Biomedical subjects

K D Anderson

Publications and source records attributed to K D Anderson.

At least 55 records · Page 3Linked to original sources

PubMed1998

Apoptosis and DNA damage in type 2 alveolar epithelial cells cultured from hyperoxic rats.

Apoptosis is a genetically controlled cellular response to developmental stimuli and environmental insult that culminates in cell death. Sublethal hyperoxic injury in rodents is characterized by a complex but reproducible pattern of lung injury and repair during which the alveolar surface is damaged, denuded, and finally repopulated by type 2 alveolar epithelial cells (AEC2). Postulating that apoptosis might occur in AEC2 after hyperoxic injury, we looked for the hallmarks of apoptosis in AEC2 from hyperoxic rats. A pattern of increased DNA end labeling, DNA laddering, and induction of p53, p21, and Bax proteins, strongly suggestive of apoptosis, was seen in AEC2 cultured from hyperoxic rats when compared with control AEC2. In contrast, significant apoptosis was not detected in freshly isolated AEC2 from oxygen-treated rats. Thus the basal culture conditions appeared to be insufficient to ensure the ex vivo survival of AEC2 damaged in vivo. The oxygen-induced DNA strand breaks were blocked by the addition of 20 ng/ml of keratinocyte growth factor (KGF) to the culture medium from the time of plating and were partly inhibited by Matrigel or a soluble extract of Matrigel. KGF treatment resulted in a partial reduction in the expression of the p21, p53, and Bax proteins but had no effect on DNA laddering. We conclude that sublethal doses of oxygen in vivo cause damage to AEC2, resulting in apoptosis in ex vivo culture, and that KGF can reduce the oxygen-induced DNA damage. We speculate that KGF plays a role as a survival factor in AEC2 by limiting apoptosis in the lung after acute hyperoxic injury.

Animals↗

PubMed1998

Contractility, transforming growth factor-beta, and plasmin in fetal skin fibroblasts: role in scarless wound healing.

The early fetus responds to cutaneous wounds in a fundamentally different way from the adult; fetal wounds heal without scars. Wound contraction is a vital component of wound healing. The cytokine transforming growth factor (TGF)-beta promotes wound contraction and can be activated by the serine protease plasmin. Herein, we explored whether murine skin fibroblast contractile properties, TGF-beta, and plasmin formation are developmentally regulated. Our results showed that early fetal mouse embryonic day 15 skin fibroblasts contracted a collagen gel less, secreted less active and total TGF-beta, and generated less plasmin than either late fetal (embryonic day 17) or adult skin fibroblasts. Furthermore, there was a slight positive correlation between the formation of plasmin and the level of activation of TGF-beta. We conclude that early fetal mouse skin fibroblasts contract a collagen gel and secrete and activate TGF-beta to a lesser extent than do late fetal and adult skin fibroblasts. We speculate that the fetal skin fibroblast undergoes a developmental transition that causes wounds in mouse to contract at or after embryonic day 17. Further, this developmental transition is influenced by growth factor-fibroblast interactions and coincides with the emergence of the skin fibroblast's ability to generate plasmin and activate TGF-beta.

Animals↗

PubMed1997

Characterization of a full-length cDNA for rabbit factor X.

A 300 bp probe generated by the PCR was derived from rabbit genomic DNA using primers from a highly conserved region of the DNA for human factor X (HFX). The probe was used in northern blot analysis of liver RNA to demonstrate an mRNA species of 1.6 kb for the rabbit factor X and subsequently for isolation and characterization of the cDNA for rabbit factor X (RFX) from a lambda Zap II cDNA library generated from rabbit liver mRNA. The cDNA contains 22 bases upstream from the 5'-translation initiation codon, 1470 nucleotides of open reading frame, a stop codon and a 3' poly (A) tail. The cDNA codes for a 40-residue signal/propeptide region, followed by a 447-residue mature protein. The deduced amino acid sequence shows a high degree of homology with the sequence of HFX. Inhibitory peptides derived from interactive sites of HFX for activators, cofactor and substrate exerted degrees of inhibition of RFX activation which showed a dependence on extent of homology with the corresponding regions of RFX.

Amino Acid Sequence↗

PubMed1997

Cell cycle in alveolar epithelial type II cells: integration of Matrigel and KGF.

