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Biomedical subjects

W G Tatton

Publications and source records attributed to W G Tatton.

83 records · Page 5Linked to original sources
PubMed1975

Motor responses to sudden limb displacements in primates with specific CNS lesions and in human patients with motor system disorders.

Central feedback pathways for motor control were studied by recording EMG responses to sudden upper limb displacements in humans and monkeys using a precision torque motor to generate step load changes. Normal human subjects showed three short-latency EMG responses (M1, M2 and M3) which appear to correspond to those recorded from trained monkeys. The M2 and M3 components, thought to represent feedback in supraspinal pathways, were significantly increased when the subjects were instructed to actively compensate for the load changes. Parkinsonian patients with rigidity showed evidence of markedly increased feedback over the interval for the M2 and M3 responses and appeared to have lost the ability to modulate feedback according to the motor task being performed. The results are discussed with reference to recent research on motor control mechanisms in primates and a tentative model for the basis of Parkinsonian rigidity is proposed.

Animals↗
PubMed1975

Analysis of postural motoneuron activity in crayfish abdomen. I. Coordination by premotoneuron connections.

The activity of the crayfish abdominal postural motoneurons and their associated neurons (the accessory neuron(s) and the MRO(1)) were examined with the aid of techniques for the analysis of simultaneously recorded spike trains. A means of reliably identifying the spikes of the individual motoneurons based on their relative axon conduction velocities is presented. The analyses show that: 1) the large, phasically active synergist motoneurons innervating muscles producing the same movement show a marked similarity in their average responses, which is independent of the input source; 2) the small, tonically active and the middle-sized, tonicphasic synergist motoneurons innervating the same muscle and similar synergist motoneurons innervating antagonistic muscles are coordinated entirely by premotoneuron connections; 3) the accessory neuron is coordinated in its activity with the phasically active flexor excitor motoneurons and the extensor inhibitor motoneuron and thereby functions as a flexor synergist; and 4) the simultaneous presentation of flexion-producing and extension-producing inputs to the postural system results in a reciprocal oscillation in flexor-extensor motoneuron output. The functional significance of these results with respect to the operation of the postural system are discussed.

Abdominal Muscles↗
PubMed1975

Analysis of postural motoneuron activity in crayfish abdomen. II. Coordination by excitatory and inhibitory connections between motoneurons.

The identified spike trains of the crayfish abdominal postural efferent neurons were recorded simultaneously from one or more segments. The efferent activity was analyzed using cross-correlation histograms, peristimulus time scatter diagrams, and specialized antidromic techniques. The analyses show that the larger, phasically active motoneurons are coordinated in their activity by cross connections made at the motoneuron level. The cross connections are both excitatory and inhibitor in nature and result in significant alterations in spike output. Further, the accessory neuron receives an inhibitory cross connection from a middle-sized extensor excitor motoneuron or motoneurons. In each case, the cross connections appear to be appropriate to the function of the postural system.

Abdominal Muscles↗
PubMedDate not supplied

Different rates of age-related loss for four murine monoaminergic neuronal populations.

The age-related loss of locus coeruleus (LC) noradrenergic neurons, substantia nigra compacta (SNc) dopaminergic neurons, dopaminergic retinal amacrine (rAm) neurons and raphe serotonergic neurons, identified using antibodies against tyrosine hydroxylase (TH) and serotonin (5HT) was investigated in C57B1 mice aged 8 to 104 weeks. The neuronal somata were counted and their locations three-dimensionally reconstructed from serial sections alternately immunoreacted or Nissl stained. Nonlinear estimation analysis showed that decaying exponential equations best fitted the plots of neuronal numbers versus age and each subtype was lost according to different exponential constants of -0.015, -0.013, -0.004 and -0.001 for LC TH+, SNc TH+, rAm TH+ and raphe 5HT+ neurons, respectively. Neurons were lost from all different subregions within the nuclei or the retinae. Counts of immediately adjacent TH-immunoreacted and Nissl-stained sections through the LC at different ages indicate that the neuronal loss was due to neuronal death rather than loss of TH immunoreactivity. The markedly different rates of age-related neuronal loss for the four monoaminergic subtypes offer a model to study the underlying molecular and cellular mechanisms.

Aging↗
PubMedDate not supplied

Increased dopamine synthesis in aging substantia nigra neurons.

