Biomedical subjects

T Hökfelt

Publications and source records attributed to T Hökfelt.

At least 19 recordsLinked to original sources

PubMed1996

Specific induction of protein kinase C delta subspecies after transient middle cerebral artery occlusion in the rat brain: inhibition by MK-801.

Protein kinase C (PKC) consists of a family of closely related Ca2+/phospholipid-dependent phosphotransferase isozymes, most of which are present in the brain and are differentially activated by second messengers. Calcium-dependent PKC activity may cause neuronal degeneration after ischemic insult. PKC is also involved in trophic-factor signaling, indicating that activity of some PKC subspecies may be beneficial to the injured brain. Therefore, we screened long-term changes in the expression of multiple PKC subspecies after focal brain ischemia. Middle cerebral artery occlusion was produced by using an intraluminal suture for 30 min of 90 min. In in situ hybridization experiments, mRNA levels of PKC alpha, -beta, -gamma, -delta, -epsilon, and -zeta were decreased in the infarct core 4 hr after ischemia and were lost completely 12 hr after ischemia. In areas surrounding the core, PKC delta mRNA was specifically induced 4, 12, and 24 hr after ischemia in the cortex. At 3 and 7 d, the core and a rim around it showed increased mRNA levels of PKC delta. No other subspecies were induced. At 2 d, immunoblotting demonstrated increased levels of PKC delta protein in the perifocal tissue, and immunocytochemistry revealed an increased number of PKC delta-positive neurons in the perifocal cortex. In the core, PKC delta-positive macrophages and endothelial cells were seen. Pretreatment with MK-801, an NMDA antagonist, inhibited cortical PKC delta mRNA induction. The data show that focal brain ischemia induces PKC delta mRNA and protein but not other PKC subspecies through the activation of NMDA receptors and that the upregulation lasts for several days in neurons of the perifocal zone.

Animals↗

PubMed1996

Phenotype of intraadrenal ganglion neurons during postnatal development in rat.

The postnatal development of intraadrenal ganglion neurons was studied in rat by using indirect immunohistochemistry and in situ hybridization. The large neuropeptide tyrosine (NPY)-expressing ganglion neurons (type I ganglion neurons) matured postnatally, with marked increases in acetylcholinesterase (AChE)-, neurofilament 10 (NF10)-, and tyrosine hydroxylase (TH)-like immunoreactivities (LIs) paralleled by increasing levels of mRNAs encoding NPY, low-affinity neurotrophin receptor (LANR), and tropomyosin kinase receptor (trk). The smaller vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) ganglion neurons (type II ganglion neurons) expressed increasing levels of VIP mRNA postnatally and also contained immunoreactive nitric oxide synthase (NOS) and its mRNA. These type II ganglion neurons appeared to be relatively mature already at postnatal day (P2) and did not express detectable levels of LANR or trk mRNAs. The cell size of both the type I and type II ganglion neurons increased about 2.5-fold postnatally. The type I ganglion neurons formed more densely packed clusters with increasing age, whereas the type II ganglion neurons were spread out in small groups or individually, mainly in the peripheral parts of the medulla, and appeared to fulfill their migration into the medulla and/or to the inner regions of the cortex early postnatally, possibly after establishing contact with their cortical targets. We suggest that the type I ganglion neurons represent sympathetic ganglion neurons of the same origin as the chromaffin cells and that they mature mainly postnatally. The development of the type II (VIP/NOS) ganglion neurons takes place earlier; however, their phenotype remains more uncertain.

Acetylcholinesterase↗

PubMed1996

Ca2+/calmodulin-dependent protein kinase type IV in dorsal root ganglion: colocalization with peptides, axonal transport and effect of axotomy.

Using the indirect immunofluorescence technique, the distribution of Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) was studied in dorsal root ganglia (DRGs) and the sciatic nerve under normal circumstances and after axotomy and nerve ligation. CaM kinase IV-like immunoreactivity (-LI) was observed mainly in small DRG neurons but also in some large ones with the immunoreactivity mainly confined to the cell nuclei and with varying levels in the cytoplasm. CaM kinase IV-LI was present in around 1/4 of all CGRP-positive neurons and in the vast majority of the somatostatin-positive neurons. The enzyme levels decreased markedly after axotomy. The enzyme was also observed in axons in the sciatic nerve and accumulated both proximal and distal to a ligation. The present results suggest that CaM kinase is not of direct importance for upregulation of neuropeptides in DRG neurons after nerve injury. In addition to a nuclear function it may also play a role in the peripheral processes of DRG neurons.

