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W Tetzlaff

Publications and source records attributed to W Tetzlaff.

At least 37 records · Page 2Linked to original sources
PubMed2000

Caspase-3 is activated following axotomy of neonatal facial motoneurons and caspase-3 gene deletion delays axotomy-induced cell death in rodents.

In this report, we examined the possible functions of the cell death protease, caspase-3, in the axotomy-induced apoptosis of facial motoneurons in newborn rodents. Using in situ hybridization and Western blot, we found higher levels of caspase-3 mRNA and pro-caspase-3 protein expression in motoneurons of neonatal and 2-week-old rats than adult rats. Following facial motoneuron axotomy, caspase-3 mRNA and protein expression increased in motoneurons of both neonatal and adult rats. However, using an antibody directed to the activated form of the caspase-3 protease, we found that catalytically active caspase-3 was present only in axotomized neonatal motoneurons. As motoneurons in neonatal but not adult rodents are susceptible to axotomy-induced apoptosis, we hypothesized that caspase-3 may play a role in their demise. To determine the necessity of caspase-3 activation in axotomy-induced apoptosis, we counted the number of surviving motoneurons at 4 and 7 days following axotomy in wild type mice and caspase-3 gene-deleted mice. There were nearly three times more surviving motoneurons in caspase-3 gene-deleted mice than in wild type mice at both 4 days (mean 1074 vs. 464, P<0.005) and 7 days (mean 469 vs. 190, P<0.005) following injury, indicating a slower rate of death. Examination of the dying motoneurons using TUNEL staining (for fragmented DNA) and bisbenzimide staining (for nuclear morphology) revealed incomplete nuclear condensation in caspase-3-deficient motoneurons. These results demonstrate that caspase-3 activation plays important roles in the rapid demise of axotomized neonatal motoneurons.

Age Factors↗
PubMed1999

Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation of GAP-43, tubulins, and neurofilament-M.

Axotomized motoneurons regenerate their axons regardless of whether axotomy occurs proximally or distally from their cell bodies. In contrast, regeneration of rubrospinal axons into peripheral nerve grafts has been detected after cervical but not after thoracic injury of the rubrospinal tract. By using in situ hybridization (ISH) combined with reliable retrograde tracing methods, we compared regeneration-associated gene expression after proximal and distal axotomy in spinal motoneurons versus rubrospinal neurons. Regardless of whether they were axotomized at the iliac crest (proximal) or popliteal fossa (distal), sciatic motoneurons underwent highly pronounced changes in ISH signals for Growth Associated Protein 43 (GAP-43) (10-20x increase) and neurofilament M (60-85% decrease). In contrast, tubulin ISH signals substantially increased only after proximal axotomy (3-5x increase). To compare these changes in gene expression with those of axotomized rubrospinal neurons, the rubrospinal tract was transected at the cervical (proximal) or thoracic (distal) levels of the spinal cord. Cervically axotomized rubrospinal neurons showed three- to fivefold increases in ISH signals for GAP-43 and tubulins (only transient) and a 75% decrease for neurofilament-M. In sharp contrast, thoracic axotomy had only marginal effects. After implantation of peripheral nerve transplants into the spinal cord injury sites, retrograde labeling with the sensitive retrograde tracer Fluoro-Gold identified regenerating rubrospinal neurons only after cervical axotomy. Furthermore, rubrospinal neurons specifically regenerating into the transplants were hypertrophied and expressed high levels of GAP-43 and tubulins. Taken together, these data support the concept that, even if central nervous system (CNS) axons are presented with a permissive/supportive environment, appropriate cell body responses to injury are a prerequisite for CNS axonal regeneration.

Animals↗
PubMed1999

BDNF, but not NT-3, promotes long-term survival of axotomized adult rat corticospinal neurons in vivo.

