Hypoxia facilitates the survival of nucleus pulposus cells in serum deprivation by down-regulating excessive autophagy through restricting ROS generation

Nucleus pulposus (NP) cells reside in a hypoxic environment in vivo, while the mechanisms of how NP cells maintain survival under hypoxia are not clear. Autophagy is an important physiological response to hypoxia and implicated in the survival regulation in most types of cells. This study was designed to investigate the role of autophagy in the survival of NP cells under hypoxia. We found that appropriate autophagy activity was beneficial to the survival of NP cells in serum deprivation, while excessive autophagy led to death of the NP cells. Hypoxia facilitated the survival of NP cells in serum deprivation by down-regulating excessive autophagy. Hypoxia down-regulated the autophagy activity of NP cells through restricting the production of reactive oxygen species (ROS) and inactivating the AMPK/mTOR signaling pathway, and possibly through a pathway involving HIF-1α. We believed that understanding the autophagy response of NP cells to hypoxia and its role in cell survival had important clinical significance in the prevention and treatment of degenerative discogenic diseases.     

A Search for Discrete Cholinergic Nuclei in the Human Ventral Forebrain

Abstract: Slices cut from five frozen human brains were dissected into 2-mm cubes and assayed for choline acetyltransferase (ChAT) activity and protein content. A pattern of enrichment of ChAT activity was found ventral to the anterior commissure; this finding is consistent with the location of the enzyme in the cells of the nucleus basalis of Meynert. The region beneath the anterior commissure was the only place a discrete enrichment of activity could be found, and the precise topography of the enrichment was somewhat variable from brain to brain. The results are discussed in the light of recent knowledge concerning the source of the cortical cholinergic innervation.     

Effect of Quinolinic Acid in the Nucleus Basalis Magnocellularis on Cortical High-Affinity Choline Uptake

A transient 45% increase in cortical high-affinity choline uptake (HACU) was observed after an injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM) of the rat. This was followed by a steady decline in choline uptake, which resulted in a 46% decrease by day 7. Specific [3H]hemicholinium-3 binding to coronal brain sections showed a similar pattern following injections of QUIN into the nbM. The increase in cortical HACU elicited by QUIN appeared to be dose dependent.     

电刺激大鼠尾核头部对丘脑腹后外侧核痛相关神经元电活动的影响

丘脑腹后外侧核的神经元对伤害性刺激的反应形式主要为以下三种类型:痛兴奋神经元、痛抑制神经元和痛无关神经元。痛相关神经元的放电活动可被吗啡类药物所抑制。电刺激尾核头部对痛相关神经元主要产生抑制作用,尾核头部背侧的作用强于腹侧,且受不同刺激参数的影响。本文就以上结果在镇痛中的意义进行了讨论。     

核微管组织中心的研究

本文利用间接免疫荧光手段对间期核微管组织中心的性质进行了初步探讨。当分离核与6S微管蛋白保温后,用抗管蛋白抗体进行间接免疫荧光染色,在群体中只有极少数核上有微管生长。Triton X-100或溶血卵磷脂去膜核的实验证实能长微管的核是核膜缺失或破损核。用秋水仙素解聚核上长出的微管,可见核内荧光亮点数多于染色体数,说明核内微管组织中心数目多于着丝粒数,很可能包括着丝粒和一部分染色质颗粒。将秋水仙素和6S微管蛋白混合后与去膜核保温,结果6S微管蛋白与核内微管组织中心有亲和力。本文就这些结果进行了讨论。     

Interactions between central glutamatergic,catecholaminergic and cholinergic systems with regard to locomotor activity in monoamine-depleted mice

Summary Following injection of 5µg of the competitive NMDA receptor antagonist AP-5 into the nucleus accumbens, but not following injection of the same dose into the dorsal striatum, a pronounced locomotor stimulation in monoamine-depleted mice was produced; the-adrenoceptor agonist clonidine (1 mg/kg) administered ip caused a marked potentiation of an intraaccumbens AP-5 (2.5µg) injection.On the other hand, 10µg of AP-5 combined with an ip injection of clonidine (1 mg/kg) caused a marked locomotor stimulation following local application into the dorsal striatum but not following application into the prefrontal cortex. Likewise, in combination with systemically administered clonidine, a substantial locomotor stimulation was observed after application of the muscarine receptor antagonist methscopolamine (62µg) into the dorsal striatum but not into the prefrontal cortex.This study suggests that NMDA receptors in the nucleus accumbens exert an inhibitory influence on locomotor activity. The dorsal striatum may also be involved in such control via NMDA and muscarinic receptors.     

