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R Elde

Publications and source records attributed to R Elde.

At least 37 records · Page 2Linked to original sources
PubMed1998

Immunohistochemical evidence of down-regulation of mu-opioid receptor after chronic PL-017 in rats.

In a previous study, mu-opioid receptor binding was decreased by chronic treatment of rats with a mu-opioid receptor-selective agonist [CH3Phe3, D-Pro4]morphiceptin (PL-017) [Tao, P.L., Lee, H.Y., Chang, L.R., Loh, H.H., 1990. Decrease in mu-opioid receptor binding capacity in rat brain after chronic PL-017 treatment. Brain Res. 526, 270-275]. However, there was a lack of correlation between the time course of receptor down-regulation and the loss of pharmacological effects of the drug. In the current study, we used immunohistochemistry to reinvestigate this issue. Male Sprague-Dawley rats were chronically treated with PL-017 i.c.v. for 1, 3 or 5 days, using an escalating dosage paradigm (0.75-6.0 microg), which resulted in a 1.4 to 32-fold increase in the AD50. Rat brains were removed, frozen, coronally sectioned (14 microm) and processed for mu-, delta- or kappa-opioid receptor immunohistochemistry by the avidin-biotin complex (ABC) method. Significant decreases in OP3 immunodensity were found in many brain regions which are enriched with OP3 after chronic treatment of PL-017. Time-dependent decreases in OP3 were detected and reached a plateau around 3 days of PL-017 treatment. No significant change in OP1 or OP2 immunodensity after chronic treatment with PL-017 was found. Our conclusion is that chronic treatment with PL-017 of rats selectively down-regulates mu-opioid receptors in the brain. This may be an important mechanism for PL-017 tolerance.

Animals↗
PubMed1998

Role of carboxyl terminus of mu-and delta-opioid receptor in agonist-induced down-regulation.

Chronic exposure of mu-and delta-opioid receptors to their agonists leads to different rates in receptor down-regulation. In order to analyze the role of the carboxyl terminus of mu-and delta-opioid receptors in the difference in the rate of down-regulation, two chimeras of these receptors were generated by swapping the carboxyl termini; MORTAGDT and DORTAGMT. These chimeras were tagged at the N-terminus with hemagglutinin (HA) epitope (YPYDVPDYA), which can be recognized by the monoclonal antibody 12CA5, and then stably expressed in Neuro 2A (N2A) cells. The swapping of the carboxyl termini did not alter the ligand selectivity of these receptor chimeras. However, they did exhibit a reduction in agonist potency to inhibit forskolin-stimulated adenylyl cyclase activity for all agonists tested except etorphine which had a potency comparable to that of wild type receptors. Treatment of the N2A cells expressing MORTAGDT with 50 nM etorphine produced a faster rate of receptor down-regulation when compared to the wild type mu-opioid receptor. Immunofluorescence microscopy of the MORTAGDT chimera using a monoclonal antibody against HA confirmed internalization of the receptors after treatment with etorphine for 1 and 6h. There was a reduction in the HA-immunoreactivity at the cell surface of the MORTAGDT chimera concurrent with more noticeable HA-immunoreactivity inside the cell compared to the wild type receptor. On the other hand, the rate of down-regulation of DORTAGMT receptors was seen to be the same as the wild type delta-opioid receptor after etorphine treatment. Immunofluorescence studies showed more reduction in cell surface staining of the DORTAGMT chimera compared to the wild type receptor. These data suggest the involvement of the carboxyl terminus in agonist-induced down-regulation and internalization of the nu-opioid receptor. However, different mechanisms that are unrelated to the carboxyl terminus may operate in the down-regulation of delta-opioid receptor.

Animals↗
PubMed1998

Down-regulation of mu-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy.