The regulation of cell cycle control in alveolar epithelial type II cells (AEC2) in response to peptide growth factors and extracellular matrix signals is not well understood. Herein, we have determined that, in adult rat AEC2 in primary culture on Engelbreth-Holm-Swarm biomatrix (Matrigel) in the presence of keratinocyte growth factor, the expression of key cell cycle control elements, including cyclins A and D and cyclin-dependent kinases (cdk) 1 and 4, is increased and that retinoblastoma protein (pRb) phosphorylation is also increased, with a corresponding decrease in the expression of p53 and the cdk inhibitors (cdkis) p21WAF1/CIP1 and p27KIP-1 compared with cells cultured on plastic. The Matrigel biomatrix-KGF culture conditions were also associated with an enhanced proliferative response, as measured by fluorescent-activated cell sorter analysis, thymidine incorporation into DNA, and proliferating cell nuclear antigen expression. This enhanced proliferation occurred with neither a soluble extract of Matrigel biomatrix nor with other simple biological matrices. We conclude that coordinated induction of key cyclins and cdks, with the concomitant suppression of key negative cell cycle regulators, occurs in AEC2 on Matrigel biomatrix in the presence of KGF. We speculate that the balance between cyclin and cdk activation and cdki suppression in AEC2 serves to integrate the combined influences of biomatrix and KGF signaling on pRb phosphorylation, thereby controlling transit through S phase of the cell cycle. Conversely, AEC2 express high levels of cdkis and p53 at rest in G1 phase. The latter finding may explain the quiescent state of normal adult AEC2 in vivo.

Animals↗

PubMed1997

Cyclin D1 antisense RNA destabilizes pRb and retards lung cancer cell growth.

To investigate the role of cyclin D1 in the regulation of lung cancer cell growth, we created five stably transfected cell lines carrying a cyclin D1 antisense construct. The transfected cells exhibited a marked decrease in the rate of cell growth, in contrast to the original lines (A549 and NCI-H441). The expression of several cell cycle-regulating proteins, including cyclin A, the cyclin-dependent kinases (cdk) 2 and cdk4, in addition to cyclin D1 itself, was markedly decreased. The expression of one cdk inhibitor, p21WAF1/CIP1, increased in the A549-derived cell lines. A specific target of cyclin D1 activity, the growth-suppressing product of the retinoblastoma gene, pRb, exhibited decreased expression and a decreased level of phosphorylation in the transfected cells. Decreased expression of pRb due to a significant increase in its turnover rate suggested that the stability of the protein may depend on phosphorylation by cyclin D1-dependent cdk activity. In addition to the impact on pRb stability, decreased expression of cyclin D1 induced susceptibility to cell death after withdrawal of exogenous growth factors in the antisense transfected cell lines, a response that was not observed in the original cancer cell lines. We conclude that abrogation of cyclin D1 overexpression in lung cancer cells disrupts several key pathways that are required for uncontrolled cell growth and induces those that lead to cell death after growth factor deprivation. Therefore, we speculate that use of antisense cyclin D1 expression in appropriate gene vectors could be a useful method for retarding lung cancer cell growth in accessible tumors such as those of the lung epithelium.

CDC2-CDC28 Kinases↗

PubMed1997

Factor VII C329R: a variant with a disrupted disulfide bond in the catalytic domain.

We report a novel mutation within the coagulation factor VII gene associated with a dysfunctional procoagulant factor VII (12% of normal plasma factor VII activity; 50% of normal plasma factor VII antigen level). Using heteroduplex analysis and subsequent sequencing, we identified a thymine-10,902 to cytosine mutation within exon eight of the factor VII gene, encoding for a substitution of arginine for cysteine-329 (factor VII C329R) within the heavy chain of factor VII. This substitution disrupts a disulfide bond within the factor VII catalytic domain and might cause altered conformation of the active site triad.

Cytosine↗

PubMed1996

Ciliary neurotrophic factor protects striatal output neurons in an animal model of Huntington disease.

Huntington disease is a dominantly inherited, untreatable neurological disorder featuring a progressive loss of striatal output neurons that results in dyskinesia, cognitive decline, and, ultimately, death. Neurotrophic factors have recently been shown to be protective in several animal models of neurodegenerative disease, raising the possibility that such substances might also sustain the survival of compromised striatal output neurons. We determined whether intracerebral administration of brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, or ciliary neurotrophic factor could protect striatal output neurons in a rodent model of Huntington disease. Whereas treatment with brain-derived neurotrophic factor, nerve growth factor, or neurotrophin-3 provided no protection of striatal output neurons from death induced by intrastriatal injection of quinolinic acid, an N-methyl-D-aspartate glutamate receptor agonist, treatment with ciliary neurotrophic factor afforded marked protection against this neurodegenerative insult.