Animals↗

PubMed1996

Vanilloid receptor loss is independent of the messenger plasticity that follows systemic resiniferatoxin administration.

Resiniferatoxin (RTX) depletes vanilloid (capsaicin) receptors from lumbar dorsal root ganglia (DRG) of the rat. In addition, RTX causes changes in neuropeptide and nitric oxide synthase expression in lumbar DRG neurons, similar to those described following axotomy; this latter phenomenon is referred to as messenger plasticity. These findings suggested that vanilloid receptor loss may be part of the plasticity that follows RTX treatment. Here we show that vanilloid receptor expression, as detected by [3H]RTX autoradiography, is not changed in lumbar DRGs of axotomized rats, nor is it altered in a rat model (chronic constriction injury) of neuropathic pain. Thus, the in vivo expression of vanilloid receptors detected by specific [3H]RTX binding does not require the presence of intraaxonally transported trophic factors such as nerve growth factor. We conclude that messenger plasticity and vanilloid receptor loss are mediated by distinct mechanisms.

Animals↗

PubMed1996

GDNF mRNA in Schwann cells and DRG satellite cells after chronic sciatic nerve injury.

Glial cell line-derived neurotrophic factor (GDNF) exhibits neurotrophic properties on different types of neurones, including fetal motoneurones and embryonic neurones of sensory ganglia. We demonstrate that chronic injury to the adult rat sciatic nerve induces a rapid up-regulation of GDNF mRNA expression in Schwann cells proximal as well as distal to the injury site, and that expression of this mRNA remains at high levels for at least 5 months after injury. In addition, GDNF mRNA increases and remains high in satellite cells and Schwann cells of the affected L4/L5 DRGs. These findings suggest that GDNF is an important factor in the events that follow upon adult chronic primary sensory neurone injury, and possibly also after adult motoneurone axotomy.

Animals↗

PubMed1996

The distribution and significance of CNS adrenoceptors examined with in situ hybridization.

Several of the established alpha 1-, alpha 2- and beta-adrenoceptors have now been isolated and cloned. The in situ hybridization method has been used to map the distribution of many of these adrenoceptors within cells of the CNS. These studies add complementary and new information to our knowledge of adrenoceptor localization provided previously by radioligand-mediated autoradiography. Neuronal cell groups containing one or more mRNAs for seven adrenoceptor subtypes throughout the rat CNS have been mapped. In the present review Anthony Nicholas, Tomas Hökfelt and Vincent Pieribone will examine these localizations and discuss the additional information these maps supply, as well as some implications for understanding central noradrenaline and adrenaline systems.

Animals↗

PubMed1996

Immunohistochemical mapping of nitric oxide synthase in the rat hypothalamus and colocalization with neuropeptides.

The localization and distribution of nitric oxide synthase in the hypothalamus have been studied with an immunohistochemical technique using antibodies to neuronal rat nitric oxide synthase. Subsequent double-labeling experiments examined the colocalization patterns of nitric oxide synthase and several peptides. Our results demonstrate a widespread occurrence of nitric oxide synthase-immunoreactive nerve cell bodies and processes throughout the hypothalamus, especially in various parts of the preoptic region, in the supraoptic and paraventricular nuclei, the lateral hypothalamic area, the ventromedial and dorsomedial nuclei, the arcuate nucleus and various parts of the mammillary region. Double labeling experiments showed that nitric oxide synthase-like immunoreactivity coexists with substance P-like immunoreactivity in the medial preoptic area, with oxytocin-, cholecystokinin-and galanin message-associated peptide-like immunoreactivity in the supraoptic nucleus, with enkephalin, oxytocin- and corticotropin releasing factor-like immunoreactivity in the paraventricular nucleus and with enkephalin-like immunoreactivity in the arcuate nucleus. Furthermore, in the ventromedial nucleus, nitric oxide synthase-like immunoreactivity coexisted with enkephalin-, substance P-, and somatostatin-like immunoreactivity, and in the dorsomedial nucleus with enkephalin-, galanin message-associated peptide-and substance P-like immunoreactivity. In the mammillary region nitric oxide synthase-like immunoreactivity coexisted with enkephalin-, cholecystokinin-, and substance P-like immunoreactivity. Among these neuropeptides, enkephalin and substance P were most frequently found in nitric oxide synthase-immunoreactive neurons. We conclude that nitric oxide synthase-immunoreactive neurons contain neuropeptides in various parts of the hypothalamus, and that nitric oxide in the hypothalamus may be involved in a variety of neuroendocrine and autonomic functions.