To understand the role of opioids and their receptors in chronic pain following peripheral nerve injury, we have studied the mu-opioid receptor in rat and monkey lumbar 4 and 5 dorsal root ganglion neurons and the superficial dorsal horn of the spinal cord under normal circumstances and after peripheral axotomy. Our results show that many small neurons in rat and monkey dorsal root ganglia, and some medium-sized and large neurons in rat dorsal root ganglia, express mu-opioid receptor-like immunoreactivity. Most of these neurons contain calcitonin gene-related peptide. The mu-opioid receptor was closely associated with the somatic plasmalemma of the dorsal root ganglion neurons. Both mu-opioid receptor-immunoreactive nerve fibers and cell bodies were observed in lamina II of the dorsal horn. The highest intensity of mu-opioid receptor-like immunoreactivity was observed in the deep part of lamina II. Most mu-opioid receptor-like immunoreactivity in the dorsal horn originated from spinal neurons. A few mu-opioid receptor-positive peripheral afferent terminals in the rat and monkey dorsal horn were calcitonin gene-related peptide-immunoreactive. In addition to pre- and post-junctional receptors in rat and monkey dorsal horn neurons, mu-opioid receptors were localized on the presynaptic membrane of some synapses of primary afferent terminals in the monkey dorsal horn. Peripheral axotomy caused a reduction in the number and intensity of mu-opioid receptor-positive neurons in the rat and monkey dorsal root ganglia, and of mu-opioid receptor-like immunoreactivity in the dorsal horn of the spinal cord. The decrease in mu-opioid receptor-like immunoreactivity was more pronounced in the monkey than in the rat dorsal root ganglia and spinal cord. It is probable that there was a parallel trans-synaptic down-regulation of mu-opioid-like immunoreactivity in local dorsal horn neurons of the monkey. These data suggest that one factor underlying the well known insensitivity of neuropathic pain to opioid analgesics could be due to a marked reduction in the number of mu-opioid receptors in the axotomized sensory neurons and in interneurons in the dorsal horn of the spinal cord.

Animals↗
PubMed1998

Immunolocalization of two mu-opioid receptor isoforms (MOR1 and MOR1B) in the rat central nervous system.

We have recently shown that the cytoplasmic tail of the rat mu-opioid receptor undergoes alternative splicing giving rise to two isoforms, rMOR1 and rMOR1B. These isoforms exhibit similar pharmacological profiles, however, differ in agonist-induced desensitization of coupling to adenylate cyclase. In the present study, we have raised polyclonal antibodies that specifically detect either rMOR1 or rMOR1B and used these antisera for immunocytochemical localization of the receptor proteins in the rat central nervous system. Prominent MOR1B-like immunoreactivity was found in the external plexiform layer of the main olfactory bulb localized to a dense plexus of dendrites mostly originating from mitral cells and extending into the glomerular layer. MOR1-like immunoreactivity was restricted to the perikarya of mitral cells and to distinct juxtaglomerular cells as well as their processes. While MOR1-, DOR1- and KOR1-like immunoreactivity was absent from the external plexiform layer, high densities of opioid peptides were found in this layer suggesting that MOR1B may be a targeted receptor of these peptides. MOR1-like immunoreactivity was observed in many pain-controlling brain areas including the spinal cord dorsal horn, sensory trigeminal complex, raphe nuclei and periaqueductal gray while MOR1B-like immunoreactivity was not detectable in these regions. Taken together, we provide evidence that the mu receptor isoforms, MOR1 and MOR1B, exhibit a strikingly different distribution in that MOR1 appears to be the major isoform widely distributed throughout the central nervous system and MOR1B being predominantly localized to the olfactory bulb.

Alternative Splicing↗
PubMed1998

Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles.

