regions from the E18 embryonic rat brain, namely cortex, septum, striatum, mesencephalon, hippocampus, brainstem, and cerebellum. The number of LNGFR-positive neurons (stained with the 192-IgG monoclonal antibody) was determined in untreated cultures and in cultures treated for 6 days (0-6) with human recombinant CNTF. To distinguish between effects on survival and on LNGFR expression, experiments were performed in which CNTF was administered only for the last 48 h of the culture (from days 4-6). LNGFR positive neurons were found in the cultures of all the regions examined. In each one of them, CNTF increased the number of LNGFR-positive neurons by three- to fourfold after 6 days of treatment. In the striatum, septum, mesencephalon, and cerebellum, the effect of CNTF was shown to be on the regulation of LNGFR expression and not on survival. In cultures from the cortex, hippocampus and brainstem, a survival-promoting role of CNTF could be demonstrated. The effect of CNTF was dose dependent, with half-maximal effects (ED50) achieved at 2-4.5 TU/ml for all the brain regions. Maximal effects were reached at 100-250 TU/ml. From these results, we conclude that (1) there exists a wide spectrum of CNTF-responsive neurons in the central nervous system, and (2) CNTF plays an important and widespread role in regulating the expression of the LNGFR in neurons.     

Prenatal Stress Increases the Hypothalamo-Pituitary-Adrenal Axis Response in Young and Adult Rats

Prenatal stress is considered as an early epigenetic factor able to induce long-lasting alterations in brain structures and functions. It is still unclear whether prenatal stress can induce long-lasting modifications in the hypothalamo-pituitary-adrenal axis. To test this possibility the effects of restraint stress in pregnant rats during the third week of gestation were investigated in the functional properties of the hypothalamo-pituitary-adrenal axis and hippocampal type I and type II corticosteroid receptors in the male offspring at 3, 21 and 90 days of age. Plasma corticosterone was significantly elevated in prenatally-stressed rats at 3 and 21 days after exposure to novelty. At 90 days of age, prenatally-stressed rats showed a longer duration of corticosterone secretion after exposure to novelty. No change was observed for type I and type II receptor densities 3 days after birth, but both receptor subtypes were decreased in the hippocampus of prenatally-stressed offspring at 21 and 90 days of life. These findings suggest that prenatal stress produces long term changes in the hypothalamo-pituitary-adrenal axis in the offspring.     

电针对大鼠海马兴奋性突触后电位长时程增强的作用

目的 观察电针对麻醉状态下正常和东莨菪碱引起的学习记忆减退模型大鼠海马突触EPSP长时程增强(LTP)的作用。方法 引导大鼠海马齿状回颗粒细胞层突触后兴奋性电位群(EPSPs)，强直刺激(HFS)大脑皮层前穿质区引起海马突触LTP反应；用东莨菪碱制备学习记忆障碍模型；观察电针大椎和肾俞穴对正常和模型大鼠海马LTP的影响。结果 电针对HFS诱发的海马突触LTP效应，其作用强于未电针组，部分参数和时段有统计学意义(P＜0．05)，且维持时间长于后者；东莨菪碱i．p可显著抑制HFS诱发的海马突触LTP(P＜0．01)，电针能显著对抗这一抑制作用(P＜0．01；P＜0．05)。结论 电针对HFS引起的海马突触LTP有一定的易化作用，并对东莨菪碱引起的学习记忆障碍有显著的对抗作用。     

吗啡导致猕猴海马神经元自发放电节律转变

目的 分析吗啡对猕猴海马神经元自发放电节律的影响。方法 分析注射吗啡后猕猴海马神经元自发放电节律变化情况，并用数学方法加以验证。结果 在吗啡作用下海马神经元自发放电节律会发生转变，纳络酮可以逆转这种转变，共观察到种转变形式。为了研究这种转变的动力学机制，用数学模型模拟吗啡对神经元自发放电节律的影响，得到了与在体实验一致的结果。结论 在吗啡作用下海马神经自发放电节律发生转变。利用数学模型研究发现节律转变的原因是吗啡改变了膜上钠，钾，超极化电流等离子通道的功能所致，节律转变的过程存在着混沌规律。     

二硫化碳对大鼠海马一氧化氮合酶活力和基因表达的影响

目的:探讨二硫化碳(CS2)对大鼠海马一氧化氮合酶(NOS)活力和基因表达的影响。方法:以吸入染毒法制作不同浓度CS2中毒大鼠模型:染毒2个月后,用Morris水迷宫法检测实验大鼠的学习记忆功能;以NOS测定试剂盒测定大鼠海马NOS活力;以半定量逆转录一聚合酶链式反应(RT-PCR)法测定神经元型一氧化氮合酶(nNOS)mRNA 含量的变化。结果:Morris水迷宫测试显示染毒后大鼠平均逃逸潜伏期较对照组延长,差异有显著性;各CS2染毒组大鼠海马NOS活性降低,与对照组比较差异有显著性,随CS2浓度的增加NOS活性降低,各染毒组间比较差异有显著性差异;染毒后海马nNOS mRNA含量比对照组显著减少,与CS2浓度呈剂量依赖关系,差异有显著性意义。结论:CS2致大鼠海马NOS活力降低及nNOS mRNA含量减少可能是CS2干扰学习记忆功能的机制之一。     

实验性蛛网膜下腔出血后脑血管痉挛兔海马组织中Bcl-2和Bax mRNA的表达

目的：探讨蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)造成脑损伤的机制．方法：用反转录聚合酶链式反应(RT—PCB)技术检测兔SAH后CVS时海马组织Bcl—2和BaxmRNA的表达变化．结果：Bcl—2mBNA的表达水平在SAH组1d时即开始下降，3d时降至最低，持续至7d．SAH组海马组织中BaxmRNA的表达呈上升趋势，3d时达最高，7d时仍显著高于正常组．在假手术组海马组织内的Bcl—2和BaxmRNA的表达水平保持相对恒定．结论：Bcl—2和Bax可能参与了SAH后CVS所造成的海马神经元损伤过程。     

Evidence for NMDA receptor involvement in environmentally induced dentate gyrus plasticity.

Research has demonstrated environmentally induced plasticity of hippocampal dentate gyrus-evoked potentials. Other research has shown a role of the NMDA receptor in dentate gyrus long-term potentiation (LTP). The authors tested the role of the NMDA receptor in one form of environmentally induced plasticity, in which transferring animals from their home cages to another environment results in significant excitatory postsynaptic potential (EPSP) enhancement and concomitant depression of the population spike. Rats were chronically implanted with stimulating electrodes in the perforant path and recording electrodes in the dentate gyrus bilaterally. Evoked potentials were recorded from freely behaving rats for four 20-minute sessions (1/wk), which took place immediately following an environmental transfer. Rats received 0.00, 0.05, 0.08, or 0.10 mg/kg MK-801 s.c. 30 minutes prior to recording sessions in either an ascending- or descending-dose series. Results showed that MK-801 produced a reduction of the EPSP enhancement, which takes place over the 20-minute session. The effects of MK-801 on spike depression varied as a function of dose series and time within a session, suggesting a long-term effect of MK-801 on spike depression. There was no detected effect of MK-801 on behavior. Results suggest a role of the NMDA receptor in this form of environmentally induced plasticity with different effects of NMDA receptor antagonism on EPSP enhancement and spike depression.