The aim of this project was to determine the neurotrophic factor survival requirements of PNS neurons during development and to clarify the role of certain receptors in mediating responsiveness. Members of the neurotrophin family of neurotrophic factors (NGF, BDNF, NT3 and NT4/5) and neurotrophic cytokines (CNTF, LIF, OSM, IL-6 and CT-1) were studied. The activity of a recently identified neurotrophin, NT4/5, was investigated in vitro. In cultures of mouse neurons, mammalian NT4/5 promoted the survival of the same kinds of neurons as BDNF and was as potent as BDNF, which is consistent with the action of both neurotrophins on the same receptor, TrkB. However, both mammalian NT-4/5 and the Xenopus homologue were less potent than mammalian BDNF on chicken embryo neurons, which is consistent with the lower evolutionary conservation of NT4/5. Interestingly, mammalian NT4/5 exhibited differences in potency on certain populations of chicken neurons that responded equally well to BDNF, and this may reflect differences in TrkB receptors in these different populations of neurons. To clarify the role of the common neurotrophin receptor in modulating the response of neurons to NGF, I then compared the actions of NGF with a mutated NGF protein that binds to TrkA, but does not bind to p75. At subsaturating concentrations, the NGF mutant was less effective than NGF in promoting the survival of embryonic sensory neurons and postnatal sympathetic neurons but was equally effective as NGF in promoting the survival of embryonic sympathetic neurons, indicating that binding of NGF to p75 enhances the sensitivity of NGF-dependent neurons to NGF at certain stages of development. To investigate if neurotrophic cytokines act on developing sensory neurons, I studied their effects in vitro. Whereas trigeminal neurons were responded to cytokines in the late fetal period, nodose neurons were supported by these factors throughout embryonic development. These findings indicate that different populations of PNS neurons display different patterns of responsiveness to neurotrophic cytokines during development.

BDNF binds to two transmembrane receptors: trkB, which is a tyrosine kinase essential for signalling, and p75, which is a common neurotrophin receptor whose role is contoversial. To determine the relationship between BDNF synthesis, BDNF receptor expression, and neuronal responsiveness, the expression of BDNF, trkB, and p75 mRNAs were studied for different populations of sensory neurons whose axons reach their targets and become dependent on BDNF for survival at different times. BDNF mRNA was expressed in the peripheral and central targets of these neurons prior to the arrival of sensory axons. The onset of BDNF responsiveness was preceded by the expression of first p75 mRNA then trkB mRNA, and neurons that start responding to BDNF early were the first to express trkB mRNA. BDNF upregulated trkB mRNA expression just shortly before the onset of BDNF dependence. BDNF is expressed not only in sensory neuron targets but in some of these neurons themselves. To determine whether BDNF is synthesized in NGF-dependent or BDNF-dependent neurons, BDNF mRNA expression was studied in purified populations of cranial sensory neurons that depend on either NGF or BDNF for survival. During the period of neuronal death, BDNF mRNA expression was highest in NGF-dependent cutaneous sensory neurons, lower in BDNF-dependent cutaneous sensory neurons, and undetectable in BDNF-dependent proprioceptive neurons. In coculture, NGF-dependent neurons promoted the survival of BDNF-dependent neurons by the production and release of BDNF, implying a paracrine role for BDNF during the period of naturally occurring neuronal death. To determine if the level of p75 expression in sensory neurons is related to the particular neurotrophin they require for survival, p75 mRNA levels were measured in purified populations of cranial sensory neurons. No clear relationship between the level of p75 mRNA expression and neuron type was observed. Studies of the regulation of p75 mRNA expression in sympathetic neuroblasts revealed that retinoic acid increased and membrane depolarization using KCl decreased the levels of p75 mRNA.

No description available.

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Thesis (M.A.)--Kent State University, 2008. / Title from PDF t.p. (viewed Oct. 15, 2009). Advisor: Joel Hughes. Keywords: PTSD, autonomic nervous system, parasympathetic nervous system, heart rate variability. Includes bibliographical references (p. 45-57).

No description available.

No description available.

Parental problem drinking (PPD) is associated with various forms of child psychopathology, including hyperactivity, conduct disorder, delinquency, depression and anxiety. However, not all children share the same risk for developing adjustment problems in the context of PPD. In this study, we examined patterns of sympathetic and parasympathetic nervous system activity account for differential susceptibility to the adverse effects of PPD in middle childhood. We found that reciprocal SNS activation protects against child internalizing symptoms in the context of mother problem drinking. We also found consistent interactions between PNS and SNS in predicting child internalizing problems. Coinhibition is linked to more internalizing symptoms including anxiety and depression. This study provides further support for Autonomic Space Theory and demonstrates the importance of taking both PNS and SNS into account when studying physiological response to stress.