Animals↗

PubMed1996

Expression of Fos-related antigens, oxytocin, dynorphin and galanin in the paraventricular and supraoptic nuclei of lactating rats.

The magnocellular oxytocin neurons within the paraventricular and supraoptic nuclei (PVN and SON) of the hypothalamus are important relays in the milk ejection reflex in lactating animals, and are activated by suckling. It has been suggested that proto-oncogene transcription factors such as Fos/Jun act as early nuclear transducers of sensory stimuli in neurons. Therefore, we have studied with immunohistochemistry Fos-related antigens (FRAs) as a marker for neuronal activity in the PVN and SON during suckling in lactating rats. In nonlactating rats, only few cells exhibiting FRAs were observed in these nuclei. Also in lactating rats subjected to continuous suckling Fos-like activity was low. In contrast, lactating rats separated from their pups for 4 h and then exposed to suckling for 1 h expressed strong Fos-like immunoreactivity, both in vasopressin and oxytocin neurons. Using in situ hybridization and immunohistochemistry we have also investigated the expression of the mRNAs for oxytocin, dynorphin, galanin and galanin message-associated peptide and of oxytocin and dynorphin in the PVN of lactating and nonlactating rats. In lactating rats, an increase in oxytocin and dynorphin and their mRNAs was observed, whereas mRNAs for galanin and galanin message-associated peptide were downregulated. With the help of immunohistochemistry and double-staining methods, a substantial coexistence between oxytocin- and dynorphin-like immunoreactivities was shown in magnocellular neurons. These results indicate that FRAs are activated in the PVN in the beginning of a suckling period, while this response cannot be seen after continuous stimulation. Furthermore, in the PVN of lactating rats, an upregulation of oxytocin and dynorphin occurs while galanin expression decreases. Finally, the coexistence between oxytocin and dynorphin is more pronounced in lactating rats and nonlactating female rats than has previously been described in male rats.

Animals↗

PubMed1995

Expression of pituitary adenylate cyclase-activating polypeptide in dorsal root ganglia following axotomy: time course and coexistence.

Pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been demonstrated in sensory neurons. In the present study on rat 17.5% of all neurons, mainly of small size, contained PACAP in normal dorsal root ganglia (DRGs). Transection of the sciatic nerve induced a rapid and strong upregulation in PACAP peptide and mRNA levels which could be seen already after 15 h. After 3 days more than 51.5% of neurons of different sizes expressed PACAP. However, the intensity of PACAP-LI in the DRG neurons declined after 10 days. Thirty days after axotomy, 56.7% of the DRG neurons still expressed PACAP, but with a low intensity, in fact even lower than in normal controls. No VIP- or NPY-positive neurons were observed in normal or axotomized DRGs at 15 h. However a distinct increase in VIP and NPY levels were seen 3 days after the lesion, and their levels were considerably higher after 30 days. PACAP was often present in neurons expressing VIP, NPY and/or galanin. Thus, 3 days after injury, PACAP was present in 84.4%, 95.7%, and 76.8% of the VIP-, NPY-, and galanin-positive neurons, respectively. PACAP was also found in nerve fibers in control sciatic nerves. After nerve ligation, accumulation of PACAP was seen mainly proximal to the injury but also distally, suggesting both anterograde and retrograde transport of the peptide. Also a moderate increase (about 20%) in PACAP levels was found in the superficial spinal dorsal horn 3 days after nerve transection. Taken together, our results suggest that PACAP is involved in the response to nerve injury. The very high levels of expression in different populations of DRG neurons after axotomy, and its different time course as compared to galanin, NPY and VIP indicate that it may play a complementary and/or different role than these peptides in the adaptation to nerve injury, especially in its early phase.

