Sex differences in nerve growth factor levels in superior cervical ganglia and pineals

The current studies were undertaken to determine whether males or neonatally testosterone-treated rats of either gender have elevated endogenous levels of NGF in the SCG and one of its targets, the pineal gland. The ages studied were 5 days postnatal, which is at the peak of normal neuron death in the SCG but before a significant gender difference is present; 15 days, when normal neuron death is largely complete and males have more SCG neurons than females; and 30 days, when target innervation has matured.

At 5 days, while neuron death is occurring, but before there is a significant gender difference in neuron number in the SCG, pineal glands and SCGs of males had higher NGF content than those of females. The increased NGF in the ganglia of males at the time that these neurons are undergoing neuron death may play a role in the development of the sex difference in SCG neuron numbers. At 15 days, females had more NGF in their pineal glands and SCGs than did males, even though males have significantly more SCG neurons at this age than do females. This gender difference in the developmental course of NGF content could promote the survival of different populations of neurons in males and females. By 30 days, SCG and pineal NGF content of males was almost twice that of females. This is consistent with the presence of more neurons in the SCGs of males at this age.

Both the pineal gland and the SCG showed a loss of approximately 80% content of NGF during the first postnatal month. In males, this loss occurred between postnatal days 5 and 15, while in females, the drop in NGF content occurred between postnatal days 15 and 30. Treatment with testosterone from birth reduced NGF content in the SCGs of both males and females at 5 days of age. The depression of NGF levels by testosterone treatment may reflect a further acceleration of the developmental fall of NGC levels.     

Regulation of myelinated nociceptor function by nerve growth factor in neonatal and adult rats

The role of nerve growth factor (NGF) as a survival factor for sensory neurons during embryonic life has been well documented. Here we examine the actions of NGF or antisera against NGF (anti-NGF) on physiologically identified sensory neurons with myelinated axons later in life, after the dependence on NGF for survival ends. We find that the effects of NGF and anti-NGF are specific for sensory neurons which are nociceptors. Treatments were found to affect the biophysical properties, the development, or the physiological function of myelinated nociceptors. They also affect the animal's behavioral response to noxious stimulation, depending upon when the treatments were given: neonatally, from 2–5 weeks of age, or chronically, beginning at birth. Thus, we find that the actions of NGF are specific for nociceptors but that the function of this neurotrophic factor changes according to the developmental age of the animal.     

Destruction of sympathetic and sensory neurons in the developing rat by a monoclonal antibody against the nerve growth factor (NGF) receptor

The ability of the monoclonal antibody, 192-IgG, directed against the rat nerve growth factor (NGF) receptor to mimic or inhibit the actions of NGF was examined in vitro and in vivo. 192-IgG had no effect on morphology, survival, or protein synthesis rates of sympathetic neuronal cultures. When injected into newborn rats, destruction of sympathetic, but not sensory, neurons was produced. Injection prenatally produced more dramatic destruction of sympathetic neurons and, in addition, destruction of neural crest-derived sensory neurons. Therefore, although 192-IgG had no discernible effects in vitro, it produced a pattern of neuronal destruction in vivo qualitatively similar to that produced by antibodies to NGF itself.     

Covalent attachment of 125I-beta nerve growth factor to its receptors on sympathetic neurons

When 125I-beta nerve growth factor binds to sympathetic and sensory neurons, some labeled ligand is sequestered (becomes inaccessible to the external milieu) in a time- and energy-dependent manner. It would appear that the higher affinity receptor (type I) participates in this process to a greater extent than does the lower affinity receptor (type II) [ Olender and Stach , 1980; Olender et al., 1981]. A small portion of the sequestered 125I-beta nerve growth factor is found as part of a high molecular weight complex. When cells, which have been incubated with 125I-beta nerve growth factor, are solubilized with Triton X-100 and subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, a complex with an apparent molecular weight of approximately 240,000 is obtained. The formation of the covalent complex can be prevented by the prior addition of excess unlabeled beta nerve growth factor or sodium fluoride and dinitrophenol. The covalent 125I-beta nerve growth factor-receptor complex is dissociated in 50 mM dithiothreitol indicating that disulfide linkages are involved. At concentrations of beta nerve growth factor (3.8 X 10(-11) -3.8 X 10(-10) M) where maximal fiber outgrowth occurs in vitro, approximately 50-266 attomoles (0.3-1.6% of the type I receptors) of the covalent complex are formed per 10(7) nerve cells. These data suggest that a small portion of the 125I-beta nerve growth sequestered by sympathetic neurons becomes covalently attached to its receptor subsequent to its sequestration in a manner which appears to involve type I receptors.     