Axotomy-induced death of corticospinal neurons (CSN) is prevented by intracotrical infusions of BDNF or NT-3 within the first week after axotomy. The present study examined whether this represents merely a delay of CSN death or whether BDNF and NT-3 can promote long-term survival of these neurons in vivo. The neurotrophins were infused for an initial period of 14 days to lesioned CSN which was followed by 28 days without treatment. BDNF was able to promote CSN survival for at least 42 days while NT-3 had no significant effect. These results suggest that initial BDNF treatment induces an endogamous mechanism that promotes survival of axotomized CSN without further exogenous neurotrophic factor supply. These findings may be important for the design of therapeutic strategies for motoneuron disease.

Animals↗
PubMed1998

Acetylcholinesterase gene expression in axotomized rat facial motoneurons is differentially regulated by neurotrophins: correlation with trkB and trkC mRNA levels and isoforms.

We examined the potential influences of muscle-derived neurotrophins on the acetylcholinesterase (AChE) gene expression of adult rat motoneurons. Seven days after facial nerve transection, both AChE mRNA and enzyme activity levels were markedly reduced in untreated and vehicle-treated facial motoneurons, suggesting positive regulation of motoneuron AChE expression by muscle-derived factors. Because skeletal muscle is a source of neurotrophin-3 (NT-3), NT-4/5, and BDNF, these neurotrophins were individually infused onto the proximal nerve stump for 7 d, beginning at the time of axotomy. The trkB ligands NT-4/5 and BDNF prevented the downregulation of AChE mRNA and enzymatic activity, as determined by in situ hybridization, biochemical assay, and histochemical visualization of enzyme activity. In contrast, NT-3 had limited effects, and NGF was without effect. Because motoneurons normally express both trkB and trkC receptors and the trkC ligand NT-3 is the most abundant muscle-derived neurotrophin, we investigated possible reasons for the limited effects of NT-3. In situ hybridization and reverse transcription-PCR both revealed a downregulation of trkC mRNA in axotomized motoneurons, which contrasted the upregulation of trkB expression. Furthermore, isoforms of trkC were detected carrying insertions within their kinase domains, known to limit certain trkC-mediated signal transduction pathways. Because the changes in trkB and trkC mRNA levels were not significantly altered by neurotrophin infusions, it is unlikely they were induced by loss of muscle-derived neurotrophins. These results demonstrate that NT-4/5 and BDNF stimulate AChE gene expression in motoneurons and support the concept that muscle-derived trkB ligands modulate the cholinergic phenotype of their innervating motoneurons.

Acetylcholinesterase↗
PubMed1998

Engines, accelerators, and brakes on functional spinal cord repair.

It is proposed that four essential goals should be met for functional repair after traumatic injury of the adult spinal cord. These include protecting neural tissue after injury and limiting secondary cell damage; replacing lost tissue with transplanted cell "bridges"; blocking the expression of intrinsic factors within the adult CNS that inhibit neural repair; and providing appropriate sensorimotor activity to enhance plasticity within surviving circuits, as well as consolidate any anatomical repair/regeneration. Included is a brief discussion on the approaches and limitations in the evaluation of functional spinal cord repair.

Animals↗
PubMed1998

Immediate-early gene expression in the brain of the thiamine-deficient rat.

Pyrithiamine-induced thiamine deficiency (PTD) in the rat is associated with neuronal loss in the thalamus and inferior colliculus. Recently, we were able to demonstrate the occurrence of apoptosis in the thalamus of these animals. Given that immediate-early genes (IEGs) participate in signal transduction pathways that mediate programmed cell death, the present study utilized in situ hybridization and immunohistochemistry to examine the expression of four IEGs (c-fos, c-jun, fos-B, and NGFI-A) during the progression of PTD. Elevated c-fos mRNA levels were initially observed in the posterior medial thalamus on d 12 of the deficiency. At the acute symptomatic stage (characterized by a loss of righting reflex on d 16-17), the posterior-medial thalamus exhibited increased mRNA for all genes examined, whereas the inferior colliculus demonstrated mRNA induction for c-fos, c-jun, and NGFI-A. Immunohistochemical analysis revealed that elevations of IEG mRNA associated with the acute symptomatic stage were consistently translated into protein in the thalamus. In contrast, whereas elevated Fos- and Jun-like immunoreactivity were detected in the inferior colliculus at this stage, NGFI-A-like immunoreactivity declined significantly below basal levels, suggesting a translational block. These results are consistent with our recent findings of apoptotic cell death, and indicate that differential patterns of IEG expression occur in the thalamus and inferior colliculus during PTD, which may contribute to the pathogenesis of this disorder.