Animals↗

PubMed1995

The cholinergic innervation of the adrenal gland and its relation to enkephalin and nitric oxide synthase.

Using a monoclonal antibody against rat brain choline acetyltransferase (ChAT) the cholinergic innervation of the adult rat adrenal gland was visualized. Almost all ChAT-positive fibres contained nitric oxide synthase (NOS), whereas enkephalin (ENK) was exclusively found in ChAT fibres among adrenaline chromaffin cells. The ChAT/NOS/ENK fibres disappeared after immunological sympathectomy, indicating a preganglionic origin. ChAT was not found in the superficial peptide- and NOS containing fibre plexus in the adrenal cortex or in small or large intra-adrenal ganglion neurones under control conditions. Even after colchicine treatment only one single ChAT-positive small ganglion neurone was found. It is possible, therefore that some small intra-adrenal ganglion neurones, which express NOS- and VIP-like immunoreactivities, are noncholinergic, nonadrenergic neurones.

Adrenal Glands↗

PubMed1995

Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment.

Vanilloid (capsaicin) receptors were visualized by [3H]resiniferatoxin (RTX) autoradiography in the brain of newborn as well as adult (both control and colchicine-treated) rats. Specific labelling was seen in the brain stem only, in the nucleus of the solitary tract extending into the area postrema and the spinal sensory nucleus of the trigeminal nerve. Also, a strong signal was seen in the dorsal horn, dorsal root, trigeminal and nodose ganglia. Membranes obtained from the cervical, thoracic, and lumbar segments of the spinal cord showed similar affinities for RTX and likewise for capsaicin and capsazepine; maximal receptor density was similar in the cervical and thoracic segments (approximately 70 fmol/mg protein) but was twice as high in the lumbar segment. 24 h after ligation of the vagal or the sciatic nerves, a strong accumulation of specific RTX binding sites was observed mainly proximal to the ligature, implying intraaxonal receptor transport from the nodose and dorsal root ganglia, respectively, to the periphery. Systemic (s.c.) vanilloid treatment depleted specific [3H]RTX binding sites from the brain stem, the sensory (dorsal root as well as trigeminal) ganglia, and the spinal cord. RTX was approximately 200-fold more potent than capsaicin for eliminating vanilloid receptors from the spinal cord. The present results suggest a discrete expression of vanilloid receptors in the brain stem (sensory nuclei); although intrinsic vanilloid receptor-expressing neurons are though to exist in the rat brain, they remain undetected by the present [3H]RTX autoradiography methodology.

Animals↗

PubMed1995

Localization of choline acetyltransferase in rat peripheral sympathetic neurons and its coexistence with nitric oxide synthase and neuropeptides.

Indirect immunofluorescence methods using a mouse monoclonal antibody raised to rat choline acetyltransferase (ChAT) revealed dense networks of ChAT-immunoreactive fibers in the superior cervical ganglion, the stellate ganglion, and the celiac superior mesenteric ganglion of the rat. Numerous and single ChAT-immunoreactive cell bodies were observed in the stellate and superior cervical ganglia, respectively. The majority of ChAT-immunoreactive fibers in the stellate and superior cervical ganglia were nitric oxide synthase (NOS) positive. Some ChAT-immunoreactive fibers contained enkephalin-like immunoreactivity. Virtually all ChAT-positive cell bodies in the stellate ganglion were vasoactive intestinal polypeptide (VIP)-positive, and some were calcitonin gene-related peptide (CGRP)-positive. After transection of the cervical sympathetic trunk almost all ChAT- and NOS-positive fibers and most enkephalin- and CGRP-positive fibers disappeared in the superior cervical ganglion. The results suggest that most preganglionic fibers are cholinergic and that the majority of these in addition can release nitric oxide, some enkephalin, and a few CGRP. Acetylcholine, VIP, and CGRP are coexisting messenger molecules in some postganglionic sympathetic neurons.

Animals↗

PubMed1995

Effects of aging on the expression of neurotrophins and their receptors in the rat pituitary gland.