Using immunohistochemistry and immunoelectron microscopy, the localization and regulation of delta-opioid receptor-like immunoreactivity were studied in dorsal root ganglia and spinal cord of normal rat and monkey, and after peripheral axotomy. Delta-opioid receptor-like immunoreactivity was observed in many small dorsal root ganglion neurons, and in the rat most of them contained substance P and calcitonin gene-related peptide. At the ultrastructural level, delta-opioid receptor-like immunoreactivity was localized in the Golgi complex, on the membrane of the large dense-core vesicles and on the membrane of and/or inside a type of large vesicle with an interior of low electron density. The latter vesicles were often in contact with multivesicular bodies. In the superficial dorsal horn of the spinal cord, most delta-opioid receptor-positive nerve fibers contain substance P and/or calcitonin gene-related peptide, both in rat and monkey. Also, in these nerve endings delta-opioid receptor-like immunoreactivity was found on the membrane of large dense-core vesicles and on the membrane of, or in, the lucent vesicles. Occasionally, delta-opioid receptor-like immunoreactivity was observed on the plasmalemma of the terminals, particularly when the vesicles were in exocytotic contact with the plasmalemma. Peripheral axotomy induced a decrease in delta-opioid receptor-like immunoreactivity both in cell bodies in the dorsal root ganglia and in terminals in the dorsal horn. These data suggest that the delta-opioid receptor may be a constituent of the membrane of large dense-core vesicles storing and releasing neuropeptides. It is suggested that upon exocytotic release of substance P and calcitonin gene-related peptide from large dense-core vesicles, there is a transient modification of the surface of the primary afferent terminals which leads to exposure of the receptor protein so that enkephalin released from adjacent terminals can activate the receptor. The decrease in delta-opioid receptors after axotomy indicates that delta-opioid receptor-mediated inhibitory effects are attenuated at the spinal level both in the rat and monkey.

Animals↗
PubMed1998

Effects of neurotoxins and hindpaw inflammation on opioid receptor immunoreactivities in dorsal root ganglia.

Three types of opioid receptors mediate peripheral opioid antinociception in inflammation. Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid receptors have been developed. Using these antisera we examined the regulation of opioid receptors in rat dorsal root ganglia after hindpaw inflammation and the influence of neurotoxins for primary afferent neurons and sympathetic neurons thereon. Peripheral tissue inflammation was produced by injection of complete Freund's adjuvant into the right hindpaw. Capsaicin was injected subcutaneously once a day for three days using a total dose of 150 mg/kg. 6-hydroxydopamine was injected intraperitoneally 75 mg/kg/day for three days. Freund's adjuvant induced a marked increase in the percentage of mu-, but a decrease in delta- and kappa-opioid receptor-positive neurons. Capsaicin significantly decreased mu-, delta- and kappa-opioid receptor immunoreactivity in both Freund's adjuvant treated and non-treated rats. No significant changes on the mu-, delta- and kappa-opioid receptor immunoreactivities were observed after 6-hydroxydopamine treatment in either Freund's adjuvant-treated or non-treated rats. Our studies indicate: (1) Peripheral inflammation can differentially regulate the expression of the three opioid receptors in dorsal root ganglia neurons with an up-regulation of mu- and down-regulation of delta- and kappa-opioid receptors. 2) A significant portion of mu-, delta- and kappa-opioid receptors are located on capsaicin-sensitive neurons in dorsal root ganglia of both non-inflamed and inflamed hindlimbs. 3) The expression of opioid receptors in dorsal root ganglia of either inflamed or non-inflamed hindlimbs is not influenced by sympathetic postganglionic neurons.

Animals↗
PubMed1998

P2X3 is expressed by DRG neurons that terminate in inner lamina II.