Animals↗

PubMed1996

Light and electron microscopic immunohistochemical study of dopaminergic terminals in the striatal portion of the pigeon basal ganglia using antisera against tyrosine hydroxylase and dopamine.

A dopaminergic projection from the midbrain to the striatal portion of the basal ganglia is present in reptiles, birds, and mammals. Although the ultrastructure of these fibers and terminals within the striatum has been studied extensively in mammals, little information is available on the ultrastructure of this projection in nonmammals. In the present study, we used immunohistochemical labeling with antibodies against tyrosine hydroxylase (TH) or dopamine (DA) to study the dopaminergic input to the striatal portion of the basal ganglia in pigeons (i.e., lobus parolfactorius and paleostriatum augmentatum). At the light microscopic level, the anti-TH and anti-DA revealed a similar abundance and distribution of numerous labeled fine fibers and varicosities within the striatum. In contrast, the use of an antidopamine beta-hydroxylase antiserum (which labels only adrenergic and noradrenergic terminals) labeled very few striatal fibers, which were restricted to visceral striatum. These results demonstrate that anti-TH mainly labels dopaminergic terminals in the striatum. At the electron microscopic level, the anti-TH and anti-DA antisera labeled numerous axon terminals within the striatum (15-20% of all striatal terminals). These terminals tended to be small (with an average length of 0.6 microns) and flattened, and their vesicles tended to be small (35-60 nm in diameter) and pleomorphic. About 50% of the terminals were observed to make synaptic contacts in the planes of section examined, and nearly all of these synaptic contacts were symmetric. Both TH+ and DA+ terminals typically contacted dendritic shafts or the necks of dendritic spines, but a few contacted perikarya. No clear differences were observed between TH+ and DA+ terminals within medial striatum (whose neurons project to the nigra in birds) or between TH+ and DA+ terminals within lateral striatum (whose neurons project to the pallidum in birds). In addition, no differences were observed between medial and lateral striata in either TH+ or DA+ terminals. Thus, there is no evident difference in pigeons between striatonigral and striatopallidal neurons in their dopaminergic innervation. Our results also indicate that the abundance, ultrastructural characteristics, and postsynaptic targets of the midbrain dopaminergic input to the pigeon striatum are highly similar to those in mammals. This anatomical similarity is consistent with the pharmacologically demonstrable similarity in the role of the dopaminergic input to the striatum in birds and mammals.

Animals↗

PubMed1996

Can continuity-of-care requirements for surgery residents be demonstrated in the current teaching environment?

In 1994, the Residency Review Committee in Surgery began evaluating the ability of programs to provide adequate continuity-of-care experiences to residents, based on 6 criteria requiring resident participation in each phase of a surgical patient's care. The Residency Review Committee document further described resident and patient experiences as being synonymous. No previous studies were found that examined the 6 criteria or compared them with the patient's experience with continuity. Study objectives were 2-fold: (1) to assess the 6 required continuity-of-care experiences provided to general surgery residents and (2) to compare resident experiences to the patient's experience with continuity. Surgery residents from 2 academic years, representing each postgraduate year, were studied. Patients had (1) undergone an operation involving a resident and (2) remained hospitalized for longer than 24 hours but less than 10 days. Data were collected from a retrospective randomized review of each patient's medical records. Of the 114 cases, 23.7% showed that the same resident participated in all phases of care. In the remaining cases, residents provided preoperative care in 70.2%, directed the postoperative hospitalized care in 86.8%, and provided postdischarge care in 37.7%. Patients saw an average +/- SD of 4.6 +/- 1.5 surgical providers during the entire course of their surgical care. In conclusion, continuity experiences were provided to surgery residents in varying quantities and combinations, with one quarter of the residents experiencing "perfect continuity." Resident continuity experiences and patient continuity were not synonymous. Although improved medical record documentation may have enhanced these results, continuity-of-care remains difficult to demonstrate in view of the current surgery teaching environment.