We studied the effect of aging on the mRNA levels of neurotrophins and their receptors in the rat pituitary gland using in situ hybridization. In 2-month-old rats, mRNA for brain derived neurotrophic factor (BDNF) was observed in the anterior and intermediate lobes of the pituitary. TrkB and trkC, the putative receptors for BDNF and neurotrophin-3, were also expressed in the pituitary. In contrast, trk mRNA could not be detected in any of the pituitaries studied. Aging did not affect BDNF mRNA levels. In 2-year-old rats, trkB and trkC mRNA levels were decreased in the anterior lobe. TrkB mRNA levels decreased also in the neural lobe. These results show that although the expression of BDNF does not change during aging in the pituitary, expression of trkB and trkC mRNAs are altered in senescence. These changes may reflect overall impairments in pituitary endocrine functions in old age or they may be associated with morphological alterations in pituitary innervation.

Aging↗

PubMed1995

Increased levels of GMAP, VIP and nitric oxide synthase, and their mRNAs, in lumbar dorsal root ganglia of the rat following systemic resiniferatoxin treatment.

Using in situ hybridization, the expression of mRNA encoding galanin, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and nitric oxide synthase (NOS), respectively, was studied in lumbar dorsal root ganglia of rats given a single s.c. dose of 300 micrograms kg-1 resiniferatoxin (RTX), an ultrapotent capsaicin analogue. In control animals, 10% of the DRG neurones were positive for galanin mRNA, whereas no message for VIP, NPY or NOS could be detected. One week after RTX treatment, a markedly increased number (approximately 30%) of the neurones expressed galanin mRNA. Simultaneously, VIP and NOS mRNA became detectable in 6-8% of the neurones. The number of galanin-positive neurones declined after 2 weeks and returned to control levels by 8 weeks. The increase in number of VIP-, or NOS-positive neurones persisted up to 4 weeks after RTX treatment and declined thereafter. Also, there was a small increase in NPY mRNA-positive neurones. In parallel immunohistochemical experiments, similar increases were observed for galanin message-associated protein (GMAP)-, VIP- and NOS-like immunoreactivities. Our findings suggest that RTX can cause changes (messenger plasticity) in galanin, VIP and NOS expression in capsaicin-sensitive sensory neurones of the rat, similar to those described following axotomy.

Animals↗

PubMed1995

Distribution of acidic fibroblast growth factor mRNA-expressing neurons in the adult mouse central nervous system.

The distribution of acidic fibroblast growth factor (aFGF) mRNA-expressing neurons was studied throughout the adult mouse central nervous system (CNS) with in situ hybridization histochemistry using a radiolabelled synthetic oligodeoxynucleotide probe complementary to the mRNA of human aFGF. We report here a widespread distribution of aFGF mRNA in several defined functional systems of the adult mouse brain, whereby the highest levels of aFGF mRNA were found in large somatomotor neurons in the nuclei of the oculomotor, trochlear, abducens, and hypoglossal nerves; in the motoneurons of the ventral spinal cord and the special visceromotor neurons in the motor nucleus of the trigeminal nerve; and in the facial and ambiguus nuclei. Labelled perikarya were also detected in all central structures of the auditory pathway including the level of the inferior colliculus, i.e., the lateral and medial superior nuclei; the trapezoid, cochlear, and lateral lemniscal nuclei; and parts of the anterior colliculus. Furthermore, many aFGF-positive cell bodies were found in the vestibular system and other structures projecting to the cerebellum, in the deep cerebellar nuclei, in somatosensory structures of the medulla (i.e., in the gracile, cuneate, and external cuneate nuclei), as well as in the spinal nucleus of the trigeminal nerve. The findings that aFGF mRNA is expressed in all components of several well-defined systems (i.e., in sensory structures) as well as in central neurons that process sensory information and, finally, in some efferent projections point towards a concept of aFGF expression primarily within certain neuronal circuitries.

Animals↗

PubMed1995

Increase in alpha-CGRP and GAP-43 in aged motoneurons: a study of peptides, growth factors, and ChAT mRNA in the lumbar spinal cord of senescent rats with symptoms of hindlimb incapacities.