The P2X3 receptor subunit, a member of the P2X family of ATP-gated ion channels, is almost exclusively localized in sensory neurons. In the present study, we sought to gain insight into the role of P2X3 and P2X3-containing neurons in sensory transmission, using immunohistochemical approaches. In rat dorsal root ganglia (DRG), P2X3-immunoreactivity (-ir) was observed in small- and medium-sized neurons. Approximately 40% of DRG neuronal profiles in normal rats contained P2X3-ir. In rats that had received neonatal capsaicin treatment, the number of P2X3-positive neurons was decreased by approximately 70%. Analysis of the colocalization of P2X3-ir with cytochemical markers of DRG neurons indicated that approximately 94% of the P2X3-positive neuronal profiles were labelled by isolectin B4 from Bandeiraea simplicifolia, while only 3% contained substance P-ir, and 7% contained somatostatin-ir. In dorsal horn of rat spinal cord, P2X3-ir was observed in the inner portion of lamina II and was reduced subsequent to dorsal rhizotomy, as well as subsequent to neonatal capsaicin treatment. Finally, P2X3-ir accumulated proximal to the site of sciatic nerve ligation, and was seen in nerve fibres in skin and corneal epithelium. In summary, our results suggest that P2X3 is expressed by a functionally heterogeneous population of BSI-B4-binding sensory neurons, and is transported into both central and peripheral processes of these neurons.

Animals↗
PubMed1997

Distinct ATP receptors on pain-sensing and stretch-sensing neurons.

The initial pain from tissue damage may result from the release of cytoplasmic components that act upon nociceptors, the sensors for pain. ATP was proposed to fill this role because it elicits pain when applied intradermally and may be the active compound in cytoplasmic fractions that cause pain. Moreover, ATP opens ligand-gated ion channels (P2X receptors) in sensory neurons and only sensory neurons express messenger RNA for the P2X3 receptor. To test whether ATP contributes to nociception, we developed a tissue culture system that allows comparison of nociceptive (tooth-pulp afferent) and non-nociceptive (muscle-stretch receptor) rat sensory neurons. Low concentrations of ATP evoked action potentials and large inward currents in both types of neuron. Nociceptors had currents that were similar to those of heterologously expressed channels containing P2X3 subunits, and had P2X3 immunoreactivity in their sensory endings and cell bodies. Stretch receptors had currents that differed from those of P2X3 channels, and had no P2X3 immunoreactivity. These results support the theory that P2X3 receptors mediate a form of nociception, but also suggest non-nociceptive roles for ATP in sensory neurons.

Action Potentials↗
PubMed1997

Vesicular acetylcholine transporter (VAChT) protein: a novel and unique marker for cholinergic neurons in the central and peripheral nervous systems.

Acetylcholine (ACh) is synthesized in nerve terminals from choline and acetyl coenzyme A by the cytoplasmic enzyme choline acetyltransferase (ChAT). The neurotransmitter is thereafter transported into synaptic vesicles, where it is stored until release. cDNA clones encoding a vesicular ACh transporter (VAChT) were recently isolated. In this paper, we report on the generation of highly specific goat polyclonal antisera to the rat VAChT protein by using a synthetic carboxy-terminal 20-amino-acid peptide sequence as an immunogen. Characterization of the antisera revealed recognition of VAChT, but not vesicular monoamine transporter (VMAT) protein, in transfected CV-1 cells. VAChT immunoreactivity was also detected in cells that endogenously express the protein, such as in PC12 cells and in primary cultures of spinal motoneurons. Absorption controls showed that the VAChT antisera could be completely blocked at the 10(-5) M concentration by cognate peptide used for immunization. The antisera cross-reacted with the VAChT protein in rat and mouse but not in guinea pig, rabbit, or cat. Immunohistochemistry and confocal laser microscopy, using the goat VAChT antisera, showed strong immunoreactivity in discrete fibers and neuronal cell bodies of the central and peripheral nervous systems. Within cell bodies and axonal nerve terminals, as well as in dendrites, the staining appeared granular, presumably representing labeling of synaptic vesicles containing ACh. In the rat central nervous system, VAChT-positive cell bodies were demonstrated in the cerebral cortex, striatum, septum, nucleus basalis, medial habenula, mesopontine complex, cranial, and autonomic and spinal motor nuclei and in the intermediomedial region near the central canal. High densities of VAChT-immunoreactive axonal fibers were encountered in areas such as the olfactory bulb, cerebral cortex, striatum, basal forebrain, amygdala, thalamus, hypothalamus including median eminence, hippocampal formation, superior colliculus, interpeduncular nucleus, and pedunculopontine and laterodorsal tegmental nuclei. In cranial and spinal motor nuclei, particularly large varicosities were seen in close proximity to the motoneuron cell somata and their proximal dendrites. In the peripheral nervous system, VAChT immunoreactivity was also detected in motor endplates of skeletal muscle as well as in fibers of sympathetic and parasympathetic abdominal ganglia, heart atrium, respiratory tract, gastrointestinal tract, pancreas, adrenal medulla, male genitourinary tract, and salivary and lacrimal glands. Direct double labeling revealed colocalization of VAChT and ChAT immunoreactivity in neurons. The results show that VAChT antisera represent novel and unique tools for the study of cholinergic neurons in the central and peripheral nervous systems.