Continuity of Patient Care↗

PubMed1996

Neurotrophin-4/5 maintains the cholinergic phenotype of axotomized septal neurons.

We examined the effect of intraseptal or intracerebroventricular (i.c. v.) infusions of NT-4/5 or intraseptal infusions of NGF on the level of immunohistochemical staining of choline acetyltransferase (ChAT)and the low-affinity nerve growth factor receptor (LNGFR)in the rat medial septum following unilateral transection of the fimbria. The extent of cell loss in the septum ipsilateral to the lesion, determined by cell counts of ChAT-immunopositive neurons and expressed as a ratio comparing the lesioned to the intact sides, was 0.28 in animals that received an infusion of phosphate-buffered saline (PBS). The ratios were 0.97 and 1.07 in animals that received an infusion of NT-4/5 into the ipsilateral ventricle and septum respectively. Septal infusions of NGF produced a ratio of ChAT-immunopositive cells of 1.03. The ratios of LNGFR-immunopositive neurons increased from 0.50 in PBS-infused animals to 0.79 and 0.83 in animals infused with NT-4/5 via the i.c. v. infusion of NT-4/5 or septal infusion of NT-4/5 or NGF. As determined by immunohistochemical staining, NT-4/5 infused into the lateral ventricle was detected in the periventricular portions of the forebrain ipsilateral to the infusion, while NT-4/5 or NGF infused intraseptally was detected in much of the septum, bilaterally. Furthermore, exogenous NT-4/5 or NGF was detected in numerous neuronal perikarya in the medial septal and diagonal band nuclei. These data demonstrate that, as with NGF, i.c.v. as well as septal infusions of NT-4/5 can maintain the phenotype of basal forebrain cholinergic neurons following axotomy.

Animals↗

PubMed1995

An ultrastructural double-label immunohistochemical study of the enkephalinergic input to dopaminergic neurons of the substantia nigra in pigeons.

Electron microscopic immunohistochemical double-label studies were carried out in pigeons to characterize the ultrastructural organization and postsynaptic targets of enkephalinergic (ENK+) striatonigral projection. ENK+ terminals in the substantia nigra were labeled with antileucine-enkephalin antiserum by using peroxidase-antiperoxidase methods, and dopaminergic neurons were labeled with anti-tyrosine hydroxylase antiserum by using silver-intensified immunogold methods. ENK+ terminals on dopaminergic neurons were equal in abundance to ENK+ terminals on nondopaminergic neurons, although the former were typically somewhat smaller than the latter (mean size: 0.50 vs. 0.75 micron, respectively). ENK+ terminals were evenly distributed on the cell bodies and dendrites of dopaminergic neurons, and they were evenly distributed on dendrites but rare on perikarya of nondopaminergic neurons. Transection of the basal telencephalic output revealed that 75% of the nigral ENK+ terminals were of basal telencephalic origin. These telencephalic ENK+ terminals included over 80% of those smaller than 0.80 micron on dopaminergic neurons and smaller than 1.0 micron on nondopaminergic neurons, and none greater than this in size. Both telencephalic and the nontelencephalic ENK+ nigral terminals made predominantly symmetric synapses on nigral neurons. Although the basal telencephalic ENK+ terminals uniformly targeted dendrites and perikarya, nontelencephalic ENK+ terminals seemed to avoid perikarya. The results indicate that ENK+ striatonigral neurons in birds may directly influence both dopaminergic and nondopaminergic neurons of the substantia nigra. Based on similar data for substance P-containing striatonigral terminals, the roles of enkephalin and substance P in influencing nigral dopaminergic neurons may differ slightly, as they appear to target preferentially different portions of dopaminergic neurons. The overall results in pigeons are similar to those for ENK+ terminals in the ventral tegmental area in rats, suggesting that the synaptic organization of the ENK+ input to the tegmental dopaminergic cell fields is similar in mammals and birds.

Animals↗

PubMed1995

Differential distribution of exogenous BDNF, NGF, and NT-3 in the brain corresponds to the relative abundance and distribution of high-affinity and low-affinity neurotrophin receptors.

