Cavernous nerve injury elicits GAP-43 mRNA expression but not regeneration of injured pelvic ganglion neurons

Recovery of erectile dysfunction after cavernous nerve injury takes a long period. To elucidate this mechanism, unilateral cavernous nerve of male rat was cut, and the expression level of a nerve regeneration marker, the growth associated protein-43 (GAP-43) mRNA was evaluated by in situ hybridization and RT-PCR. While GAP-43 mRNA expression was transiently increased in the injured neurons of the major pelvic ganglion (MPG) at 7 days after nerve injury, continuous increase of GAP-43 mRNA was observed in the contralateral MPG from 7 days to 6 months after the nerve injury. Histochemical double-labeling studies for either neuronal NOS (nNOS) or tyrosine hydroxylase (TH) and the GAP-43 mRNA expression demonstrated that in injured MPG the transient up-regulation of GAP-43 mRNA was mainly seen in nNOS negative and/or TH positive neurons, suggesting non-parasympathetic post-ganglionic neurons, and also demonstrated that in contralateral MPG GAP-43 mRNA positive neurons were gradually increased in nNOS positive but TH negative neurons, suggesting parasympathetic post-ganglionic neurons. When a retrograde tracer Fluorogold (FG) was injected into the penile crus 7 days before histological experiments, FG-positive neurons were, if any, hardly seen in nNOS-positive neurons of the injured MPG for at least 6 months, whereas numerous FG-positive cells were seen in nNOS-positive neurons of the contralateral MPG. These results suggest that post-ganglionic projecting neurons of the intact side, which express increased GAP-43 mRNA, would be most likely to contribute to the recovery of the erectile function after unilateral cavernous nerve injury possibly by a plastic change such as nerve sprouting.     

Immunocytochemical analysis of [Met5]enkephalin-Arg6-Gly7-Leu8 immunoreactive structures in the rat superior cervical ganglion

Indirect immunofluorescence and immunoelectron microscopy were employed to analyze the enkephalinergic systems in the rat superior cervical ganglion (SCG). These systems were identified using specific antiserum against [Met5]Enkephalin-Arg6-Gly7-Leu8 (ENK-8), a peptide which is derived only from proenkephalin A. Abundant ENK-8 like immunoreactive (ENK-8-LI) neurons and fibers were observed in the SCG, but their distribution patterns were heterogenous; ENK-8-LI neurons were localized preferentially in the caudal two-thirds of the SCG, while immunoreactive fibers were found to be distributed more densely in the rostral one-third than in the remaining part of the SCG. Most of the ENK-8-LI neurons were large and had ultrastructural features resembling those of principal cells, some were identified electron microscopically as small intensely fluorescent (SIF) cells. ENK-8-LI fibers were varicose in appearance and surrounded the perikarya of neurons. Since most of these fibers were not detected after experimental decentralization of the SCG and since ENK-8-LI terminals were seen to contain small lucent vesicles, most of the former were thought to be preganglionic fibers. Immunoreactive fibers mainly formed synaptic contacts with the dendrites of non-immunoreactive principal cells, but a small proportion of ENK-8-LI principal cells also received synaptic input from them. Occasionally, immunoreactive fibers formed synapses with the processes or the soma of both ENK-8-LI and non-immunoreactive SIF cells. On the basis of these findings, we conclude that: (1) preganglionic ENK-8-LI fibers terminate mainly on the principal cells, which are devoid of ENK-8-LI structures; (2) the majority of ENK-8-LI neurons are principal cells, while the remainder are SIF cells; (3) inputs to these cells mainly involve structures lacking ENK-8 immunoreactivity; and (4) there are, however, a small number of ENK-8-LI preganglionic fibers which terminate on ENK-8-LI principal cells and SIF cells.     

Immunocytochemical analysis of [Met]enkephalin-Arg-Gly-Leu immunoreactive structures in the rat superior cervical ganglion