Animals↗
PubMed1997

Immunocytochemical localization of mu-opioid receptors in follicular cells and preimplantation mouse embryos.

It has been demonstrated that opioid peptides are involved in the regulation of mammalian reproduction. In our previous studies we demonstrated direct effects of opioids on preimplantation mouse embryos, and hypothesized the existence in preimplantation embryos of receptors similar to opioid receptors in the central neuronal system of adult animals. In the present study we addressed this issue by employing immunocytochemical staining for mu-opioid receptors using antisera raised against the C-terminal portion of the cloned mu-opioid receptors (MOR1, NHQLENLEAETAPLP, 384-398) predicted from the cloned receptor. Diffuse MOR1 immunoreactivity of moderate intensity has been revealed in one-cell embryos, while in follicular cells MOR1 staining was of high intensity and appeared to be associated with plasma membrane. No MOR1 immunoreactivity has been observed in two-cell to morula stages of development. However, blastocysts displayed intense MOR1-labeling that was particularly prominent in cells within the inner cell mass. MOR1-staining was most likely specific because preincubation of MOR1 antisera with cognate peptide completely abolished the staining. Our findings suggest the presence of opioid receptors during preimplantation development, long before the formation of the nervous system. Embryonic opioid receptors may play a role in the regulation of preimplantation development and implantation.

Animals↗
PubMed1997

Immunohistochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals.

Of the cloned P2X receptor subunits, six are expressed in sensory neurons, suggesting that the native channels may be heteromultimers with diverse composition. It has been proposed that P2X2 and P2X3 form heteromultimers in sensory neurons. We further tested this hypothesis by examining the relationship of P2X2 and P2X3 immunocytochemically. In rat dorsal root and nodose ganglia, P2X2- and P2X3-immunoreactivity (-ir) were highly colocalized, although single-labeled cells were also present. In dorsal root ganglia (DRG), in some cases P2X2-ir appeared to be present in satellite cells. In dorsal horn of spinal cord, at low magnification the laminar localization of P2X2- and P2X3-ir overlapped, but at high magnification colocalization was rarely observed. In contrast, in the solitary tract and its nucleus (NTS), colocalization of P2X2- and P2X3-ir was seen at low and high magnification. These results suggest that the relationship of P2X2- and P2X3-ir is different in nodose and dorsal root ganglia and might reflect differences in the targeting of P2X receptors in different sensory neurons. In monkey, P2X2-ir was observed in DRG neurons and satellite cells and in dorsal horn of spinal cord. P2X3-ir was also seen in DRG neurons. However, the presence of P2X2-ir in NTS as well as the presence of P2X3-ir in spinal cord and NTS could not be established definitively. These results suggest species differences, although a more extensive study of primate sensory systems is necessary.

Animals↗
PubMed1997

mu-opioid receptor regulates CFTR coexpressed in Xenopus oocytes in a cAMP independent manner.