To evaluate effective means for delivering exogenous neurotrophins to neuron populations in the brain, we compared the distribution and transport of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) following intracerebral delivery. Rats received an injection of radioiodinated or unlabeled neurotrophin into the lateral ventricle and were killed humanely after 1.5-24 hours. Other rats received continuous infusion of unlabeled neurotrophin into the lateral ventricle, the striatum, or the hippocampus for 3-14 days. The neurotrophins were detected by autoradiography or immunohistochemistry. There were striking differences between BDNF, NGF, and NT-3 in their penetration through brain tissue. These differences occurred regardless of the site or method of delivery, but were most pronounced following a bolus intracerebroventricular (ICV) injection. After ICV injection, NGF was widely distributed in tissues around the ventricles and at the surface of the brain, whereas the penetration of BDNF into brain tissue was distinctly less than that of NGF, and the penetration of NT-3 was intermediate. An ICV injection of NGF produced prominent but transient labeling of cells that contain the low-affinity NGF receptor, whereas an injection of BDNF prominently labeled the ventricular ependyma. During ICV infusion (12 micrograms/day), the distribution of BDNF was no greater than that observed after a 12-micrograms bolus injection. A sixfold increase in the amount of BDNF infused (72 micrograms/day) produced a more widespread distribution in the brain and doubled the depth of penetration into periventricular tissues near the cannula. Corresponding to their differences in penetration, NGF was retrogradely transported by basal forebrain cholinergic neurons after ICV or intrastriatal delivery, whereas NT-3 was transported by a few basal forebrain neurons after ICV delivery, and BDNF was rarely detected in neurons after ICV delivery. Delivery of BDNF directly to the striatum or the hippocampus labeled numerous neurons in nuclei afferent to these structures. In situ hybridization studies confirmed that the high-affinity BDNF receptor (TrkB) was much more widely expressed in neurons than was the high-affinity NGF receptor (TrkA). Moreover, mRNA for truncated forms of TrkB was expressed at high levels in the ependyma, the choroid epithelium, and the gray matter. It is likely that binding of BDNF to TrkB, which appears to be more abundant and ubiquitous than TrkA, restricts the diffusion of BDNF relative to that of NGF.

Animals↗

PubMed1995

Experience with abdominal wall closure for patients with congenital diaphragmatic hernia repaired on ECMO.

Congenital diaphragmatic hernia (CDH) and its attendant lack of abdominal domain can create major technical challenges with respect to diaphragmatic and abdominal wall reconstruction, especially in seriously ill infants who require extracorporeal membrane oxygenation (ECMO). The authors reviewed the medical records of all infants with CDH repaired on ECMO at their institution (group 1, 15 patients), and compared them with infants having CDH repair before ECMO (group 2, 20 patients) and with those who had CDH repair but did not require ECMO (group 3, 15 patients). Thirty-seven of 50 patients survived (74%): 10 in group 1, 12 in group 2, and all 15 in group 3. There was a statistically significant difference (P < .001) with respect to the requirement of a polytetrafluoroethylene (PTFE) diaphragmatic patch for patients in group 1 versus those in both groups 2 and 3. There was also a significant difference in the number of patients in whom the abdomen could not be closed (P < .001 for group 1 v groups 2 and 3). Infants who require ECMO before CDH repair are more likely to have large diaphragmatic defects that require prosthetic reconstruction, and abdominal wall closure problems resulting from loss of abdominal domain, which further complicate the management of the physiological derangements from pulmonary hypoplasia and persistent pulmonary hypertension.

Abdominal Muscles↗

PubMed1995

Thalamostriatal projection neurons in birds utilize LANT6 and neurotensin: a light and electron microscopic double-labeling study.

Based on its location, connectivity and neurotransmitter content, the dorsal thalamic zone in birds appears to be homologous to the intralaminar, midline, and mediodorsal nuclear complex in the thalamus of mammals. We investigated the neuroactive substances used by thalamostriatal projection neurons of the dorsal thalamic zone in the pigeon. Single-labeling experiments showed that many neurons in the dorsal thalamic zone are immunoreactive for neurotensin and the neurotensin-related hexapeptide, (Lys8,Asn9)NT(8-13) (LANT6). Double-labeling experiments, using the retrograde fluorescent tracer, FluoroGold, combined with fluorescence immunocytochemistry for either LANT6 or neurotensin, showed that neurotensin- and LANT6-containing neurons in the dorsal thalamic zone project to the striatum of the basal ganglia. Immunofluorescence double-labeling experiments showed that neurotensin and LANT6 are often (possibly always) co-expressed in neurons in the dorsal thalamic zone. Electron microscopic immunohistochemical double-labeling showed that LANT6 terminals in the striatum make asymmetric contacts with heads of spines labeled for substance P and heads of spines not labeled for substance P, suggesting that these terminals synapse with both substance P-containing and non-substance P-containing medium spiny striatal projection neurons. These findings indicate that LANT6 and neurotensin may be utilized as neurotransmitters in thalamostriatal projections in birds and raise the possibility that this may also be the case in other amniotes.