人NGF促进感觉神经生长和诱导SP释放实验研究

目的采用体外模型对比研究观察,评估人痛性椎间盘细胞外基质对小鼠背根神经节神经轴突生长所产生的促进作用和神经肽（sP）的诱导作用。方法通过获取椎间盘源性下腰痛患者的椎间盘组织（退变组）,以及正常人腰椎间盘组织（正常组）提取细胞基质,对小鼠背根神经节神经元（DRG）进行培养,通过形态学观察神经元轴突生长和酶联免疫吸附法（ELISA）检测SP含量。结果实验组神经生长因子（NGF）浓度显著高于正常组;实验组神经元轴突平均长度为（134．17±2．21）μm,明显高于正常组的（121．28±4．10）μm,二者相比有明显差异性（P〈0．05）。在退变人椎间盘组织培养液中SP物质比率明显高于正常组（P〈0．001）,二者具有显著性差异。结论人退变椎间盘细胞外基质中高表达的NGF能促进感觉神经轴突的生长以及诱导和疼痛相关神经肽的释放。     

Neuronal preservation in the sympathetic ganglia of rats with chronic streptozotocin-induced diabetes

Recent studies have reported that rat sympathetic neurons exposed to increased concentrations of glucose in vitro initiate an apoptotic program which culminates in neuronal cell death, a process proposed to contribute to the development of human diabetic autonomic neuropathy. We tested this hypothesis in an in vivo streptozotocin model of diabetic autonomic neuropathy using an unbiased counting method to quantitate neuron numbers in control and diabetic rats. Ten months of severe untreated diabetes failed to produce significant neuron loss in either the rat superior mesenteric or superior cervical sympathetic ganglia indicating that apoptotic neuronal cell death is unlikely to play a role in the pathogenesis of experimental diabetic autonomic neuropathy.     

Time and dose dependencies of effects of nerve growth factor on sympathetic and sensory neurons in neonatal rats

Nerve growth factor (NGF) plays a role in the development of several components of the sympathetic and sensory nervous systems. The objectives of this study were to examine the time and dose dependencies of some of the well known effects of NGF on sympathetic ganglia and to examine qualitatively and quantitatively the recently described effects on sensory ganglia of neonatal rats. Single doses of NGF as low as 0.1 mg/kg produce increases in tyrosine hydroxylase (TOH) activity in superior cervical ganglia (SCG), and doses of 3 mg/kg produce maximal effects. Larger doses and longer treatments are required to see increases in protein content of the SCG. Larger doses are also required to affect TOH activity in the adrenal gland. Increases in TOH activity in SCG can be observed within 18 h of injection. Chronic NGF treatment for three weeks produces no change in blood pressure or heart rate in neonatal rats. Chronic administration of NGF (1 or 3 mg/kg/day) results in dose-related increases in the protein content of dorsal root ganglia (DRG). The increase in protein content of the DRG was associated with an increase in the diameter of smaller neurons (those<30 μm in diameter), but NGF caused no change in the number of neurons.     