Indirect immunofluorescence and immunoelectron microscopy were employed to analyze the enkephalinergic systems in the rat superior cervical ganglion (SCG). These systems were identified using specific antiserum against [Met⁵]Enkephalin-Arg⁶-Gly⁷-Leu⁸ (ENK-8), a peptide which is derived only from proenkephalin A. Abundant ENK-8 like immunoreactive (ENK-8-LI) neurons and fibers were observed in the SCG, but their distribution patterns were heterogenous; ENK-8-LI neurons were localized preferentially in the caudal two-thirds of the SCG, while immunoreactive fibers were found to be distributed more densely in the rostral one-third than in the remaining part of the SCG. Most of the ENK-8-LI neurons were large and had ultrastructural features resembling those of principal cells, some were identified electron microscopically as small intensely fluorescent (SIF) cells. ENK-8-LI fibers were varicose in appearance and surrounded the perikarya of neurons. Since most of these fibers were not detected after experimental decentralization of the SCG and since ENK-8-LI terminals were seen to contain small lucent vesicles, most of the former were thought to be preganglionic fibers. Immunoreactive fibers mainly formed synaptic contacts with the dendrites of non-immunoreactive principal cells, but a small proportion of ENK-8-LI principal cells also received synaptic input from them. Occasionally, immunoreactive fibers formed synapses with the processes or the soma of both ENK-8-LI and non-immunoreactive SIF cells. On the basis of these findings, we conclude that: (1) preganglionic ENK-8-LI fibers terminate mainly on the principal cells, which are devoid of ENK-8-LI structures; (2) the majority of ENK-8-LI neurons are principal cells, while the remainder are SIF cells; (3) inputs to these cells mainly involve structures lacking ENK-8 immunoreactivity; and (4) there are, however, a small number of ENK-8-LI preganglionic fibers which terminate on ENK-8-LI principal cells and SIF cells.     

Growth-associated protein-43 (GAP-43) in the regenerating periodontal Ruffini endings of the rat incisor following injury to the inferior alveolar nerve

Alterations in the levels of growth-associated protein 43 (GAP-43)-like immunoreactivity (-LI) were examined in the lingual periodontal ligament of the rat incisor following two types of injury (resection and crush) to the inferior alveolar nerve (IAN). In normal animals, GAP-43-like immunoreactive (IR) structures were observed as tree-like ramifications in the alveolar half of the lingual periodontal ligament of incisors. Under immunoelectron microscopy, GAP-43-LI appeared in the Schwann sheaths associated with periodontal Ruffini endings; neither cell bodies of the terminal Schwann cells nor axonal profiles showed GAP-43-LI. During regeneration of the periodontal Ruffini endings following resection of the IAN, GAP-43-LI appeared in the cytoplasm of the terminal Schwann cell bodies and axoplasm of the terminals. The distribution of GAP-43-LI in the Ruffini endings returned to almost normal levels on days 28 and 56 following the injury. The changes in the distribution of GAP-43-LI following the crush injury were similar to those following resection; however, expression of GAP-43-LI was slightly higher for the entire experimental period compared with the resection. The transient expression of GAP-43 in the terminal Schwann cells and axonal profiles of the periodontal Ruffini endings following nerve injury suggests that GAP-43 is closely associated with axon–Schwann cells interactions during regeneration.     

On the Distribution of GAP-43 and its Relation to Serotonin in Adult Monkey and Cat Spinal Cord and Lower Brainstem

By use of a monoclonal antibody, the distribution of growth-associated protein (GAP)-43-like immunoreactivity (LI) has been studied in the spinal cord of adult grey monkeys ( Macaca fascicularis ) and adult cats by use of immunofluorescence and peroxidase-antiperoxidase techniques. The brainstem was also studied with in situ hybridization histochemistry. In both monkeys and cats, a dense innervation of GAP-43-immunoreactive (IR) fibres was seen in close apposition to large cell bodies and their processes in the motor nucleus of the ventral horn. Double-labelling experiments revealed a high degree of coexistence between GAP-43- and 5-hydroxytryptamine (5-HT, serotonin)-LI in the monkey motor nucleus, while in the cat no such colocalization could be verified. At the electron microscopic level, GAP-43 labelling was seen as a coating of vesicles and axolemma inside the terminals. In both monkey and cat, cell bodies expressing mRNA encoding GAP-43 were demonstrated in the medullary midline raphe nuclei. A similar location was also encountered for mRNA for aromatic l -amino acid decarboxylase, an enzyme found in both catecholamine- and serotonin-containing neurons. The present results suggest that GAP-43 is present in the 5-HT bulbospinal pathway of the monkey. In the cat, GAP-43 mRNA-expressing cell bodies were demonstrated in areas where descending 5-HT neurons are located, but no convincing colocalization of 5-HT- and GAP-43-LI was found at spinal cord levels, despite the existence of extensive fibre networks containing either of the two compounds. Possible explanations for this species discrepancy are discussed. The function of GAP-43 in nerve terminals impinging on the motoneurons is unknown. However, it may play a role in transmitter release and/or plasticity, since such roles have been proposed for this protein in other systems.     

