Administration of transforming growth factor-alpha enhances anatomical and behavioral recovery following olfactory nerve transection

Although replacement of olfactory receptor neurons (ORNs) and subsequent reinnervation of the olfactory bulb occur following ORN injury, the intrinsic and extrinsic factors that contribute to the regulation of this dynamic process have not yet been fully identified. Recent research indicates that several growth factors have neurogenic effects on ORNs in vitro, and that chronic in vivo administration of either basic fibroblast growth factor, epidermal growth factor, or transforming growth factor-alpha (TGF-alpha) following chemical lesion can enhance the normal rate of ORN reinnervation of the olfactory bulb. The primary goal of the present experiments was to further assess the extent to which growth factor-related enhancements in the rate of anatomical recovery during ORN reconstitution and subsequent reinnervation of olfactory bulb are accompanied by enhancements in the rate of recovery of odor-guided behavior.A series of experiments in rats was conducted to initially characterize the time course of the anatomical and behavioral recovery normally observed following ORN reconstitution as a consequence of olfactory nerve transection, and to subsequently characterize the anatomical and behavioral effects of TGF-alpha administration on this normal rate of recovery. Consistent with a host of prior studies, olfactory nerve transection produced consistent and substantial deafferentation of olfactory bulb followed by a time-dependent anatomical recovery which was significantly enhanced by administration of TGF-alpha. The effect of TGF-alpha on functional recovery following olfactory nerve transection was also assessed using an odor-guided fear conditioning task. ORN lesioned animals receiving injections of TGF-alpha during recovery were found to display enhanced conditioned responding to an olfactory stimulus compared to untreated subjects. Further behavioral analyses suggested that this enhanced functional recovery was likely not due to non-specific effects of TGF-alpha on cognition or motor activity, but rather to enhanced olfactory input to the CNS.Future studies will likely reveal the exact mechanism of action mediating the anatomical and concomitant behavioral effects of this growth factor. Since ORNs are one of only a few populations of neurons capable of regeneration or replacement, the continued study of the cellular and molecular factors that coordinate this regenerative process may ultimately lead to the development of therapeutic strategies to promote an enhanced functional recovery following injury to other neuronal populations.     

An antidepressant mechanism of desipramine is to decrease tumor necrosis factor-alpha production culminating in increases in noradrenergic neurotransmission

The monoamine theory of depression proposes decreased bioavailability of monoamines, such as norepinephrine (NE), as the underlying cause of depression. Thus, the antidepressant efficacy of NE-reuptake inhibitors such as desipramine is attributed to increases in synaptic concentrations of NE. The time difference between inhibition of reuptake and therapeutic efficacy, however, argues against this being the primary mechanism. If desipramine elicits its therapeutic efficacy by increasing NE release, in turn, increasing activation of the alpha(2)-adrenergic autoinhibitory receptor, then mimicking this increase with an exogenous agonist (clonidine) should support or even enhance the efficacy of the antidepressant. Intriguingly, simultaneous administration of clonidine with desipramine prevented the cellular and behavioral effects elicited by desipramine alone, in both acute and chronic administration paradigms. These results suggest the involvement of additional factor(s) in the mechanism of antidepressant action of this drug. Desipramine administration results in a virtual ablation of neuron-derived tumor necrosis factor-alpha (TNF), thus implicating an essential role of TNF in the therapeutic efficacy of this antidepressant. Additionally, following chronic administration of desipramine, TNF-regulation of NE release is transformed, from inhibition to facilitation. Here, we demonstrate that a transformation in TNF-regulation of NE release in the brain is a key element in the efficacy of this antidepressant. Interestingly, an increase in neurotransmission prior to the antidepressant's effect on TNF production prevents the efficacy of the antidepressant drug. Thus, the efficacy of desipramine is due to decreased levels of TNF in the brain induced by this drug, ultimately modifying noradrenergic neurotransmission.     