The objective of this study was to characterize the signaling mechanisms of the mu-opioid receptor in its coupling to the cystic fibrosis transmembrane conductance regulator (CFTR) when coexpressed in Xenopus oocytes. Because oocytes do not contain endogenous cAMP-regulated ion channels, the cAMP-modulated CFTR was coexpressed with receptors as a 'reporter' channel. Agonist treatment of oocytes coexpressing mu-opioid receptors, beta2-adrenergic receptors and CFTR produced Cl- currents in a dose-related manner and immunocytochemical analysis confirmed receptor expression. These data suggest that opioid agonists could activate adenylyl cyclase in this system to elevate cAMP levels. Heterotrimeric G protein betagamma-subunits acting on adenylyl cyclase type II would increase cAMP levels. The probable presence of adenylyl cyclase type II and other components of opioid signal transduction such as G(i alpha2), were demonstrated by RT-PCR. However, measurement of cAMP levels in individual oocytes by radioimmunoassay showed that opioid agonist application to oocytes expressing mu-opioid receptors, beta2-adrenergic receptors and CFTR did not increase cAMP levels, whereas application of the beta2-adrenergic agonist, isoproterenol, or IBMX alone did increase cAMP levels. Opioid-induced CFTR activation was not affected by either application of the broad spectrum kinase inhibitor, H7, nor by application of the specific PKA inhibitor, KT5720. Injection of free betagamma-subunits, which could activate the endogenous type II cyclase, was unable to produce measurable currents in oocytes expressing the CFTR. These studies indicate that opioid activation of the CFTR is not mediated through a cAMP/PKA pathway, by either betagamma-subunit activation of an adenylyl cyclase type II or promiscuous coupling to G(s alpha).

Amino Acid Sequence↗
PubMed1996

Immunofluorescence analysis of antisense oligodeoxynucleotide-mediated 'knock-down' of the mouse delta opioid receptor in vitro and in vivo.

We have previously used antisense oligodeoxynucleotides (ODN) to the cloned delta opioid receptor (DOR) to inhibit the antinociceptive response to spinally administered delta opioid receptor selective agonists in mice. Here we have examined the effect of DOR antisense ODN treatment on the level of DOR expressed in NG 108-15 cells and the spinal cord, through immuno-fluorescence microscopy, to determine the efficiency and selectivity of the antisense ODN-mediated "knock-down' of the DOR in these tissues. Antisense ODN, but not mismatch control, treatment resulted in a significant reduction in DOR immunoreactivity (-ir) in NG 108-15 cells and spinal cord. Thus, the inhibition of antinociceptive response to intrathecal delta selective agonists by DOR antisense ODN correlates with the loss of DOR-ir in the superficial layers of the dorsal horn of the spinal cord.

Animals↗
PubMed1996

Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry.

Several P2X receptor subunits were recently cloned; of these, one was cloned from the rat vas deferens (P2X1) and another from pheochromocytoma (PC12) cells differentiated with nerve growth factor (P2X2). Peptides corresponding to the C-terminal portions of the predicted receptor proteins (P2X1 391-399 and P2X2 460-472) were used to generate antisera in rabbits. The specificities of antisera were determined by staining human embryonic kidney cells stably transfected with either P2X1 or P2X2 receptors and by absorption controls with the cognate peptides. In the vas deferens and the ileal submucosa, P2X1 immunoreactivity (ir) was restricted to smooth muscle, whereas P2X2-ir was restricted to neurons and their processes. Chromaffin cells of the adrenal medulla and PC12 cells contained both P2X1- and P2X2-ir. P2X1-ir was also found in smooth muscle cells of the bladder, cardiac myocytes, and nerve fibers and terminals in the superficial dorsal horn of the spinal cord. In contrast, P2X2-ir was observed in scattered cells of the anterior pituitary, neurons in the hypothalamic arcuate and paraventricular nuclei, and catecholaminergic neurons in the olfactory bulb, the substantia nigra, ventral tegmental area, and locus coeruleus. A plexus of nerve fibers and terminals in the nucleus of the solitary tract contained P2X2-ir. This staining disappeared after nodose ganglionectomy, consistent with a presynaptic function. The location of the P2X1 subunit in smooth muscle is consistent with its role as a postjunctional receptor in autonomic transmission, while in neurons, these receptors appear in both postsynaptic and presynaptic locations.