Animals↗

PubMed1995

The relationship between career satisfaction and fellowship training in academic surgeons.

BACKGROUND: Academic surgeons make various important decisions about their careers; however, little is known about the relationships between fellowship training, career development issues, and academic responsibilities. METHODS: Surgeon members of the Association for Surgical Education were surveyed about career development issues. Three hundred ninety-two (75.2%) surgeons responded. RESULTS: An exploratory factor analysis of the career development issues revealed four career development factors. Statistically significant differences were found between types of fellowship training and the career development factors. Nonfellowship-trained and clinical-fellowship-trained surgeons spend their time similarly to physicians in other specialties. Research-fellowship-trained surgeons spent significantly more time doing research, had fewer concerns about professional confidence, and expressed greater satisfaction with their careers. CONCLUSION: There is a relationship between career development issues, fellowship training, and type of fellowship training. Attention to these issues may be important in recruiting and retaining academic surgeons.

Career Mobility↗

PubMed1995

Experience with surgical resident training in a combined program in plastic surgery.

Healthcare reform may impact graduate medical education (GME) to reduce both specialty training positions and the length of training in these programs. General Surgery residencies often provide prerequisite training for surgery specialty training and will be affected by these changes. The purpose of this study is to identify the quality, outcome, and differences between PGYI-PGYIII categorical general surgery residents (GS) and matched prerequisite plastic surgery residents (PS). Concurrent comparisons analyzed American Board of Surgery Inservice Training Examinations (ABSITE) data from 1980-1992 as well as the surgery operative logs (SOL) and the curriculum of matched residents from 1989-1992. Outcome was assessed by board performance and from a piloted questionnaire to all PS graduates of the combined (3-year GS and 2-year PS) program. ABSITE analysis demonstrated satisfactory performance for both PS and GS at each PGY level, with significant increases each year for GS, but only between PGYI and PGYII for PS; there was a significant difference between PS and GS at all PGY levels. SOL analysis paralleled the curriculum and demonstrated more plastic surgery for PS compared to GS, with no difference in general surgery or hand surgery. PS program graduate respondents (32/44-72.7%) identified that the GS training/PS training was appropriate (71.9%/93.8%), effective (90.7%/93.8%) and of appropriate duration (87.5%/75.1%). 87.5 per cent of PS graduates completed ABPS certification. Combined PS training in all PS programs would reduce GME payments by over $20 million. Combined PS training is effective, appropriate, resource-efficient, and has an excellent outcome, but it requires a specific curriculum and close coordination between General Surgery and Plastic Surgery programs.

Attitude of Health Personnel↗

PubMed1994

Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF.

The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states.

Animals↗

PubMed1994

Dopaminergic terminals form synaptic contacts with enkephalinergic striatal neurons in pigeons: an electron microscopic study.

Medium spiny projection neurons of the striatum consist of two major neuropeptide-specific types, one type containing substance P and another type containing enkephalin. Both of these types have been shown to receive dopaminergic input onto their perikarya and proximal dendrites. However, whether each of these types receives direct dopaminergic input onto distal dendritic shafts and onto dendritic spines has not been explored in depth. In the present study, we used electron microscopic immunohistochemical double-label techniques to examine the synaptic organization of dopaminergic input onto enkephalin-positive (ENK+) striatal neurons in pigeons, in whom ENK+ striatal perikarya, dendritic shafts and spines can be readily labeled. Antibodies against tyrosine hydroxylase were used to label dopaminergic terminals using a silver-intensified immunogold method. ENK+ neurons were labeled using diaminobenzidine. We found that dopaminergic terminals make appositions and form symmetric synapses with the perikarya, dendritic shafts, and dendritic spine necks of ENK+ striatal neurons. Thus, nigral dopaminergic neurons provide a monosynaptic input onto ENK+ striatal neurons in a manner similar to that described previously by us for substance P-positive striatal medium spiny neurons.

Animals↗