Bulbectomy and sensitivity to estrogen: Anatomical and functional specificity

In order to clarify the influence of the olfactory system on female sexual behavior, ovariectomized rats were given sham operations (SHAM), total bilateral olfactory bulbectomy (TBULBX), partial bulbectomy (PBULBX), anterior olfactory nucleus lesions (AON) or accessory olfactory bulb lesions (AOB), and tested for lordosis behavior. Only TBULBX resulted in increased sensitivity to estradiol benzoate (EB) in that lordosis quotients (LQ) were increased and rejection behavior decreased following administration of 2, 4 or 8 μg EB/kg/day for 3 days. Only TBULBX group rats were anosmic on 2 postoperative tests. TBULBX group rats showed very mild hyperresponsiveness on an emotionality test. Effects of TBULBX on LQ are not due to general sensory hyperresponsiveness or EB-induced hyperresponsiveness since no differences in the quality of lordosis occurred, and no differences occurred in latency to paw-lift on hot plate tests with or without EB. Heightened EB sensitivity in the TBULBX group is not due to adrenal steroids since following adrenalectomy and 8 μg EB/kg treatment, TBULBX group LQ scores were still elevated relative to those of SHAM controls. The LQ scores of PBULBX group rats were intermediate to those of SHAM and TBULBX group rats. Bulbectomy-induced alterations in sensitivity to EB as measured by the LQ do not appear to be due to alterations in “arousal” mechanisms in general. While deficits in olfactory perception might exacerbate the effect, it is unlikely that anosmia per se is sufficient to induce major alterations in the degree of sexual receptivity following EB. The magnitude of behavioral effects of bulbectomy on EB sensitivity may be related, to some extent, to the amount of bulb tissue removed. It is possible that bulbectomy may enhance behavioral sensitivity to EB by disrupting biochemical responses to EB in limbic system structures which normally exert an inhibitory influence over sexual receptivity.     

Does intranasal application of zinc sulfate produce anosmia in the rat?

Transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from olfactory sensory neurons to the olfactory bulb as well as odor detection and discrimination were examined in rats in which each nasal epithelium had been irrigated with 0.1-0.5 ml 5% zinc sulfate. After treatment, rats showed few or no deficits in discriminating among odors and in detecting high (1%-0.01%) concentrations of ethyl acetate, but some had deficits in detecting lower concentrations of the odor. In most cases, HRP reaction product filled more than 30% of olfactory bulb glomeruli 2-4 days after treatment with ZnSO4. The behavioral outcomes are in agreement with recent reports of considerable savings in olfaction even after severe reduction of afferent projections to the olfactory bulb. We conclude that, in the rat, intranasal application of ZnSO4, as generally practiced, does not produce anosmia.     

Effects of chronically administered antidepressant drugs on animal behavior

We reviewed the literature about the effects of chronically administered antidepressant drugs on animal drive-related behaviors that are increased by platform REM Sleep Deprivation (RSD): intracranial self-stimulation, locomotion, aggression, feeding, grooming and sex. We found no previous review of behavioral effects of chronic antidepressant drugs; about 200 papers on behavioral effects of one dose of antidepressant drugs; and only 14 papers on behavioral effects of chronically administered antidepressant drugs. With one dose, antidepressant drugs usually did not increase animal behaviors. With chronic administration, antidepressant drugs increased intracranial self-stimulation, locomotion, and affective aggression. Chronic drug effects on feeding, grooming, and sex were not studied. These findings are consistent with the hypothesis that antidepressant drugs increase animal drive-related behaviors by RSD because RSD precedes tested behavior with chronic drug administration but not with one dose. The findings, plus a critical review of RSD by pendulum and by midbrain stimulation, support the hypotheses (1) that in animals all methods of RSD increase drive-related behaviors; and (2) that in humans antidepressant drugs improve depression by RSD which enhances such behaviors.     

Nisoxetine infusion into the olfactory bulb enhances the capacity for male rats to identify conspecifics.