Expression of GAP-43 and SCG10 mRNAs in lateral geniculate nucleus of normal and monocularly deprived macaque monkeys.

We performed nonradioactive in situ hybridization histochemistry (ISH) in the lateral geniculate nucleus (LGN) of the macaque monkey to investigate the distribution of mRNA for two growth-associated proteins, GAP-43 and SCG10. GAP-43 and SCG10 mRNAs were coexpressed in most neurons of both magnocellular layers (layers I and II) and parvocellular layers (layers III-VI). Double-labeling using nonradioactive ISH and immunofluorescence revealed that both GAP-43 and SCG10 mRNAs were coexpressed with the alpha-subunit of type II calcium/calmodulin-dependent protein kinase, indicating that both mRNAs are expressed also in koniocellular neurons in the LGN. We also showed that GABA-immunoreactive neurons in the LGN did not contain GAP-43 and SCG10 mRNAs, indicating that neither GAP-43 nor SCG10 mRNAs were expressed in inhibitory interneurons in the LGN. GABA-immunoreactive neurons in the perigeniculate nucleus, however, contained both GAP-43 and SCG10 mRNAs, indicating that both mRNAs were expressed in inhibitory neurons in the perigeniculate nucleus, which project to relay neurons in the LGN. Furthermore, to determine whether the expression of GAP-43 and SCG10 mRNAs is regulated by visual input, we performed nonradioactive ISH in the LGN and the primary visual area of monkeys deprived of monocular visual input by intraocular injections of tetrodotoxin. Both mRNAs were downregulated in the LGN after monocular deprivation for 5 d or longer. From these results, we conclude that both GAP-43 and SCG10 mRNAs are expressed in the excitatory relay neurons of the monkey LGN in an activity-dependent manner.     

Compensatory changes in contralateral sympathetic neurons of the superior cervical ganglion and in their terminals in the pineal gland following unilateral ganglionectomy

The sympathetic noradrenergic neurons of the rat superior cervical ganglia (SCGs) provide the major source of innervation to the pineal gland. The present study sought to determine if this sympathetic innervation can undergo collateral sprouting following partial denervation of the pineal by unilateral removal of the SCG (ganglionectomy), and whether such growth of axon terminals is associated with biochemical changes in the contralateral SCG. In the pineal gland following partial denervation, residual noradrenergic terminals underwent compensatory changes indicative of collateral sprouting, as evidenced by: a rapid reduction in tyrosine hydroxylase (TH) activity and in [3H]norepinephrine (NE) uptake, to about 50% of control by 2 days, which was followed by a gradual but sustained increase to levels of approximately 80% of control by 10 days and a reduction in the intensity and density but not in the distribution of fibers containing NE-induced fluorescence by 2 days, which was followed by a sustained increase. In the contralateral SCG, choline acetyltransferase (CAT) activity, a marker of cholinergic preganglionic terminals, was transiently increased to about 115% of control by 4 days and returned to control levels by 14 days after unilateral ganglionectomy; later, TH activity in noradrenergic cell bodies was gradually increased to about 140% of control by 10 days where it remained for up to 52 days. Unilteral ganglionectomy combined with decentralization of the contralateral SCG by preganglionic nerve cut prevented the compensatory changes in noradrenergic nerve terminals within the pineal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noradrenergic neurons expressing substance P receptor (NK1) in the locus coeruleus complex: a double immunofluorescence study in the rat

By using a double immunofluorescence method we examined the distribution of noradrenergic neurons expressing substance P receptor (NK1) or neuromedin K receptor (NK3) in the rat brainstem. The distribution of SPR-like immunoreactive (-LI) neurons completely overlapped that of tyrosine hydroxylase (TH)-LI neurons in the locus coeruleus (A6), ventrolateral and lateral reticular formation of pons (A5 and A7). Partially overlapping distribution of SPR- and TH-LI neurons were found in certain regions of the medulla oblongata (A1-A4). Neurons showing both SPR- and TH-like immunoreactivities, however, were only found in the locus coeruleus complex (A5-A7): 100% of these TH-LI neurons displayed SPR-like immunoreactivity. Neurons showing both NKR- and TH-like immunoreactivities were not detected in the aforementioned areas of brainstem. The present study has provided morphological evidence for direct physiological modulation of noradrenergic neurons by tachykinins through SPR in locus coeruleus complex (A5-A7).     

