Long-term effects of nerve growth factor and neural transplants on behavior of rats with medial septal lesions

The present experiment investigated the interaction between exogenous nerve growth factor (NGF) and intrahippocampal septal grafts on the behavior of rats after a medial septum lesion. Young female rats received a bilateral injection of a fetal septal cell suspension into the dorsal hippocampus either immediately (immediate grafts) or 8 days after the lesion (delayed grafts). For delayed grafts, a higher concentration of endogenous neurotrophic factors can be assumed to be present in the deafferentated host tissue at the time of transplantation. One group of rats with lesions received NGF with the immediate grafts, another group received NGF alone. A sham-operated group and 3 groups with lesions (and given either immediate or delayed intrahippocampal saline injections, or no other treatment) constituted controls. The animals were tested for spontaneous alternation and for performance in a radial 8-arm maze, 1, 5 and 9 months postoperatively. Medial septal lesions reduced spontaneous alternation but, 9 months after surgery, recovery was observed in both lesion-control rats and in rats with delayed grafts (but not with immediate grafts). In the radial maze task, lesions produced a persistent impairment, although both immediate and delayed grafts reduced this deficit several months after surgery (more markedly and rapidly in the case of delayed grafts). NGF, however, increased the maze learning deficit especially 5 months postoperatively. These latter results are in contrast to findings of earlier studies showing transient beneficial effects of NGF administration. It is suggested that the effects of NGF in the present study might be due to an enhanced sprouting of sympathetic fibers into the hippocampal formation.     

帕金森病患者血清EGF和BDNF水平变化与认知障碍的关系

目的探讨帕金森病(PD)患者血清表皮生长因子(EGF)和脑源性神经营养因子(BDNF)的变化及其与认知功能的关系。方法入选PD患者76例和年龄、性别相匹配的40例健康对照组,记录PD患者的性别、年龄、病程、受教育年限、HoehnYahr(H-Y)分级,采用蒙特利尔认知评估量表(Mo CA)对所有研究对象认知功能进行评估,采用酶联免疫吸附法(ELISA)检测血清EGF和BDNF水平,并对结果进行分析。结果 PD组血清EGF、BDNF水平明显低于健康对照组[(745±148)ng·L~(-1)比(952±157)ng·L~(-1),P0.05;(5.1±3.1)μg·L~(-1)比(6.8±3.9)μg·L~(-1),P0.05];早期PD组与中晚期PD组血清EGF和BDNF水平无差异(P0.05);但合并轻度认知功能障碍(MCI)的PD组血清EGF水平低于无MCI的PD组[(713±146)ng·L~(-1)比(865±189)ng·L~(-1),P0.01];PD患者Mo CA评分与受教育年限(β=0.611,P0.01)、血清EGF水平(β=0.513,P0.01)呈正相关,与病程(β=-0.373,P0.05)、H-Y分级(β=-0.264,P0.05)呈负相关。结论 EGF和BDNF水平的改变可能参与了PD患者的发病机制;血清EGF水平的下降可能与PD患者的MCI具有相关性,其可能为PD患者合并认知功能障碍的潜在早期预测指标。     

Nicotinic, muscarinic and dopaminergic actions in the ventral hippocampus and the nucleus accumbens: effects on spatial working memory in rats

Acetylcholine (ACh) systems have been widely shown to be important for memory. In particular, ACh hippocampal neurons are critical for memory formation, though ACh innervation of other areas such as the nucleus accumbens may also be important. There has also been increasing interest in ACh and dopaminergic (DA) interactions with regard to short-term spatial memory. In a series of studies, we have found that ACh and DA agonists and antagonists given systemically interact to influence memory. The critical neural loci of these interactions are not currently known. In the present study, we used local infusion techniques to examine the role of ACh and DA transmitter systems in the nucleus accumbens and the ventral hippocampus on radial-arm maze (RAM) working memory performance. Into the nucleus accumbens of rats, we infused the nicotinic ACh agonist nicotine, the nicotinic ACh antagonist mecamylamine, the DA agonist apomorphine, or the DA antagonist haloperidol. Into the ventral hippocampus, we infused nicotine, mecamylamine, the muscarinic ACh agonist pilocarpine, or the muscarinic ACh antagonist, scopolamine. The nicotinic ACh and DA interaction was tested by a hippocampal infusion of mecamylamine alone or together with the DA D₂ agonist quinpirole given via subcutaneous injection. The results confirmed that both nicotinic and muscarinic ACh receptors in the ventral hippocampus play a significant role in spatial working memory. Blockade of either nicotinic or muscarinic ACh receptors caused significant impairments in RAM choice accuracy. However, infusion of either nicotinic or muscarinic agonists failed to improve choice accuracy. The interaction of DA D₂ systems is different with hippocampal nicotinic blockade than with general nicotinic blockade. Systemic administration of quinpirole potentiated the amnestic effect of mecamylamine infused into the ventral hippocampus, whereas it was previously found to reverse the amnestic effect of systemically administered mecamylamine. In contrast to the significant effects of mecamylamine in the hippocampus, no effects were found after infusion into the nucleus accumbens. Nicotine also was not found to have a significant effect on memory after intra-accumbens infusion. Neither the DA agonist apomorphine nor the DA antagonist haloperidol had a significant effect on memory after infusion into the nucleus accumbens. This study provides support for the involvement of nicotinic and muscarinic receptors in the ventral hippocampus in memory function. Ventral hippocampal nicotinic systems have significant interactions with D₂ systems, but these differ from their systemic interactions. In contrast, nicotinic ACh and DA systems in the nucleus accumbens were not found in the current study to be important for working memory performance in the RAM.     

The impact of environmental enrichment in laboratory rats--behavioural and neurochemical aspects

The provision of environmental enrichment (EE) for laboratory rats is recommended in European guidelines governing laboratory animal welfare. It is believed the EE implementation can improve animals’ well-being and EE has been used to demonstrate learning and plasticity of the brain in response to the environment. This review suggests that the definition and duration of EE varies considerably across laboratories. Notwithstanding this, some EE protocols have revealed profound effects on brain neurochemistry and resulting behaviour, suggesting that EE can have the potential to significantly modify these parameters in rats. For this review, a literature search was conducted using PubMed and the search terms “Environmental Enrichment” and “rats”. From the results of this search the most important variables for consideration in the implementation of EE are identified and summarised, and include cage size and housing density; rat age, sex and strain; duration of EE; the EE protocol and enrichment items employed; and the use of appropriate controls. The effects of EE in a number of behavioural tests and its effects on neurotransmitters, neurotrophic factors, stress hormones and neurogenesis and proliferation are outlined. The findings summarised in the present review show the range of EE protocols employed and their effects in tests of activity, learning and affect, as well neurochemical effects which mediate enhanced plasticity in the brain. EE, as is provided in many laboratories, may be of benefit to the animals, however it is important that future work aims to provide a better understanding of EE effects on research outcomes.