In the present report, the norepinephrine uptake inhibitor nisoxetine as well as a cocktail of nisoxetine and the alpha-adrenergic receptor antagonist phentolamine were infused unilaterally into the olfactory bulb during microdialysis to assess their effects upon the capacity of male rats to identify conspecifics. A social discrimination test was conducted while simultaneously measuring olfactory bulb norepinephrine output in the dialysate before, during, and after behavioral testing. Nisoxetine significantly increased norepinephrine levels in the olfactory bulb compared with the Ringer's solution control group. Following such increases in olfactory bulb norepinephrine, identification responses were enhanced compared with that observed in the Ringer's control. In the presence of phentolamine, nisoxetine elevated olfactory bulb norepinephrine to levels similar to that obtained in the nisoxetine alone group, however, investigatory responses directed to the conspecifics indicated an absence of identification capacity similar to that observed in the Ringer's control group.These results reveal a direct link between norepinephrine transmission in the olfactory bulb and enhanced identification via its activation of postsynaptic alpha-adrenergic receptors. These results also show that inhibition of norepinephrine uptake may represent an important mechanism involved with the enhancement of social identification and suggest a possible novel effect for the antidepressant nisoxetine.     

Successful protection by amantadine hydrochloride against lethal encephalitis caused by a highly neurovirulent recombinant influenza A virus in mice

A mouse model system for a lethal encephalitis due to influenza has been established by stereotaxic microinjection with the recombinant R404BP strain of influenza A virus into the olfactory bulb of C57BL/6 mice. The virus infection spread selectively to neurons in nuclei of the broad areas of the brain parenchyma that have anatomical connections to the olfactory bulb, leading to apoptotic neurodegeneration. The inflammatory reaction at the extended stage of viral infection involved the vascular structures affected by induction of inducible nitric oxide synthase and protein nitration; those were related to the etiology of fatal brain edema. The intraperitoneal administration of amantadine inhibited the viral growth in the brain and saved mice from the lethal encephalitis. The severity of neuronal loss paralleled the time lag between the virus challenge and the start of amantadine treatment. Thus, early pharmacological intervention is essential to minimize neurological deficits due to influenza virus-induced neurodegeneration.     

Olfactory bulbectomy induces neuronal rearrangement in the entorhinal cortex in the rat

In humans, depression has been associated with disturbances in olfactory circuitry. Symptoms of depression can be mimicked in animals after olfactory bulbectomy (OBX). Animal models of depression-like behavior produce similar neuronal rearrangements in various brain regions as seen in patients affected by depression. We have recently observed that OBX produces neuronal hypotrophy in the piriform cortex (PirC) and CA1 hippocampus as well as decreased adult cell proliferation in the dentate gyrus (DG) of hippocampus. Thus we further evaluated the effects of OBX in neuronal arborization and spine density in brain regions involved in the control of circadian circle, emotion and memory processing such as the prefrontal cortex (PFC), nucleus accumbens (NAcc), infralimbic cortex (ILC), orbitolateral cortex (OLC) and entorhinal cortex (EC). Our present results show that along with severe behavioral deficits observed in these animals, OBX considerably decreased dendritic branching and the total dendritic length in the EC, a major interface of the hippocampus and neocortical regions. The remaining cortices and NAcc were not affected by OBX. Thus, we propose that the lack of input from the olfactory bulbs resulted in serial neuronal rearrangements in the PirC, EC, and hippocampus leading, at least partially, to behavioral deficits in emotion and memory processes.     

Spreading depression in the olfactory bulb of rats: reliable initiation and boundaries of propagation

Spreading depression in the olfactory bulb of rats is an elusive phenomenon, the demonstration of which requires specific conditioning procedures. The present paper describes a simple technique for reliable initiation of bulbar spreading depression with microinjections of potassium acetate. Adult hooded rats were anesthetized with pentobarbital (50 mg/kg) and slow potential changes accompanying spreading depression were recorded with capillary microelectrodes stereotaxically inserted into the olfactory bulb and adjacent forebrain structures. KCl microinjection (0.5-1.0 microliter, 0.134-0.670 mol/l) into the olfactory bulb elicited local depolarization which only exceptionally developed into a propagating spreading depression. Potassium acetate (0.5-1.0 microliter, 0.15 mol/l) injected into the rostral olfactory bulb evoked a negative slow potential wave (amplitude of around 25 mV and duration 30-50 s) propagating at a rate of 3-4 mm/min through all the olfactory bulb layers. Low positive (5 mV) instead of negative waves were recorded in the superficial olfactory nerve layer with reversal in the glomerular layer (200-300 micron). The slow potential decreased in the rostrocaudal direction and expired at the caudal boundary of the olfactory bulb. Bulbar spreading depression never spread to neocortex, and cortical spreading depression never entered into the olfactory bulb but stopped in the anterior olfactory nucleus 7 mm rostral to bregma. Repeated potassium acetate injections into the olfactory bulb occasionally elicited a series of spreading depression waves recurring at regular intervals, probably reflecting reverberation of scroll-shaped waves around the rostrocaudal axis of the olfactory bulb.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spatial coding of enantiomers in the rat olfactory bulb