Striatal dopamine (DA) and metabolite (DOPAC) levels in 8-, 21-, 52- and 104-week-old C57BL mice were compared with those in 11-week-old mice, 20 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. DA and DOPAC concentrations expressed relative to striatal wet weight did not change with age. In contrast, DA and DOPAC levels increased almost linearly when values were expressed relative to the proportion of remaining tyrosine hydroxylase-positive (TH+) SNc neurons, reaching a 5-7-fold increase per average remaining TH+ neuron by 104 weeks of age (corresponding to neuronal loss of 70%) relative to that found per average neuron in 8-week-old mice. DA and DOPAC levels per average remaining TH+ SNc neuron following MPTP increased for low doses (neuronal losses less than 42%) but decreased for higher doses (55 and 70% losses) but the DOPAC/DA ratio per SNc neuron increased and was 9-fold higher in the 300 mg/kg MPTP-treated animals in comparison to saline controls. Cytoplasmic TH protein (estimated by somal TH immunodensity) was increased by 45% in SNc somata from mice treated with 150 mg/kg MPTP in comparison to saline controls, and by 63% in 104-week-old mice in comparison to 8-week-old animals. This study provides evidence that an average surviving TH+ SNc neuron compensates for the age-related loss of other SNc neurons by increasing dopamine synthesis similar to younger SNc neurons surviving low levels of toxically induced damage and that the compensation may be in part mediated by increased synthesis of TH.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Mitochondrial membrane potential in aging cells.

Decreased mitochondrial membrane potential (DeltaPsi(M)) has been found in a variety of aging cell types from several mammalian species. The physiological significance and mechanisms of the decreased DeltaPsi(M) in aging are not well understood. This review considers the generation of DeltaPsi(M) and its role in ATP generation together with factors that modify DeltaPsi(M) with emphasis on mitochondrial membrane permeability, particularly the role of a multiprotein membrane megapore, the mitochondrial permeability transition pore complex (PTPC). Previous data showing decreased DeltaPsi(M) in aged cells is considered in relation to the methods available to estimate DeltaPsi(M). In the past the majority of studies used whole cell rhodamine 123 fluorescence to estimate DeltaPsi(M) in lymphocytes from mice or rats. Imaging of DeltaPsi(M) in living, in situ mitochondria using laser confocal scanning microscopy offers advantages over whole cell measurements or those from isolated mitochondria, particularly if several different potentiometric dyes are employed. Furthermore, high resolution imaging of the newer fixable potentiometric dyes allows immunocytochemistry for specific proteins and DeltaPsi(M) to be examined in the same cells or even the same mitochondria. We found that decreased DeltaPsi(M) in p53 overexpression-induced or naturally occurring senescence is associated with decreased responsiveness of the PTPC to agents that induce either its opening or closing. The decreased PTPC responsiveness seems to reflect, at least in part, decreased levels of a key PTPC protein, the adenine nucleotide translocase. We also consider the possible basis for decreased DeltaPsi(M) in fibroblasts from patients with Parkinson's disease, an age-related neurodegenerative disease. Finally, we speculate on the mechanisms and functional significance of decreased DeltaPsi(M) in aging.

Aging↗
PubMedDate not supplied

Apoptotic mechanisms in neurodegeneration: possible relevance to glaucoma.

Deprenyl, a monoamine oxidase inhibitor used in the treatment of Parkinson's disease, along with its primary metabolite desmethyldeprenyl (DES) have been shown to reduce neuronal apoptosis by a mechanism that requires gene transcription and involves the maintenance of mitochondrial membrane potential. This review article explores the mechanisms by which DES maintains mitochondrial membrane potential. Mediated by GAPDH binding, DES increases mitochondrial BCL-2 and BCL-xL levels and decreases BAX levels thereby preventing the permeability transition pore (PTP) form opening and preventing apoptotic degradation. The favorable effects of deprenyl on neuronal apoptosis suggests the therapeutic potential of designing compounds with the capacity to alter the configurations of pro-apoptosis or anti-apoptotic proteins.

Animals↗
PubMedDate not supplied

Apoptosis and anti-apoptosis signalling in glaucomatous retinopathy.

PURPOSE: Recent studies in the post-mortem human retina have suggested that apoptosis contributes to retinal ganglion cell (RGC) loss in glaucoma. If apoptosis contributes significantly to glaucomatous RGC loss, and if the specific apoptosis signalling pathways for glaucomatous apoptosis can be determined, agents that interrupt or oppose the signalling have the potential to slow the progression of glaucoma. METHODS: Recent data in animal models indicate that mitochondrially-dependent apoptosis contributes to RGC loss in glaucoma. Mitochondrially-dependent apoptosis involves proteins like BAX that increase mitochondrial membrane permeability and promote apoptosis and proteins like BCL-2 that decrease mitochondrial membrane permeability and reduce apoptosis. New protein synthesis induced by the alpha-2 agonist, brimonidine, prevents decreases in the levels of BCL-2 and thereby reduces mitochondrially-dependent apoptosis. CONCLUSIONS: Brimonidine appears to maintain BCL-2 levels by supporting the activity of an intrinsic anti-apoptosis signalling system that involves phosphorylation of protein kinase B. Phosphorylated protein kinase B appears to counteract the apoptosis signalling mechanisms which operate in glaucomatous retina.

Adrenergic alpha-Agonists↗