Animals↗
PubMed1997

BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration.

Rubrospinal neurons (RSNs) undergo a marked atrophy in the second week after cervical axotomy. This delayed atrophy is accompanied by a decline in the expression of regeneration-associated genes such as GAP-43 and Talpha1-tubulin, which are initially elevated after injury. These responses may reflect a deficiency in the trophic support of axotomized RSNs. To test this hypothesis, we first analyzed the expression of mRNAs encoding the trk family of neurotrophin receptors. In situ hybridization revealed expression of full-length trkB receptors in virtually all RSNs, which declined 7 d after axotomy. Full-length trkC mRNA was expressed at low levels. Using RT-PCR, we found that mRNAs encoding trkC isoforms with kinase domain inserts were present at levels comparable to that for the unmodified receptor. TrkA mRNA expression was not detected in RSNs, and the expression of p75 was restricted to a small subpopulation of axotomized cells. In agreement with the pattern of trk receptor expression, infusion of recombinant human BDNF or NT-4/5 into the vicinity of the axotomized RSNs, between days 7 and 14 after axotomy, fully prevented their atrophy. This effect was still evident 2 weeks after the termination of BDNF treatment. Moreover, BDNF or NT-4/5 treatment stimulated the expression of GAP-43 and Talpha1-tubulin mRNA and maintained the level of trkB expression. Vehicle, NGF, or NT-3 treatment had no significant effect on cell size or GAP-43 and Talpha1-tubulin expression. In a separate experiment, infusion of BDNF also was found to increase the number of axotomized RSNs that regenerated into a peripheral nerve graft. Thus, in BDNF-treated animals, the prevention of neuronal atrophy and the stimulation GAP-43 and Talpha1-tubulin expression is correlated with an increased regenerative capacity of axotomized RSNs.

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PubMed1996

Reductions in motoneuronal neurofilament synthesis by successive axotomies: a possible explanation for the conditioning lesion effect on axon regeneration.

Axons regenerate more rapidly after a test lesion if they received a conditioning lesion. Previous work suggests that the cell body reaction to injury is responsible for this conditioning lesion effect. Here we examined the effects of the second, test lesion on the expression of the major cytoskeletal proteins, tubulin, actin, and neurofilament proteins. Using 2D-SDS-PAGE to separate these cytoskeletal proteins synthesized in the facial nucleus, along with in situ hybridization and RNA blotting to measure corresponding mRNA levels, we found that previous conditioning had little effect on actin or tubulin responses to a test lesion, but resulted in further decrease in neurofilament synthesis. Immunocytochemistry and electron microscopy revealed a greater loss of neurofilaments from the proximal conditioned axons, and axonal shrinkage. We suggest that the reduction in neurofilaments in the proximal axons of conditioned neurons reduces interference with tubulin transport. This may allow more tubulin to be transported more rapidly into the growing axon, to support the faster elongation rate of conditioned axons following a test lesion.

Animals↗
PubMed1996

NGF prevents further atrophy of cholinergic cells of the nucleus basalis due to cortical infarction in adult post-hypothyroid rats but does not restore cell size compared to euthyroid [correction of euthroid] rats.