Because of their unique properties, enantiomers (pairs of mirror-symmetric, nonsuperimposable molecules that differ only in optical activity and their interaction with other chiral molecules) have been instrumental in demonstrating that olfactory perception relies on molecular shape. To investigate how molecular structure is encoded by the olfactory system, we combined behavioral discrimination tasks with optical imaging of intrinsic signals. We found that rats can behaviorally discriminate members of a wide range of enantiomer pairs, and imaging revealed enantiomer-selective glomeruli in the olfactory bulb, indicating that the spatial pattern of glomerular activity provides sufficient information to discriminate molecular shape.     

Preserved sigma1 (sigma1) receptor expression and behavioral efficacy in the aged C57BL/6 mouse

The sigma(1) (sigma(1)) receptor represents a unique intracellular neuronal protein modulating several neurotransmitter responses with relevant effects on cognitive functions. We examined here its expression and behavioral efficacy during aging. The sigma(1) receptor expression was examined in young (2 months old) and aged (24 months old) C57BL/6 mouse brain using comparative RT-PCR and immunohistochemistry. The promnesic effect of PRE-084, a selective sigma(1) agonist, was assessed using a water-maze procedure. The sigma(1) mRNA expression was not affected during aging in the olfactory bulb, hippocampus, hypothalamus, cortex or cerebellum. The sigma(1) immunolabeling was intense in the olfactory bulb, hippocampus, hypothalamus and midbrain of the young mouse and the distribution appeared unchanged in the aged. The subcellular localization was similar in aged and younger animals, the protein being present on nuclear, mitochondrial, endoplasmic reticular and plasmic membranes. At the behavioral level, aged C57BL/6 mice showed deficits in the invisible platform learning, but not when the platform was visible. Animals subjected to a transfer test under repeated treatment with saline or PRE-084 significantly learned the new platform location. This study shows that sigma(1) receptor expression is preserved in aged animals and demonstrates the efficacy of a selective sigma(1) agonist against age-related memory deficits. Targeting this unique receptor may offer an original drug strategy during aging.     

Neurotrophic factors in the primary olfactory pathway

The number of identified growth factors continues to increase rapidly with many being implicated in the development of the nervous system, although for most of them the autocrine and paracrine pathways of cellular regulation still remain to be elucidated. The primary olfactory pathway, consisting of the olfactory epithelium and olfactory bulb, is presented here as a very useful model for the analysis of growth factor function. Review of the available literature suggests that a large proportion of neuroactive growth factors and their receptors are present in the olfactory epithelium or olfactory bulb. Furthermore, the primary olfactory pathway is one of the most plastic in the nervous system with neurogenesis continuing to contribute new sensory neurones in the olfactory epithelium and new interneurones in the olfactory bulb throughout adult life. The rich diversity of growth factors and their receptors in the olfactory system indicates that it will be useful in elucidating how these molecules regulate the formation of the nervous system. The olfactory epithelium in particular is proving useful as a model for the actions of growth factors in directing the neuronal lineage from stem cell to mature neurone.     