Sprague-Dawley rats develop progressive motor dysfunctions during the third year of life. We use this as a model to examine possible neuronal mechanism(s) that may cause motor impairments occuring during aging. In this study we have used indirect immunofluorescence histochemistry (IF) and in situ hybridization histochemistry (ISH) to study quantitatively and qualitatively the staining pattern and mRNA expression of calcitonin gene-related peptide (alpha-CGRP), growth-associated protein 43 (GAP-43), and acidic fibroblast growth factor (aFGF) in spinal lumbar motoneurons of young adult (2-3 months) and aged (30 months) Sprague-Dawley rats. In addition, mRNAs encoding choline acetyltransferase (ChAT), beta-CGRP, and cholecystokinin (CCK) were analyzed. All aged rats used in this study disclosed symptoms of hindlimb incapacity, ranging from mild weight-bearing insufficiency to paralysis of the hind limbs. The symptoms were confined to the musculature of the hindlimb and hip regions. Only a small number (approximately 15%) of the large motoneurons that innervate the hindlimb muscles were lost in those aged rats that had clinical symptoms of hindlimb motor incapacities. The remaining motoneurons expressed ChAT mRNA at levels similar to those of young adult rats. The vast majority of these motoneurons showed increased mRNA levels for alpha-CGRP and GAP-43. Aged motoneurons contained more CGRP like immunoreactivity (LI), but the number of immunoreactive neurons was smaller than in adult rats. GAP-43-LI could be detected in motoneurons in aged, but not in adult, rats. GAP-43-LI was always colocalized with CGRP-LI in aged motoneurons. Studies of individual aged rats revealed that the increase of GAP-43 mRNA-positive cell bodies occurred in cases with the most severe clinical symptoms, whereas the increase in alpha-CGRP was even evident in rats with mild symptoms. No alterations in content of aFGF-LI or aFGF mRNA could be detected in the aged rat, and the content of CCK and beta-CGRP mRNAs was also normal. The usefulness of this rat model for studies of neuromuscular aging and possible functional roles for GAP-43 and CGRP in plastic and regenerative processes during aging are discussed.

Aging↗

PubMed1995

Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome.

The drive on respiration mediated by the peripheral arterial chemoreceptors was assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/- 8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine exposure, an effect counteracted by blockade of peripheral dopamine type 2 receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and increased the expression of tyrosine hydroxylase (TH) in the carotid bodies, further suggesting that DA mediates the acute effect of nicotine on arterial chemoreceptor function. During postnatal development TH and DA2R mRNA levels in the carotid bodies decreased. Thus, nicotine from smoking may also interfere with the postnatal resetting of the oxygen sensitivity of the peripheral arterial chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this period. Collectively these effects of nicotine on the peripheral arterial chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate the protective chemoreflex response. These mechanisms may underlie the well-known relation between maternal smoking and sudden infant death syndrome.

Animals↗

PubMed1995

Fibroblast growth factors regulate calcitonin gene-related peptide mRNA expression in rat motoneurons after lesion and in culture.

In this study, we have investigated the effect of fibroblast growth factors (bFGF and FGF-5) and brain derived neurotrophic factor (BDNF) on the expression of calcitonin gene-related peptide (CGRP) in rat motoneurons in vivo and in vitro. Following sciatic nerve transection in adult rats, the levels of alpha-CGRP and beta-CGRP mRNA were up- and down-regulated respectively in axotomized motoneurons, revealed by in situ hybridization histochemistry. Local administration of 1 microgram bFGF was able to entirely abolish the up-regulation of alpha-CGRP mRNA, and to further down-regulate beta-CGRP. These effects, albeit less pronounced, were still evident with 0.2 micrograms bFGF. In contrast, bFGF did not attenuate the lesion-induced decrease of choline acetyltransferase (ChAT) mRNA. Administration of BDNF did not significantly alter the expression of CGRP or ChAT mRNA in axotomized motoneurons. Both alpha- and beta-CGRP mRNAs could be detected by PCR in enriched motoneuron cultures prepared from rat embryos at embryonic day 14-15. Comparing the amplification of alpha- and beta-CGRP mRNAs with that of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in parallel samples, we found that cultures treated with FGF-5 had a lower ratio of alpha- and beta-CGRP mRNA to GAPDH mRNA, than did control or BDNF-treated cultures. BDNF, on the other hand increased alpha-CGRP and decreased beta-CGRP mRNA levels, though these effects were moderate compared with the effects of FGF-5. The results obtained in this study suggest that members of the FGF family of growth factors influence the expression of CGRP in rat motoneurons, and that the increase of this neuropeptide induced by axotomy may, at least in part, be due to deprivation of these target-derived factors.

Animals↗