We have tested the hypotheses that nerve growth factor treatment in adult post-hypothyroid rats can: (1) restore cross-sectional area of cholinergic cells of the nucleus basalis and (2) prevent further atrophy of these neurons following cortical infarction. In addition, we assessed the expression of p75NGFR and p140trkA mRNAs in the nucleus basalis cells of post-hypothyroid rats. Rats were rendered hypothyroid by the addition of propylthiouracil to their diet beginning on embryonic day 19 until the age of 1 month. At this time both the pups and their dams continued to receive 0.05% propylthiouracil in their diet and the pups were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and thyroxine levels were restored to normal by daily subcutaneous administration of physiological levels of thyroxine. Morphometric analysis identified atrophied nucleus basalis magnocellularis cholinergic cells at two ages, days 75 and 105, identified by in situ hybridization for p75NGFR and p140trkA mRNAs in methylene blue stained cells (day 75) and choline acetyltransferase immunostaining (day 105). The mean number of silver grains (pixels) per microns2 (mean +/- S.E.M.) of cell body cross-sectional area for p75NGFR mRNA in the nucleus basalis magnocellularis of euthyroid rats was 3.43 +/- 0.89, which was not statistically different from post-hypothyroid animals (4.02 +/- 1.07). A similar finding was noted for p140trkA mRNA: mean number of grains in the euthyroid group was 5.54 +/- 0.96 and was not statistically different from the post-hypothyroid group (6.32 +/- 1.45). Nerve growth factor treatment in adulthood (between days 75 and 82) did not restore cross-sectional area from early thyroid deprivation. However, it prevented further atrophy of nucleus basalis magnocellularis neurons following cortical devascularization inflicted in adulthood (day 75).

Acetylcholine↗
PubMed1996

BDNF and NT-3, but not NGF, prevent axotomy-induced death of rat corticospinal neurons in vivo.

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been identified as survival factors for adult axotomized rat corticospinal neurons (CSN) in vivo. Axotomy of corticospinal neurons at the level of the internal capsule induced death of 46% of the CSN within the first week after axotomy. The surviving population of CSN displayed severe atrophy with mean cross-sectional area 49% of their unlesioned contralateral counterparts 7 days after axotomy. Using in situ hybridization to assess the expression of the receptors for the family of neurotrophins, we found trkB and trkC but not trkA mRNA expression in CSN. Intraparenchymal application of BDNF or NT-3 at doses of 12 microg/day for 7 days via an osmotic minipump fully prevented the axotomy-induced death of CSN. Interestingly, no neuronal atrophy was seen after BDNF application while NT-3 had only a partial effect on the size of the axotomized CSN. Nerve growth factor did not prevent death or cell atrophy, consistent with lack of trkA mRNA expression in these neurons. These findings show that BDNF and NT-3 are survival factors for adult rat CSN in vivo, and may contribute to the development of therapeutic strategies aiming at the prevention of CSN degeneration in human motor neuron diseases.

Animals↗
PubMed1996

GAP-43 mRNA in mouse motoneurons undergoing axonal sprouting in response to muscle paralysis of partial denervation.

To test the hypothesis that collateral sprouting of motoneurons can occur without the intervention of metabolic changes in the cell body, we examined the levels of growth-associated protein 43 (GAP-43) mRNA in mouse motoneurons induced to sprout by muscle inactivity (following marcaine or botulinum toxin treatment) or by partial denervation. GAP-43 mRNA was selected as an appropriate marker for cell body metabolic changes because it is expressed at low levels in mature motoneurons, but is strongly expressed during developmental or regenerative axonal growth in motoneurons. Sprouting motoneurons were identified by retrograde labelling with fluorescent tracers applied to the muscle in which sprouting occurred. Both a full-length cDNA probe and an oligonucleotide probe were used for in situ hybridization. We were unable to detect any significant increases in GAP-43 mRNA levels in fluorescent motoneurons after any treatment, except 4 days after partial denervation (but not at 2 or 8 days). This amounted to a 1.6-fold increase in signal level compared to control motoneurons, while presumed axotomized motoneurons in the same spinal cords displayed on average an 8. 7-fold increase. We conclude that collateral sprouting can occur in motoneurons without a detectable increase in cell body levels of GAP-43 mRNA. The modest increase observed in the 4-day partial denervation situation may be a response to the more vigorous and extensive nodal axonal sprouting occurring in these motoneurons. Our results do not deny a role for pre-existing GAP-43 in collateral sprouting, but support the hypothesis that sprouting can occur in motoneurons without necessarily requiring increase GAP-43 mRNA levels in the cell body.