Brain transplants enhance rather than reduce the impairment of spatial memory and olfaction in bulbectomized rats

The possibility to compensate the loss of olfactory and non-olfactory functions due to removal of the olfactory bulb by embryonal brain grafts was investigated in adult rats. Spatial working memory was examined in an 8-arm radial water maze task 6 weeks after bulbectomy. During 15 daily trials, performance gradually improved in bulbectomized controls (n = 10) and in rats with olfactory bulb transplants (n = 9), but did not attain that of intact controls (n = 10). No improvement was observed in the rats with substantia nigra grafts (n = 8). Eleven weeks after bulbectomy, the same rats were tested in the water tank navigation task. The performance improved during ten 12-trial sessions in bulbectomized rats less than in intact controls, but more than in the transplanted rats. The olfactory food retrieval test performed 14 weeks after bulbectomy revealed almost full recovery of smell in bulbectomized rats, but not in the transplanted animals. It is concluded that the spatial memory deficit is probably due to bulbectomy-induced interference with septohippocampal function which is not alleviated, but rather enhanced by transplantation. The results suggest that the effect of brain grafting is not always beneficial.     

Behaviour and hormonal status in healthy rats on a diet rich in Maillard reaction products with or without solvent extractable aroma compounds

Maillard reaction products (MRPs) are generated upon thermal processing of foods, modifying their colour and flavour. We asked whether aroma compounds generated via Maillard-type reactions modulate the in vivo effects of MRP-rich diets (MRPD). Male Wistar rats were fed for 3weeks either with a standard rat chow, an aroma compounds containing MRPD comprising 25% bread crust, or an aroma-extracted MRPD. In contrast to standard rat chow, consumption of MRPDs affected glucose control, induced hyper-leptinemia and hyper-adiponectinemia. Plasma adipokines were significantly higher in rats on aroma containing MRPD in comparison with those consuming aroma-extracted MRPD. Consumption of both MRPDs significantly increased the expression of the insulin receptor in the olfactory bulb, and mildly in the hypothalamus. Administration of the aroma containing MRPD significantly increased the leptin receptor expression in the olfactory bulb, and in the hypothalamus. Under both MRPDs, strong expression of c-fos indicated an increased neuronal activity in the olfactory bulb. Neuronal activity in brain areas involved in the central regulation of food intake and energy homeostasis was more pronounced in rats fed by the aroma containing MRPD. In conclusion, short-term consumption of a MRPD fortified with bread crust, particularly if containing solvent extractable volatile aroma compounds, affected the leptin-induced central signalling of anorexigenic/orexigenic hormones, and the neuronal activity in the central nervous system. Behavioural changes and altered glucose control were more evident in rats on the aroma containing MRPD. Our data suggest that volatile aroma compounds in foods might affect endocrine signalling and neuronal regulation of metabolism.     

Is drug-placebo difference in short-term antidepressant drug trials on unipolar major depression much greater than previously believed?

A pooled analysis of randomized placebo-controlled short-term antidepressant trials on unipolar major depression shows that the rate of antidepressant and placebo responders is 50% and 30% respectively. The traditional calculation of antidepressant–placebo difference (50–30 = 20%) in these drug trials is based on the assumption that all placebo responders should be antidepressant responders, a postulation that has been never investigated and proved. Further studies are needed investigating directly the relationship of placebo response in relation to antidepressant response/nonresponse. If a substantial part of placebo responders were antidepressant nonresponders, the drug–placebo differences in all short-term antidepressant drug trials on unipolar major depression are much more than 20%, and the previously published data on antidepressant–placebo difference should be re-calculated.     

Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits.     

Elucidation of the neurobiology of depression: insights from a novel genetic animal model

Development of drugs for the effective treatment of depressive disorders requires elucidation of factors that are critical for clinically antidepressant effects. During the past 4 years, we have studied in situ neurochemical alterations in the brain that may underlie depressive behavior. This was achieved using the genetically-selected Flinders Sensitive Line (FSL) of rats (a unique animal model of depression), before and after chronic antidepressant treatment. This line of rats exhibits behavioral features characteristic of depression, and responds to chronic, but not acute, antidepressant treatments. This review summarizes our findings concerning the local neuro-dynamics in the brain during manifestation of depressive behavior and effective antidepressant treatment in this animal model of depression. Understanding the abnormalities manifested in neurochemical pathways during depressive disorders and the dynamic effects of these abnormalities on the onset of action and efficacy of pharmacological treatments are crucial for the development of effective antidepresssant drugs and therapeutic strategies.     