A re-evaluation of the effects of gonadal steroids on neuronal activity in the male rat

Single unit activity (SUA) was recorded from 77 cells located in the arcuate nucleus (ARC) and medial preoptic area (MPA) of anesthetized, intact male rats. Animals were administered vehicle, testosterone (T; 5 or 50 μg) or 17β-estradiol (E; 0.5 μg) intravenously and SUA was monitored for 8–12 min. T (50 μg) reduced SUA in 50% of ARC units and 44% of MPA units within 2.1 ± 0.46 and 3.3 ± 0.92 min, respectively. Inhibition of ARC SUA was more pronounced than MPA SUA. A small percentage (9%) of ARC units were excited by T. E reduced SUA in 29% of ARC units and 27% of MPA units. Single doses of 5 Mg T did not affect ARC activity. However, when followed within 10 min by an additional dose of 5 or 50 μg T, 30% and 43% of ARC units were inhibited, respectively. Doses (10 μg) of T produced plasma T concentrations within physiological limits, although 50 μg doses produced supraphysiological T levels. Neither dose affected circulating LH concentrations. We conclude that physiological and supraphysiological concentrations of T can rapidly affect SUA within the ARC.     

Roles of sex and gonadal steroids in mammalian pheromonal communication

A brain circuit (the accessory olfactory system) that originates in the vomeronasal organ (VNO) and includes the accessory olfactory bulb (AOB) plus additional forebrain regions mediates many of the effects of pheromones, typically comprised of a variety of non-volatile and volatile compounds, on aspects of social behavior. A second, parallel circuit (the main olfactory system) that originates in the main olfactory epithelium (MOE) and includes the main olfactory bulb (MOB) has also been shown to detect volatile pheromones from conspecifics. Studies are reviewed that point to specific roles of several different steroids and their water-soluble metabolites as putative pheromones. Other studies are reviewed that establish an adult, ‘activational’ role of circulating sex hormones along with sex differences in the detection and/or processing of non-steroidal pheromones by these two olfactory circuits. Persisting questions about the role of sex steroids in pheromonal processing are posed for future investigation.     

Effects of nerve growth factor on the survival of primary cultured adult and aged mouse sensory neurons

This study investigated the effects of exogenous nerve growth factor (NGF) on the survival and differentiation in primary culture of sensory neurons isolated from adult (6 months) and aged (2 years) mice. For neurons prepared from adult mice, a concentration effect was evident during a 2 week culture period: Neuronal counts in cultures supplemented with 25 and 50 ng/ml NGF did not differ significantly from those of control cultures without exogenous NGF or those with anti-NGF included in the culture medium, whereas cultures supplemented with either 100 or 200 ng/ml NGF contained higher numbers of neurons throughout the culture period. Cultures prepared from aged mice contained less neurons than those from adult mice, although those supplemented with 100 ng/ml NGF retained higher neuronal numbers than cultures from aged mice which did not receive exogenous NGF. Neuronal diameters were measured to investigate whether specific subpopulations of neurons were more dependent on NGF; the results indicate that neurons of a medium-larger diameter were more prevalent than cells with a smaller diameter following NGF administration. A shape index was calculated for each culture regimen; with longer culture periods a higher proportion of spindle-shaped neurons was observed. © 1993 Wiley-Liss, Inc.     

Nerve growth factor receptor immunoreactivity in the neuronal perikarya of human sensory and sympathetic nerve ganglia

We examined immunohistochemically the dorsal root ganglia, sympathetic ganglia, spinal cord, ventral and dorsal roots, and sciatic nerves obtained at autopsy from adult humans, using a monoclonal antibody against the human nerve growth factor receptor. We observed labelling in a granular pattern in the neuronal perikarya of dorsal root and sympathetic nerve ganglia. Ventral horn cells and axons were not labelled.     

Galanin-like immunoreactivity in capsaicin sensitive sensory neurons and ganglia

In rats treated with capsaicin (CAP) as neonates, galanin-like (GA) immunoreactivity is markedly decreased in the trigeminal ganglion and the dorsal root ganglia as well as in the superficial layers of the dorsal spinal cord (laminae I and II), the substantia gelatinosa, the nucleus and tractus of the spinal trigeminal nerve and the nucleus commissuralis. Since CAP causes selective degeneration of primary sensory neurons of the C-fiber type and type B-cells of sensory ganglia, it is concluded that GA in CAP-sensitive primary sensory neurons represents a novel peptidergic system possibly involved in the transformation or modulation of peripheral nociceptive impulses. This system differs from the CAP-resistant GA-like neurons in other brain areas.     