Animals↗
PubMed1996

Increased expression of BDNF and trkB mRNA in rat facial motoneurons after axotomy.

Motoneurons of the adult survive after axotomy even though they are deprived of putative target derived trophic factors. Alternative sources of trophic support may substitute. In this study we test the hypothesis that the immediate environment of the motoneuronal cell body or the cell body itself increases the production of trophic factors after axonal injury. Using in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), we report that after axotomy, rat facial motoneurons increase the expression of mRNA for brain-derived neurotrophic factor (BDNF) and its receptor trkB. After transection of the facial nerve, we measured a 2- to 4-fold increase in BDNF mRNA expression which had its onset between 3 and 8 h after injury. The BDNF mRNA levels peaked at approximately 1-2 days and gradually declined thereafter to return to contralateral levels within 7 days of injury. Western blotting revealed a several-fold increase in BDNF as early as 24 h, which subsequently reached a maximum in approximately 5-7 days and was still sustained at 2 weeks post-axotomy. Using exon-specific primers, we determined that the increase in BDNF mRNA is largely due to an increased expression from the promoters of exons IV and III, and to a lesser extent from exons I and II. Analysing the mRNA expression for the BDNF receptor, trkB, we found a 2- to 3-fold increase in full-length trkB mRNA expression starting 2 days after axotomy which lasted 2-3 weeks. These findings suggest that BDNF might act locally on axotomized motoneurons in an autocrine fashion, providing support for axotomized motoneurons during the first weeks after axotomy.

Animals↗
PubMed1995

Cell body response to injury in motoneurons and primary sensory neurons of a mutant mouse, Ola (Wld), in which Wallerian degeneration is delayed.

We examined the response to axon injury in the facial motoneurons and dorsal root ganglion (DRG) neurons of C57BL/Ola (Wld) mice, compared with the responses of C57BL/6J mice. The peripheral nerves of Ola mutants undergo remarkably slowed and muted Wallerian degeneration after injury. The increase in GAP-43 mRNA levels in facial motoneurons and DRG neurons was similar in both strains of mice, as was the initial decrease in medium-weight neurofilament (NFM) mRNA in facial motoneurons, and the increase in JUN immunoreactivity in both types of neurons. However, the subsequent recovery to normal low levels of JUN and GAP-43 mRNA expression and high levels of NFM mRNA was delayed in Ola motoneurons. We ascribe this delay to the slow regeneration and target reinnervation of facial axons in the Ola mice. These results show that absence of rapid Wallerian degeneration does not affect the initial cell body response to axonal injury. They also provide further evidence that restoration of normal levels of expression of GAP-43 and NFM mRNAs is dependent on target reinnervation and/or trophic factors provided by the distal nerve. Impaired regeneration in the Ola mouse does not seem to be a consequence of a defective cell body response to injury, and our results illustrate the general principle that, even if there is a vigorous cell body response to injury, normal axonal regeneration requires the additional provision of a favorable environment for growth.

Animals↗
PubMed1995

C-fos mediates antipsychotic-induced neurotensin gene expression in the rodent striatum.

