Treatment Strategies Targeting Excess Hippocampal Activity Benefit Aged Rats with Cognitive Impairment

Excess neural activity in the CA3 region of the hippocampus has been linked to memory impairment in aged rats. We tested whether interventions aimed at reducing this excess activity would improve memory performance. Aged (24 to 28 months old) male Long–Evans rats were characterized in a spatial memory task known to depend on the functional integrity of the hippocampus, such that aged rats with identified memory impairment were used in a series of experiments. Overexpression of the inhibitory neuropeptide Y 13–36 in the CA3 via adeno-associated viral transduction was found to improve hippocampal-dependent long-term memory in aged rats, which had been characterized with impairment. Subsequent experiments with two commonly used antiepileptic agents, sodium valproate and levetiracetam, similarly produced dose-dependent memory improvement in such aged rats. Improved spatial memory with low doses of these agents was observed in both appetitve and aversive spatial tasks. The benefits of these different modalities of treatment are consistent with the concept that excess activity in the CA3 region of the hippocampus is a dysfunctional condition that may have a key role underlying age-related impairment in hippocampal-dependent memory processes. Because increased hippocampal activation occurs in age-related memory impairment in humans as observed in functional neuroimaging, the current findings also suggest that low doses of certain antiepileptic drugs in cognitively impaired elderly humans may have therapeutic potential and point to novel targets for this indication.     

Calretinin immunoreactivity in the brain of the zebrafish, Danio rerio: distribution and comparison with some neuropeptides and neurotransmitter-synthesizing enzymes. II. Midbrain, hindbrain, and rostral spinal cord

The distribution of calretinin (CR) in the brainstem and rostral spinal cord of the adult zebrafish was studied by using immunocytochemical techniques. For analysis of some brainstem nuclei and regions, CR distribution was compared with that of complementary markers (choline acetyltransferase, glutamic acid decarboxylase, tyrosine hydroxylase, neuropeptide Y). The results reveal that CR is a marker of various neuronal populations distributed throughout the brainstem, including numerous cells in the optic tectum, torus semicircularis, secondary gustatory nucleus, reticular formation, somatomotor column, gustatory lobes, octavolateral area, and inferior olive, as well as of characteristic tracts of fibers and neuropil. These results indicate that CR may prove useful for characterizing a number of neuronal subpopulations in zebrafish. Comparison of the distribution of CR observed in the brainstem of zebrafish with that reported in an advanced teleost (the gray mullet) revealed a number of similarities, and also some interesting differences. Our results indicate that many brainstem neuronal populations have maintained the CR phenotype in widely divergent teleost lines, so CR studies may prove very useful for comparative analysis.     

稳压灵对肝阳上亢型高血压病患者疗效及对NPY、CRP、HCY水平的影响

目的观察稳压灵对2级高血压病肝阳上亢型患者血压的影响、中医证候的疗效及对血浆神经肽Y（NPY）、血清C-反应蛋白（CRP）、同型半胱氨酸（HCY）水平的影响。方法 1.随机选取2级高血压肝阳上亢型患者60例,并按随机化原则分为治疗组和西药对照组各30例,分别给予稳压灵＋西药和单纯西药治疗;2.两组治疗前后均测定血压、血NPY、CRP、HCY,计算中医证候积分;结果 1.治疗后治疗组与对照组血浆NPY、CRP、HCY含量较治疗前均明显降低,差异非常显著（P〈0.01）,但治疗组比对照组有一定优势（P〈0.05）;2.两组治疗后症状均有改善,但治疗组较对照组有一定优势（P〈0.05）。结论与单纯西药治疗相比,稳压灵加西药治疗肝阳上亢型2级高血压病临床症状改善及血压控制效果更佳,同时对血浆NPY、CRP、HCY影响更大。     

Neurotransmitter segregation: functional and plastic implications

Synaptic cotransmission is the ability of neurons to use more than one transmitter to convey synaptic signals. Cotransmission was originally described as the presence of a classic transmitter, which conveys main signal, along one or more cotransmitters that modulate transmission, later on, it was found cotransmission of classic transmitters. It has been generally accepted that neurons store and release the same set of transmitters in all their synaptic processes. However, some findings that show axon endings of individual neurons storing and releasing different sets of transmitters, are not in accordance with this assumption, and give support to the hypothesis that neurons can segregate transmitters to different synapses. Here, we review the studies showing segregation of transmitters in invertebrate and mammalian central nervous system neurons, and correlate them with our results obtained in sympathetic neurons. Our data show that these neurons segregate even classic transmitters to separated axons. Based on our data we suggest that segregation is a plastic phenomenon and responds to functional synaptic requirements, and to 'environmental' cues such as neurotrophins. We propose that neurons have the machinery to guide the different molecules required in synaptic transmission through axons and sort them to different axon endings. We believe that transmitter segregation improves neuron interactions during cotransmission and gives them selective and better control of synaptic plasticity.     