Effects of nerve growth factor on the survival and synaptic function of Ia sensory neurons axotomized in neonatal rats

Sensory neurons with small diameters (A delta and C cells) are known to be responsive to exogenous NGF even at postnatal stages. We have examined whether large Group Ia sensory neurons (A alpha cells) arising from muscle spindles are also responsive to NGF in neonatal rats. For this purpose, monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in spinal motoneurons by Group Ia muscle afferent volleys. When a muscle nerve was crushed on the day after birth, the monosynaptic EPSPs elicited by afferent volleys from the muscle were depressed within several weeks. This synaptic depression was partially reversed by daily treatment with NGF. NGF treatment also enhanced the EPSPs evoked by stimulation of intact muscle nerves, but this effect was less marked than that on the EPSPs produced by stimulation of the previously crushed muscle nerve. Exogenous NGF was effective for the EPSPs when the treatment began on the day after birth but not when the treatment began 4 d after birth. Following crush of a muscle nerve on the day after birth, about 45% of the sensory neurons derived from the muscle were lost. The cell death of small sensory neurons was prevented by daily treatment with NGF, whereas the NGF treatment was ineffective in preventing the cell death of large sensory neurons. The results indicate that Group Ia sensory neurons are responsive to NGF during early postnatal life.     

Effect of injury on nerve growth factor uptake by sensory ganglia

The level of the nerve growth factor protein, NGF, in vivo has a profound influence on axonal sprouting by sensory neurons of vertebrate dorsal root ganglia. There is evidence also that NGF may play similar roles in cholinergic central structures in brain. In both instances, retrograde transport of NGF has been demonstrated. Here we examined uptake of NGF by DRG neurons in response to contusion injury of the spinal cord. Under these conditions there was uptake and transport of NGF into large DRG neurons via central processes but no uptake by non-DRG central neurons. Thus, any effects of NGF on spinal neurons or their processes would be secondary to the direct effects of NGF on DRG neurons.     

Different effects of nerve growth factor on cultured sympathetic and sensory neurons

Long-term cultures of dissociated nodose ganglion (NG) and superior cervical ganglion (SCG) neurons from newborn rabbits were used to compare their response to nerve growth factor (7S NGF). SCG neurons required added NGF for their survival and a concentration of 1 μg/ml was found to be optimal. NG neurons, on the other hand, survived well for a long term without addition of NGF, but its application (1 μg/ml) was found to be effective in accelerating the growth of fibers (neurites) and neuronal somata. It is concluded that unlike SCG, NG neurons do not depend on exogenous NGF but may require an intrinsic trophic-like factor which may be contained in the serum of the medium, emanating from glial cells or by metabolic cooperation between neurons.     

Sex steroids and connectivity in the human brain: a review of neuroimaging studies

Our brain operates by the way of interconnected networks. Connections between brain regions have been extensively studied at a functional and structural level, and impaired connectivity has been postulated as an important pathophysiological mechanism underlying several neuropsychiatric disorders. Yet the neurobiological mechanisms contributing to the development of functional and structural brain connections remain to be poorly understood. Interestingly, animal research has convincingly shown that sex steroid hormones (estrogens, progesterone and testosterone) are critically involved in myelination, forming the basis of white matter connectivity in the central nervous system. To get insights, we reviewed studies into the relation between sex steroid hormones, white matter and functional connectivity in the human brain, measured with neuroimaging. Results suggest that sex hormones organize structural connections, and activate the brain areas they connect. These processes could underlie a better integration of structural and functional communication between brain regions with age. Specifically, ovarian hormones (estradiol and progesterone) may enhance both cortico-cortical and subcortico-cortical functional connectivity, whereas androgens (testosterone) may decrease subcortico-cortical functional connectivity but increase functional connectivity between subcortical brain areas. Therefore, when examining healthy brain development and aging or when investigating possible biological mechanisms of 'brain connectivity' diseases, the contribution of sex steroids should not be ignored.     

Comparative studies on the effect of the nerve growth factor on sympathetic ganglia and adrenal medulla in newborn rats

The effect of nerve factor (NGF) and nerve growth factor antiserum (NGF-AS) on sympathetic ganglia and adrenal chromaffin cells of newborn rats was investigated in a comparative study.