Disruptive behavior problems are among the most commonly occurring forms of childhood psychopathology and show considerable stability beginning in early childhood. Investigations of the biological underpinnings of behavior problems have revealed that the influences of the parasympathetic branch of the autonomic nervous system on cardiac functions are central to self-regulation. Parasympathetic regulation of heart rate is indexed via respiratory sinus arrhythmia (RSA). Suppression of RSA during challenging emotional and cognitive tasks is associated with better emotional and behavioral functioning in preschoolers. However, the relationship between RSA suppression and preschool social functioning is still unclear. Further, direct relationships between behavior problems and RSA reactivity within command-based play tasks (i.e., child instructed to build 3 towers) with parents and other adults have yet to be examined. The present study experimentally evaluated the relationship between child RSA reactivity and adult (mother vs. staff) commands requiring child compliance during command-based play tasks in children ages 3-8 with and without disruptive behavior disorders (N=43). Child RSA suppression in response to commands was examined as a predictor of child command compliance during experimental play tasks and of general child behavior problems, and was compared across command-based interactions with mothers versus staff. Less RSA suppression in the context of mothers’ play-based commands was associated with more severe behavioral problems (p=.046). In the context of staff play-based commands, more RSA suppression was associated with more severe behavior problems (p=.009), an effect that was significant only among boys (p<.000). Further, greater child RSA suppression predicted greater compliance with mother-given commands (p=.017), but was unrelated to compliance with staff-given commands. The relationship between child RSA suppression and compliance with mother-given commands was moderated by child age, such that the effect of RSA suppression on child compliance was stronger for younger children than older children. Findings suggest that RSA reactivity to social demands, and the functional association between RSA suppression and behavioral compliance, vary by social context (i.e., mother vs. other adult command-givers) and identify child factors (i.e., age, gender) that influence these associations. This work may inform efforts to identify a biomarker of early childhood behavior problems.

INTRODUÇÃO. O aumento da densidade de arritmia ventricular e a redução da variabilidade da freqüência cardíaca estão associados com risco de morte súbita e mortalidade total em insuficiência cardíaca. A inibição colinesterásica com brometo de piridostigmina (PIR) aumenta a variabilidade da freqüência de pessoas normais, porém seu efeito em pacientes com insuficiência cardíaca é desconhecido. OBJETIVOS. Testar a hipótese de que a administração a curto prazo de piridostigmina reduz a densidade de arritmia ventricular e aumenta a variabilidade da freqüência cardíaca em pacientes com insuficiência cardíaca. MÉTODOS. Pacientes com insuficiência cardíaca e em ritmo sinusal participaram de um estudo duplo-cego, cruzado, randomizado para placebo e piridostigmina (30mg VO de 8 em 8 horas por 2 dias). Monitorização eletrocardiográfica ambulatorial de 24 horas foi realizada para análise de arritmia e para avaliação dos índices do domínio do tempo da variabilidade da freqüência cardíaca. Pacientes foram separados em 2 grupos, de acordo com a densidade de arritmia ventricular. O grupo Arritmia (n = 11) incluiu pacientes com mais de 10 extrassístoles ventriculares por hora (ESV/h), e o grupo Variabilidade da Freqüêcia Cardíaca (n = 12) incluiu pacientes com um número de ESVs em 24 horas que não excedia 1 % do número total de intervalos RR. RESULTADOS. No grupo Arritmia, PIR resultou em uma redução de 65% no número de extrassístoles ventriculares (Placebo 266 + 56 ESV/h vs. PIR 173 + 49 ESV/h; p = 0,03). No grupo da Variabilidade da Freqüência Cardíaca, a administração de PIR resultou em um aumento do intervalo RR médio (Placebo 733 + 22 ms vs PIR 790 + 33 ms; p = 0,01), e nos índices do domínio do tempo da variabilidade da freqüência cardíaca PNN50 (Placebo 3 + 1,1 % vs PIR 6 + 1,6 %; p = 0,03) e RMSSD (Placebo 21 + 2 vs PIR 27 + 3; p = 0,008). CONCLUSÃO. Em pacientes com insuficiência cardíaca, PIR reduziu a densidade de arritmia ventricular e aumentou a VFC, provavelmente por seu efeito colinomimético. Estudos a longo prazo com PIR em insuficiência cardíaca devem ser realizados. / OBJECTIVE To test the hypothesis that short-term administration of pyridostigmine bromide (PYR) reduces ventricular arrhythmia density and increases heart rate variability in patients with congestive heart failure. BACKGROUND Increased ventricular arrhythmia density and reduced heart rate variability are associated with risk of sudden death and overall mortality in patients with heart failure. Cholinesterase inhibition with pyridostigmine bromide increases heart rate variability in normal subjects, but its effect in patients with heart failure is unknown. METHODS Patients with heart failure and in sinus rhythm participated in a double-blind, cross-over protocol, randomized for placebo and pyridostigmine (30 mg PO TID for 2 days). Twenty-four hour electrocardiographic recordings were performed for arrhythmia analysis and for the measurement of time domain indices of heart rate variability. Patients were separated in 2 groups, according to their ventricular arrhythmia density. The Arrhythmia Group (n = 11) included patients with more than 10 ventricular premature beats per hour (VPBs/h), and the Heart Rate Variability Group (n = 12) included patients with a number of VPBs in 24 hours not exceeding 1 % of the total number of RR intervals. RESULTS For the Arrhythmia Group, PYR resulted in 65 % reduction of ventricular ectopic activity (Placebo 266 ± 56 VPBs/h vs. PYR 173 ± 49 VPBs/h; P = 0.03). For the Heart Rate Variability Group, PYR administration resulted in an increment of mean RR interval (Placebo 733 ± 22 msec vs PYR 790 ± 33 msec; P = 0.01), and in the time domain indices of heart rate variability RMSSD (Placebo 21± 2 vs PYR 27 ± 3; P = 0.01) and PNN50 (Placebo 3 ± 1 % vs PYR .6 ± 2 %; P = 0.03). CONCLUSION In patients with heart failure, PYR reduced ventricular arrhythmia density and increased HRV, most likely due to its cholinomimetic effect. Long-term trials with PYR in heart failure should be conducted.