The ubiquitous inducibility of the immediate-early gene c-fos in the central nervous system has led to the search for downstream genes which are regulated by its product, Fos. Recent evidence suggests that c-fos induction by a single injection of the classical antipsychotic haloperidol may contribute to the subsequent increase in neurotensin gene expression in the rodent striatum. Consistent with this proposal, in the present study haloperidol-induced Fos-like immunoreactivity and neurotensin/neuromedin N messenger RNA were found to be expressed by the same population of striatal neurons. Moreover, inhibition of haloperidol-induced c-fos expression by intrastriatal injection of antisense phosphorothioate oligodeoxynucleotides complimentary either to bases 109-126 or 127-144 of c-fos attenuated the subsequent increase in neurotensin/neuromedin N messenger RNA. However, injection of a sense phosphorothioate oligodeoxynucleotide corresponding to bases 127-144 of c-fos did not reduce haloperidol-induced c-fos or neurotensin/neuromedin N expression. Furthermore, constitutive expression of Jun-like immunoreactivity in the striatum was not reduced by either the sense or antisense phosphorothioate oligodeoxynucleotides. Similarly, the sense and antisense phosphorothioate oligodeoxynucleotide failed to reduce proenkephalin messenger RNA, which is located in the same striatal neurons that express haloperidol-induced neurotensin/neuromedin N messenger RNA, which is located in the same striatal neurons that express haloperidol-induced neurotensin/neuromedin N messenger RNA. Lastly, haloperidol-induced increases in nerve growth factor I-A-, JunB- and FosB-like immunoreactivity and fosB messenger RNA were not decreased by intrastriatal injection of either the sense or antisense phosphorothioate oligodeoxynucleotides. These results indicate that the antisense phosphorothioate oligodeoxynucleotides attenuated haloperidol-induced neurotensin/neuromedin N expression by selectively reducing c-fos expression and emphasize the potential importance of immediate-early gene induction in the mechanism of action of this antipsychotic drug.

Animals↗
PubMed1995

Differential expression of p140trk, p75NGFR and growth-associated phosphoprotein-43 genes in nucleus basalis magnocellularis, thalamus and adjacent cortex following neocortical infarction and nerve growth factor treatment.

A loss of target-derived neurotrophic factors is hypothesized to be one of the major determinants of central nervous system neuronal degeneration. In order to obtain further insight into early neuronal responses to injury, lesion-induced alterations in the expression of high- and low-affinity nerve growth factor receptors, as well as growth-associated phosphoprotein-43 genes in nucleus basalis magnocellularis, thalamic and neocortical neurons were studied. For this purpose, unilateral cortical devascularization operations were conducted on adult rats. Animals received i.c.v. infusions of vehicle or nerve growth factor (12 micrograms/day) and were killed at one, three, seven and 15 days post-lesion. In situ hybridization studies using 35S-labelled oligonucleotide probes for p75NGFR, p140trk and growth-associated phosphoprotein-43 messenger RNAs reveals that these genes were differentially regulated following the lesion. In the nucleus basalis magnocellularis ipsilateral to the lesion, p140trk gene expression significantly decreased on days 3 and 7, while p75NGFR messenger RNA initially increased on day 3 and decreased on days 7 and 15 after lesion. GAP-43 messenger RNA levels were significantly increased in the nucleus basalis magnocellularis on post-lesion days 3 and 7. Moreover, in contrast to p75NGFR or 140trk, growth-associated phosphoprotein-43 messenger RNA levels were significantly increased in pyramidal neurons located in the remaining cortex adjacent to the cortical lesion at all time points. In the lateral and ventroposterior nuclei of the thalamus, growth-associated phosphoprotein-43 messenger RNA level was slightly increased on days 1 and 3 and was dramatically decreased, significantly below the levels in sham-operated controls, on post-lesion days 7 and 15. During nerve growth factor application, the level of p140trk messenger RNA in the lesioned nucleus basalis magnocellularis returned to values observed in the contralateral nucleus basalis magnocellularis while p75NGFR messenger RNA was increased above values noted in all animals not treated with nerve growth factor. Nerve growth factor treatment did not affect the expression of growth-associated phosphoprotein-43 messenger RNA in any of the areas studied. p140trk messenger RNA was not up-regulated during the time that nerve growth factor was applied, as observed for p75NGFR, but only eight days after interrupting nerve growth factor treatment. Three cell types, nucleus basalis magnocellularis, cortical pyramidal and thalamic neurons, were probably affected in different ways by the devascularization with respect to lesion extent. Consequently, the remaining number of synaptic contacts in each of these brain areas is most likely different which may lead to a differential regulation of growth-associated phosphoprotein-43 messenger RNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Neural regulation of acetylcholinesterase mRNAs at mammalian neuromuscular synapses.