Anatomy,neurophysiology and functional aspects of the nucleus isthmi in salamanders of the family Plethodontidae

Summary Tongue-projecting plethodontid salamanders have massive direct ipsilateral retinal afferents to the tectum opticum as well as a large and well developed nucleus isthmi. Retrograde staining revealed two subnuclei: A ventral one projecting to the contralateral tectal hemisphere and a dorsal one projecting back to the ipsilateral side. The isthmic nuclei show a retinotopic organization, which is in register with that of the tectum. Electrophysiological recordings from nucleus-isthmi neurons revealed response properties that are very similar to those found in tectal neurons. Thus, there is no substantial processing of tectal neural activity in the nucleus isthmi. Measurements of peak latencies after electrical and light stimulation suggest the continuous coexistence of 4 representations of the visual field in the tectum mediated by (1) the contralateral and (2) the ipsilateral direct retinal afferents, (3) the uncrossed and (4) the crossed isthmo-tectal projection. (1) and (2) originate at the same moment in the retina and arrive simultaneously in the tectum. It is assumed that in plethodontid salamanders with massive ipsilateral retino-tectal projections depth perception based on disparity cues is achieved by comparison of these images.Representations mediated by (3) and (4) arriving in the tectum at the same time as (1) and (2) originate 10–30 ms earlier in the retina. It is hypothesized that these time differences between (1)/(2) and (3)/(4) are used to calculate three-dimensional trajectories of fast-moving prey objects.Abbreviations EL edge length - FDA fluoresceine dextranamine - RDA tetramethylrhodamine dextranamine - RF receptive field     

Nucleolar necklace formation in response to hemolymph ecdysteroid peaks.

Previous work on the last (fifth) larval stadium of Calpodes showed two phases of elaboration of epidermal nucleoli correlated with RNA synthesis, the first after ecdysis at the beginning of the intermolt and the second near the end of the stadium prior to molting. Both phases followed periods of elevated hemolymph ecdysteroid. The demonstration of four hemolymph ecdysteroid peaks and an improvement in the bismuth-staining procedure for nucleoli has prompted further study of nucleolar changes in relation to hemolymph edcysteroids. We have found that three of the four ecdysteroid peaks (I, II and IV) are followed by nucleolar changes. The exception is the commitment peak (III) for which there is no corresponding nucleolar change. The three nucleolar cycles are similar in their essential features. An intercycle nucleolus consists of one or a few irregularly shaped particles that become more densely stained and condense into a knot at the beginning of each cycle. The knot unfolds into a necklace which beomes beaded as it elongates to a length of about 23 mum. Cells have one or two, rarely more, necklaces presumably depending on their ploidy. At the end of the cycle the necklaces contract, becoming coarser and fragmented before they condense to the intercycle condition of central irregular cores. Whereas nucleolar necklaces are a general response to hemolymph ecdysteroids, mitoses are locally determined and are imposed over other nuclear activities at any time in the third nucleolar cycle.     

Effect of DN-1417, a thyrotropin releasing hormone analog, on dopaminergic neurons in rat brain

Acute and chronic effects of γ-butyrolactone-γ-carbonyl-histidyl-prolinamide (DN-1417) were investigated on motor activity, dopamine (DA) metabolites and DA receptors in various brain regions of rats. The motor activity, as measured with Automex recorder, was enhanced after a single injection with DN-1417 (20 mg/kg, IP), and the motor stimulating action persisted during 21 daily injections. Acute DN-1417 elevated both homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in 7 brain regions, prefrontal cortex polar, medial and lateral fields, nucleus accumbens, olfactory tubercles, amygdala and striatum. After chronic treatment for 7 days, the acute effect of DN-1417 on DA metabolites disappeared in all regions except for the striatum in which DN-1417 still increased HVA and DOPAC. The response of striatal DA metabolites was also observed after chronic treatment for 21 days. Chronic DN-1417 produced no significant change in ³H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal ³H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment. These results indicate that DN-1417 interacts with mesocortical, mesolimbic and nigrostriatal DA systems in the different modes of action. The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons. The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested.     

Sensory projections to the nucleus basalis prosencephali of the pigeon

Summary The afferent pathways to the nucleus basalis prosencephali of the pigeon were studied by use of the horseradish peroxidase (HRP) technique. It was confirmed that this nucleus receives a direct pathway from the nucleus sensorius principalis nervi trigemini and that, as in the starling, it receives a direct input from the nucleus lemnisci lateralis, pars ventralis, an auditory relay. Totally novel is the finding that the nucleus basalis prosencephali is the target of a direct pathway originating in the medullary nucleus vestibularis superior. All three pathways bypass the thalamus. From within the telencephalon the nucleus basalis prosencephali also receives fibres from the tuberculum olfactorium and the peri-ectostriatal belt, suggestive of olfactory and visual input. Marked cell bodies were also found in the neostriatum frontolaterale. It is assumed that these arose from HRP uptake by axons of the tractus fronto-archistriatalis that course through the nucleus basalis prosencephali to the anterodorsal archistriatum. Marked fibres and bouton-like formations were observed in the latter structure. The afferents to the nucleus basalis prosencephali are discussed in conjunction with the probable role of the nucleus as a sensorimotor coordinator of the pecking/feeding behaviour of the pigeon.