Amino Acid Sequence↗
PubMed1996

Orphanin FQ/nociceptin-immunoreactive nerve fibers parallel those containing endogenous opioids in rat spinal cord.

Antisera were developed that specifically recognize orphanin FQ/nociceptin, the 17 amino acid peptide reported to be the endogenous ligand for the orphan opioid receptor. Immunocytochemical localizations in rat spinal cord demonstrated that orphanin FQ /nociceptin-immunoreactivity (-ir) was abundant in superficial dorsal horn, lateral spinal nucleus and the region dorsal to the central canal, areas that also exhibit prominent enkephalin-and dynorphin-ir. Orphanin FQ/nociceptin-ir was not affected by dorsal rhizotomy, indicating that in spinal cord the peptide is produced by central rather than primary afferent neurons. thus, the distribution of orphanin FQ/nociceptin-ir appeared in neuronal circuits that parallel those containing enkephalin- and dynorphin-ir, with only modest co-existence of these peptides.

Amino Acid Sequence↗
PubMed1996

Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1).

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat which encodes glutamine in the novel protein ataxin-1. In order to characterize the developmental expression pattern of SCA1 and to identify putative functional domains in ataxin-1, the murine homolog (Sca1) was isolated. Cloning and characterization of the murine Sca1 gene revealed that the gene organization is similar to that of the human gene. The murine and human ataxin-1 are highly homologous but the CAG repeat is virtually absent in the mouse sequence suggesting that the polyglutamine stretch is not essential for the normal function of ataxin-1 in mice. Cellular and developmental expression of the murine homolog was examined using RNA in situ hybridization. During cerebellar development, there is a transient burst of Sca1 expression at postnatal day 14 when the murine cerebellar cortex becomes physiologically functional. There is also marked expression of Sca1 in mesenchymal cells of the intervertebral discs during development of the spinal column. These results suggest that the normal Sca1 gene, has a role at specific stages of both cerebellar and vertebral column development.

Amino Acid Sequence↗
PubMed1995

Effect of vibrissae deprivation on follicle innervation, neuropeptide synthesis in the trigeminal ganglion, and S1 barrel cortex plasticity.

Deprivation of vibrissae from an early age causes plasticity in S1 barrel cortex. This method of deprivation is most likely to induce plasticity by altering the balance of primary afferent activity from the deprived and spared vibrissae. To study whether or not induction or expression of this type of plasticity might be affected by follicle nerve injury caused by the deprivation technique, three different methods of detecting nerve injury were used: counting axon numbers in the distal follicle nerve, quantifying morphological changes in axons, and measuring neuropeptide expression in the trigeminal ganglion cells. First, nerves innervating follicles chronically deprived of vibrissae from birth had the same number of myelinated and unmyelinated axons as nerves from normally reared animals. Second, axons innervating deprived follicles showed no morphological changes in myelination or mitochondria characteristic of damaged nerves. Third, the corresponding nerve cell bodies in the trigeminal ganglion did not show upregulation of galanin or neuropeptide Y expression. In contrast, animals receiving mild injury of the follicle nerve endings (by cauterization of the follicle) showed profound changes in axonal myelination and mitochondria and increases in neuropeptide expression. These results imply that vibrissae deprivation does not act by inducing injury of the follicular nerve, suggesting that changes in the balance of follicle nerve activity are the cause of cortical plasticity. Consistent with this notion, a fourth experiment demonstrated that trimming the vibrissae induces cortical plasticity comparable to that induced by complete vibrissae removal.

Afferent Pathways↗