Secretin and vasoactive intestinal peptide activate tyrosine hydroxylase in sympathetic nerve endings

Secretin and vasoactive intestinal peptide (VIP) are known to stimulate tyrosine hydroxylase (TH) activity acutely in the rat superior cervical ganglion (SCG). Because TH-containing neurons in the SCG innervate the iris, submaxillary gland, and pineal gland, we examined the effects of secretin and VIP in these 3 autonomic end organs in vitro. Both peptides stimulated TH activity in each tissue. These stimulations resembled those in the SCG in that (1) secretin displayed a higher potency than VIP in all 3 end organs, (2) the peptide effects were unchanged when calcium was excluded from the incubation medium, and (3) they were mimicked by activators of the cyclic adenosine monophosphate (cAMP) pathway. These findings indicate that secretin and VIP can regulate transmitter metabolism in both the cell bodies and axon terminals of neurons originating in the SCG. Furthermore, the data raise the possibility that catecholamine synthesis in sympathetic nerve terminals is modulated by peptides released by other, nearby nerve endings.     

Development of adrenergic nerve terminals: the effects of decentralization.

The effect of decentralization (deafferentation) on the ontogeny of adrenergic nerve terminals was studied in the rat iris. Transection of the cholinergic trunk, which innervates the superior cervial ganglion (SCG), in 2–3-day-old rats, inhibited the developmental increase in iris nerve terminal density, as indicated by fluorescence microscopy. However, terminal varicosities, containing the norepinephrine (NE) storage vesicles, appeared larger and more brightly fluorescent in decentralized irides. Tyrosine hydroxylase, localized to nerve terminal cytoplasm, developed to only 40% of normal in decentralized irides. In contrast, dopamine-ß-hydroxylase, which is localized to NE storage vesicles in varicosities, developed normally. The ability to accumulate and store [³H]NE was examined in control and decentralized terminals in the presence or absence of reserpine. This drug inhibits NE storage capacity without primarily affecting accumulation itself. Decentralization reduced thein vitro uptake of NE to 54%, measured after reserpine pretreatment; in contrast,apparent uptake of transmitter was reduced to only 76% in vehicle-treated rats. These results suggest that decentralization prevents the normal development of nerve terminal membrane without markedly interfering with vesicular storage capacity. This contention was supported by the observation that in vitro retention of [³H]NE over time was actually increased in decentralized irides. Our results suggest that the ontogeny of different subcellular structures is affected differently by deafferentation.The transsynaptic regulation of nerve terminal maturation appears to be most critical in younger rats, since decentralization exerts most marked effects when performed during the perinatal period.     

Mesencephalic dopaminergic neurons expressing neuromedin K receptor (NK3): a double immunocytochemical study in the rat

By using a double immunocytochemical method we examined the distribution of dopaminergic neurons expressing neuromedin K receptor (NKR; NK₃) in the rat brain. The distribution of NKR-like immunoreactive (-LI) neurons completely overlapped that of tyrosine hydroxylase (TH)-LI neurons in the retrorubral field (A8), substantia nigra (A9), ventral tegmental area and nucleus raphe linealis (A10). Completely or partially overlapping distributions of NKR- and TH-LI neurons were found in certain regions of the hypothalamus (A11–A15) and olfactory bulb (A16). Neurons showing both NKR- and TH-like immunoreactivities, however, were only found in A8–A10: All of the NKR-LI neurons displayed TH-like immunoreactivity, and about 71–86% of the TH-LI neurons expressed NKR-like immunoreactivity. The present results provided morphological evidence for physiological modulation of dopaminergic neurons by tachykinins through NKR in A8–A10.     

The hypothalamic arcuate nucleus-median eminence complex: Immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons

In this paper, we describe the results of a series of experiments which have examined the distribution within the arcuate nucleus of the hypothalamus of neurons containing the following immunoreactivities: TH-LI, GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-LI, Leu-ENK-LI, Met-ENK-7-LI, Met-ENK-8-LI, metorphamide-LI, DYN-LI, NPY-LI, SOM-LI, FMRFamide-LI, and CLIP-LI and ependymal tanycytes containing DARPP-32-LI. Using elution-restaining and double antibody staining techniques we have established numerous patterns of coexistence of these various neurotransmitters and neuropeptides. Thus, neurons containing TH-LI were, in some instances, also found to contain GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-8-LI, Leu-ENK-LI, or DYN-LI or combinations of these compounds. For example, some TH-IR neurons also contained GAL-LI and GRF-LI, while other TH-IR neurons were also seen to contain GRF-and NT-LI. These neurons may, in fact, contain even more compounds. NPY-IR neurons and those containing SOM-LI and CLIP-LI were distinct and separate from those containing TH-LI. The distribution of these different neurochemical types of neurons and their patterns of coexistence are summarized in Fig. 34, while the relative distribution patterns of immunoreactive fibres in the median eminence are summarized in Fig. 35.     