Ghrelin and reproductive disorders

Ghrelin is an important factor involved in most of the metabolic and hormonal signals which adapt the reproductive functions in conditions of altered energy balance. Moreover, the coordinated role of leptin and ghrelin appears in fact to have a specific role in the regulation of puberty. Systemic action of ghrelin on the reproductive axis involves the control of the hypothalamic-pituitary-gondal axis. In addition, it has been shown that ghrelin may directly act at a gonadal level in both females and males. Available data also demonstrate that sex steroid hormones and gonadotropins may in turn regulate the gonadal effect of ghrelin, as documented by studies performed in females with the polycystic ovary syndrome and in hypogonadal men. Notably, recent studies also confirm a potentially important role for ghrelin in fetal and neonatal energy balance, and specifically in allowing fetal adaptation to an adverse intrauterine environment.     

Effect of peripheral 2-DG on opioid and neuropeptide Y gene expression

It is well known that 2-Deoxy-d-glucose (2-DG) blocks intracellular utilization of glucose and increases food intake. The aim of the present study was to determine whether administration of 2-DG alters gene expression of the orexigenic peptides, neuropeptide Y (NPY) and endogenous opioids, in the arcuate nucleus of the hypothalamus (ARC). Male Sprague–Dawley rats were injected peripherally (i.p.) with 2-DG (200 or 400 mg/kg body weight) and were sacrificed at 2 or 6 h post injection. Half of the animals were given ad libitum access to food whereas the other half of the animals were food-deprived. 2-DG increased food intake fourfold compared to saline injected animals, but did not affect NPY mRNA levels after 2 h. Messenger RNA levels of ProDynorphin (proDYN), but not pro-opiomelanocortin (POMC) nor proEnkephalin (proENK) were significantly decreased 2 h after 2-DG injection. Administration of 400 mg/kg of 2-DG increased mRNA levels of NPY in the arcuate nucleus after six h, but only in those animals not receiving food.     

人视皮质17区NPY样免疫反应阳性神经元的形态、分布和发育

采用免疫细胞化学技术ABC法，以引产死亡胎儿13例和死亡足月产新生儿4例为材料．对其树皮质Brodmann17区NPY样阳性结构进行了观察．发现新生儿视皮质NPY样阳性神经元主要位于灰-白质交界区和浅层白质内．NPY样阳性神经元为非锥体形神经元，以多极和双簇状神经元为主，还有部分双极和不成熟神经元．阳性神经元有大量的突起，在交界区和浅层白质内形成浓密的纤维网，而皮质层内种经纤维相当稀疏．发育学研究显示，胎龄22周已有阳性神经元出现，随着胎龄的增长，阳性神经元的密度、体积、突起的数量和长度不断增长，成熟神经元的比例也逐渐增加，阳性神经元逐渐向皮质迁移．     

Immunohistochemical analysis of the early ontogeny of the neuropeptide Y system in rat brain

The distribution of neuropeptide Y in the developing rat brain was studied with immunocytochemistry, using the peroxidase-antiperoxidase method. Immunoreactive perikarya were first seen on embryonic day 13 and staining of fibres appeared from embryonic day 15 onwards: perikaryal staining was generally more intense prenatally than after birth. Areas rich in neuropeptide Y immunostaining included the monoaminergic regions of the brain stem from embryonic day 13 (especially the lateral reticular nucleus and the medullary reticular formation), the dorsal mesencephalon (with spots of immunoreactivity in the outer subventricular zone at embryonic days 13 or 14 and many cells and fibres in the inferior colliculus from embryonic days 16-20) and the olfactory tubercle/ventral striatum from embryonic day 15 until birth. The period of development of cortical neurones extended from embryonic day 19 until postnatal day 21. A hitherto unreported feature unique to neuropeptide Y was the presence in certain parts of the cerebral cortex of transient cells at the base of the cortical plate bearing radial processes which transverse its width. They were present from embryonic day 17 until postnatal day 4 and were maximally developed at embryonic days 20 or 21, contributing at this age a substantial fibre projection through the immature corpus callosum. The abundance of neuropeptide Y in the prenatal rat brain suggests it may play an important role in development.