We examined the role of innervation on acetylcholinesterase (AChE) gene expression within mammalian skeletal muscle fibers. First, we showed the selective accumulation of AChE mRNAs within the junctional vs extrajunctional sarcoplasm of adult muscle fibers using a quantitative reverse transcription PCR assay and demonstrated by in situ hybridization experiments that AChE transcripts are concentrated immediately beneath the postsynaptic membrane of the neuromuscular junction. Next, we determined the influence of nerve-evoked activity vs putative trophic factors on the synaptic accumulation of AChE mRNA levels in muscle fibers paralyzed by either surgical denervation or selective blockage of nerve action potentials with chronic superfusion of tetrodotoxin. Our results indicated that muscle paralysis leads to a marked decrease in AChE transcripts from the postsynaptic sarcoplasm, yet the extent of this decrease is less pronounced after tetrodotoxin inactivation than after denervation. These results suggest that although nerve-evoked activity per se appears a key regulator of AChE mRNA levels, the integrity of the synaptic structure or the release of putative trophic factors contribute to maintaining the synaptic accumulation of AChE transcripts at adult neuromuscular synapses. Furthermore, the pronounced downregulation of AChE transcripts in paralyzed muscles stands in sharp contrast to the well-documented increase in nicotinic acetylcholine receptor mRNAs under these conditions, and indicates that expression of the genes encoding these two synaptic proteins are subjected to different regulatory mechanisms in adult muscle fibers in vivo.

Acetylcholinesterase↗
PubMed1993

Proximal and distal impairments in rat forelimb use in reaching follow unilateral pyramidal tract lesions.

Although it was once thought that the corticospinal (pyramidal) tract was the main substrate of voluntary movement, the extent to which it is involved in the control of proximal vs. distal musculature, independent finger movements, and movements characteristic of different species of animals now is unclear. The objective of this study was to examine the effects of pyramidal tract lesions on skilled forelimb use in rats. In addition, cell morphology in motor cortex following lesions was examined. Naive and trained rats received unilateral pyramidal sections just rostral to the pyramidal decussation. Performance was assessed and filmed on two reaching tasks. Measures of reaching consisted of success in obtaining food, kinematic analysis of limb trajectory and velocity, and qualitative evaluation of 10 movement components comprising a reach. Pyramidal tract lesions only impaired reaching for single food pellets. Almost all movements comprising a reach, except digit opening, were impaired, including lifting, aiming, pronating and supinating the limb, and releasing food. Although success in limb use was unchanged over the 180 day observation period, there were significant improvements in the qualitative features of limb use. Histologically, the morphology of pyramidal cells in the forelimb area ipsilateral to the lesion seemed normal. Rats with additional damage to adjacent structures, such as the medial lemniscus and olivary complex, were much more severely impaired on the reaching tasks, and displayed similar impairments as judged by qualitative and kinematic measures. The results demonstrate that a number of movements involved in independent limb use are chronically impaired by pyramidal tract lesions in the rat. Nevertheless, significant use of the limb is possible, due perhaps to both the contribution of extrapyramidal motor systems and the influence of the remaining pyramidal system through its extrapyramidal connections. The results not only show that the rat pyramidal tract supports functions very similar to those of primates and thus might provide a good model for some aspects of pyramidal tract dysfunctions, but also they argue that the pyramidal tract is involved in both proximal and distal limb movements.

Animals↗