升麻苷H-1利用鼻腔嗅觉区鼻-脑通道进行鼻脑靶向给药的可行性

BACKGROUND: Recent studies have suggested that intranasal administration is one of the ways to target drug  delivery, and can effectively make the drug that cannot pass through the blood brain barrier by other pathways to bypass the blood brain barrier, resulting in targeted delivery to the brain. It provides a promising route for the treatment of central nervous system diseases. OBJECTIVE: To study the pharmacokinetic and brain-targeted channel-tropism tissue distribution character of cimicifugoside H-1 after nasal and intravenous administration in plasma and tissues in rats, in order to evaluate the feasibility of developing brain-targeted nasal delivery system of cimicifugoside H-1 by the passage between nose and brain in nasal olfactory area. METHODS: After intravenous injection and nasal administration of cimicifugoside H-1, the drug concentrations of plasma and channel-tropism organs (lung, spleen, stomach, large intestine, liver, kidney, brain, brain, cerebellum, cerebrospinal fluid, olfactory bulb and olfactory region) were detected. Drug-time curve was drawn. DAS program was used to select apartment model and pharmacokinetics parameters. RESULTS AND CONCLUSION: (1) The pharmacokinetics characters of cimicifugoside H-1 are rapidly absorbed and extensively distribution. Among major channel-tropism organs, drug concentrations were higher in the lung and brain than in the other organs. (2) Cimicifugoside H-1 could be straightly transported into brain by the intranasal administration. The molecule through olfactory mucosa in nasal cavity entered into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, cerebrospinal fluid, cerebrum and cerebellum gradually. Olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. (3) Compared with the intravenous injection, cimicifugoside H-1 through the intranasal administration has a significant channel-tropism of lung and brain targeting.       

微囊化异种嗅球组织移植联合药物干预修复受损脊髓的研究

目的:研究微囊化异种嗅球组织移植联合β-七叶皂甙钠对脊髓继发性损伤的治疗保护作用及机制。方法:健康SD大鼠180只,随机分为损伤对照组、微囊化兔嗅球组织移植组、微囊化兔嗅球组织移植联合β-七叶皂甙钠治疗组,损伤组又设1、3、7、14、28d5个时相点,紫外分光光度计检测脊髓伊文氏蓝含量;免疫组织化学观察血管内皮生长因子(VEGF)的表达;神经功能评分法(BBB法)评价大鼠术后运动功能的恢复情况。结果:脊髓损伤后脊髓伊文氏蓝含量增加、VEGF表达下调,大鼠的运动功能缺失,经微囊化异种嗅球组织移植联合β-七叶皂甙钠治疗后血脊髓屏障的通透性有所改善,VEGF表达上调,大鼠的运动功能有所恢复。结论:微囊化异种嗅球组织移植对脊髓继发性损伤有较好的疗效,联合应用嗅球组织细胞和β-七叶皂甙钠在脊髓损伤修复治疗中具有协同作用。     

GDNF、GFAP和NGFRp75在成年大鼠和金黄地鼠嗅球成鞘细胞的免疫组织化学研究

目的　研究GDNF在成年大鼠和金黄地鼠嗅球成鞘细胞的表达 ,探索成鞘细胞在中枢神经再生中的作用。　方法　用免疫组织化学ABC法 ,显示GDNF在成年大鼠和金黄地鼠嗅球成鞘细胞的表达和分布 ,同时用NGFRp75和GFAP染色作为阳性对照。　结果　在成年大鼠和金黄地鼠嗅球的纤维层和小球层内均可见深棕色的GDNF免疫组织化学反应的成鞘细胞。在小球层与纤维层分界处和小球层与分子层分界处及嗅小球之间密集分布 ,在嗅小球之内较稀疏。同时在同一嗅球组织的另两组切片的相同部位 ,分别出现GFAP和NGFRp75免疫反应性细胞 ,间接说明GDNF免疫反应的结构是嗅球成鞘细胞。　结论　嗅球成鞘细胞含有胶质细胞源性神经营养因子