LPS激发大鼠前脑神经元Fos和小胶质细胞OX42表达改变

目的 探讨单次腹腔注射LPS后前脑神经元和小胶质细胞的可塑性变化和相互关系。方法 应用抗Fos、抗TH或抗OX42单一、以及抗Fos／抗TH／抗OX42三重免疫组化标记方法，观察大鼠单次腹腔注射LPS后，Fos阳性神经元、Fos／TH阳性神经元、OX42阳性小胶质细胞在脑内的表达分布及时程变化，以及Fos阳性神经元或Fos／TH阳性神经元与OX42阳性小胶质细胞之间的关系。结果：Fos阳性神经元分布在额、顶皮质，扣带回和梨状皮质，外侧隔核腹侧部，杏仁中央核，海马CA2区、CA3区、齿状回，下丘脑室旁核、视上核、下丘脑外侧区和第三脑室周围灰质等。Fos阳性神经元在注射后30min出现表达，注射后1～3h为表达高峰。反应阳性小胶质细胞首先于脑室周围灰质出现，注射后6h达到高峰，胞体变大，突起变粗，OX42呈阳性深染，密集分布于Fos阳性神经元的表达区域。下丘脑Fos／TH／OX42三重染色切片显示：由LPS激活的Fos／TH阳性神经元周围被OX42阳性细胞包绕并接触，表明神经元和小胶质细胞在对LPS刺激的反应中关系密切。结论 在外周免疫刺激下，下丘脑、扣带回、梨状皮质和海马内的神经元和小胶质细胞可能参与免疫调节。     

Biological importance of retrograde axonal transport of nerve growth factor in adrenergic neurons.

Previous studies have shown that nerve growth factor (NGF) produces a selective induction of tyrosine hydroxylase (TH) in peripheral adrenergic neurons and that NGF is transported retrogradely with a high selectivity from the adrenergic nerve terminals to the perikaryon. In order to investigate the biological importance of retrograde NGF transport, the following experiments have been performed; (a) effect of NGF on TH activity in superior cervical ganglia (SCG) after unilateral injection into the anterior eye chamber and the submaxillary gland; and (b) effect of systemic injection of NGF on TH activity in SCG after blockage of retrograde axonal transport by axotomy. After unilateral injection of NGF into the anterior eye chamber and submaxillary gland of both 8-10-day-old rats and adult mice, the increase in TH activity in the SCG was considerably larger on the injected than on the non-injected side although the adrenergic neurons supplying the two organs do not account for more than 25% of the total number of adrenergic neurons in the SCG. A direct diffusion mechanism could be excluded by the fact that unilateral local injection of [125 I] produced no significant side difference in the accumulation of radioactivity in the SCG 2 after injection whereas after 14 h there was a several-fold difference between the injected and non-injected side. Moreover, the nodose ganglia which are located very close to the SCG exhibited no statistically significant difference in the accumulation of radioactivity at any time. Forty-eight hours after subcutaneous injections of 10 mg/kg of NGF the increase in TH activity of the SCG amounted to 154% on the intact side and to 92% on the axotomized side. However, these experiments do not permit decisions about the extent the axotomy, as such, impaired the response to NGF. It is concluded that the biological effect of NGF results to a considerable extent, from the moiety which reaches the cell body by retrograde transport from the nerve terminals.     

The hypothalamic arcuate nucleus-median eminence complex: immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons

In this paper, we describe the results of a series of experiments which have examined the distribution within the arcuate nucleus of the hypothalamus of neurons containing the following immunoreactivities: TH-LI, GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-LI, Leu-ENK-LI, Met-ENK-7-LI, Met-ENK-8-LI, metorphamide-LI, DYN-LI, NPY-LI, SOM-LI, FMRFamide-LI, and CLIP-LI and ependymal tanycytes containing DARPP-32-LI. Using elution-restaining and double antibody staining techniques we have established numerous patterns of coexistence of these various neurotransmitters and neuropeptides. Thus, neurons containing TH-LI were, in some instances, also found to contain GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-8-LI, Leu-ENK-LI, or DYN-LI or combinations of these compounds. For example, some TH-IR neurons also contained GAL-LI and GRF-LI, while other TH-IR. neurons were also seen to contain GRF- and NT-LI. These neurons may, in fact, contain even more compounds. NPY-IR neurons and those containing SOM-LI and CLIP-LI were distinct and separate from those containing TH-LI. The distribution of these different neurochemical types of neurons and their patterns of coexistence are summarized in Fig. 34, while the relative distribution patterns of immunoreactive fibres in the median eminence are summarized in Fig. 35.     

Retinal dopaminergic neurons (A17) expressing neuromedin K receptor (NK(3)): a double immunocytochemical study in the rat

By using a double immunofluorescence method we examined the distribution of dopaminergic neurons (A17) expressing neuromedin K receptor (NKR, NK(3)) in the rat retina. The distribution of NKR-like immunoreactive (-LI) neurons partially overlapped that of tyrosine hydroxylase (TH)-LI neurons in the inner retina of section and flat-mount preparation. Neurons showing both TH- and NKR-like immunoreactivities were found in the retina (A17): 100% of these TH-LI neurons displayed NKR-like immunoreactivity, and they constituted about 3.5% of total NKR-LI neurons. The majority of double-labeled neurons with TH- and NKR-like immunoreactivities were distributed in the proximal inner nuclear layer and the upper part of inner plexiform layer of the retina, and characterized with appearance of amacrine cells. The present study has provided morphological evidence for direct physiological modulation of dopaminergic neurons by tachykinins through NKR in the rat retina (A17).     

Overexpression of GAP-43 in thalamic projection neurons of transgenic mice does not enable them to regenerate axons through peripheral nerve grafts

It is well established that some populations of neurons of the adult rat central nervous system (CNS) will regenerate axons into a peripheral nerve implant, but others, including most thalamocortical projection neurons, will not. The ability to regenerate axons may depend on whether neurons can express growth-related genes such as GAP-43, whose expression correlates with axon growth during development and with competence to regenerate. Thalamic projection neurons which fail to regenerate into a graft also fail to upregulate GAP-43. We have tested the hypothesis that the absence of strong GAP-43 expression by the thalamic projection neurons prevents them from regenerating their axons, using transgenic mice which overexpress GAP-43. Transgene expression was mapped by in situ hybridization with a digoxigenin-labeled RNA probe and by immunohistochemistry with a monoclonal antibody against the GAP-43 protein produced by the transgene. Many CNS neurons were found to express the mRNA and protein, including neurons of the mediodorsal and ventromedial thalamic nuclei, which rarely regenerate axons into peripheral nerve grafts. Grafts were implanted into the region of these nuclei in the brains of transgenic animals. Although these neurons strongly expressed the transgene mRNA and protein and transported the protein to their axon terminals, they did not regenerate axons into the graft, suggesting that lack of GAP-43 expression is not the only factor preventing thalamocortical neurons regenerating their axons.     

Trans-synaptic regulation of the development of end organ innervation by sympathetic neurons.

To examine the regulation of development of end organ innervation the superior cervical ganglion (SCG), and two of its target organs, the iris and pineal gland, were studied using biochemical and histofluorescent approaches. During postnatal ontogeny the activity of tyrosine hydroxylase (T-OH), which is localized to adrenergic neurons, increased 50-fold in iris, and 34-fold in pineal nerve terminals of the rat. These increases paralleled the in vitro rise in iris [3H]norepinephrine ([3H]NE) uptake, a measure of the presence of functional nerve terminal membrane. These biochemical indices of end organ innervation correlated well with developmental increases in density of innervation, adrenergic ground plexus ramification and nerve fiber fluorescence intensity as determined by fluorescence microscopy. Unilateral transection of the presynaptic cholinergic nerves innervating the SCG in 2-3-day-old rats prevented the normal development of end organ innervation: T-OH activity, [3H]NE uptake, innervation density, plexus ramification and fluorescence intensity failed to develop normally in irides innervated by decentralized ganglia. It is concluded that trans-synaptic factors regulate the maturation of adrenergic nerve terminals, and the development of end organ innervation by SCG.