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M C McCulloch

Publications and source records attributed to M C McCulloch.

23 records · Page 2Linked to original sources

The distribution of alterations in energy metabolism in the rat brain produced by apomorphine.

The effects of the putative dopaminergic agonist, apomorphine (0.15-5 mg/kg, i.v.), on glucose utilization in 43 anatomically discrete regions of the rat brain have been examined by the quantitative autoradiographic 2-deoxyglucose technique. Apomorphine failed to alter the rates of glucose utilization in 25 of these regions (for example, primary auditory areas, regions of white matter, hippocampal areas, nucleus accumbens and caudal regions of the neocortex). Dose-dependent alterations in glucose utilization were observed following apomorphine administration in a number of regions known to contain dopaminergic receptors (viz: caudate nucleus, substantia nigra, amygdala, subthalamic nucleus and anterior cingulate cortex). Moreover, dose-dependent alterations in glucose utilization were produced by apomorphine in a number of regions thought to contain few specific dopaminergic receptors (e.g., cerebellar hemisphere and vermis, lamina VI of rostral neocortical areas, and ventral nucleus of the thalamus). The distribution of alterations in glucose utilization following apomorphine administration are considered to reflect the functional involvement of the region in the overall response to apomorphine, and not simply the topography of dopaminergic receptor mechanisms.

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Retina-dependent activation by apomorphine of metabolic activity in the superficial layer of the superior colliculus.

Studies of the effect of the dopamine agonist apomorphine on local cerebral glucose utilization by means of the carbon-14-labeled deoxyglucose method demonstrate a dose-dependent metabolic activation in the superficial layer of the superior colliculus in the rat. Apomorphine stimulated glucose utilization in a number of other cerebral structures, but only the effect in the superficial layer of the superior colliculus depended on an intact retinal input. This effect was present with the animal in the light or in the dark, but was abolished by enucleation, which left the effects in other cerebral structures unimpaired. Activation of the superificial layer of the superior colliculus appears, therefore, to be secondary to an action of apomorphine on dopaminergic systems within the retina.

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Specific distribution of metabolic alterations in cerebral cortex following apomorphine administration.

The topographic distribution of dopaminergic receptors in the cerebral cortex closely parallels that of the dopaminergic innervation. In the rat, dopaminergic axons which originate in the mesencephalon are confined to a few discrete regions of the neocortex--anterior cingulate cortex, entorhinal cortex, frontal cortex (particularly anteromedial and supragenual areas) and the transitional zone between the neocortex and the pyriform cortex. Moreover, biochemical examinations of processes generally considered to be indicative of dopaminergic neuro-transmission--neuronal uptake of labelled dopamine or dopamine-activation of adenylate cyclase activity--have confirmed a highly restricted locus of action of dopaminergic systems in the cerebral cortex. We describe here data obtained using the 2-deoxyglucose technique in conjunction with conventional neuropharmacological techniques, suggesting that the influence of dopaminergic systems on cortical function extends beyond the known confines of the mesocortical dopaminergic system.

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Feline dysautonomia (the Key-Gaskell syndrome): an ultra structural study of autonomic ganglia and nerves.

Recently a feline dysautonomia of unknown aetiology, the Key-Gaskell syndrome, has caused widespread morbidity in the UK. This report describes the ultrastructural appearances of the autonomic ganglia and axons of the sympathetic chain in this condition. Nuclei of affected neurones were eccentric and abnormally crenated. Nucleolar abnormalities such as increased electron density (due to loss of the intranucleolar vacuoles), nucleolar segregation and ring nucleoli were observed in a proportion of neurones. There was marked loss of ribosomes, both bound and unbound, and cisternae of the rough endoplasmic reticulum were distended with a floccular electron dense material. Numerous smooth-walled cisternae were also present and complex stacks of smooth semi-parallel membranes were observed, probably derived from the smooth endoplasmic reticulum or Golgi apparatus. No normal Golgi formations were seen. Frequent autophagic vacuoles and membranous dense bodies were present in some cells. Many unmyelinated fibres in the sympathetic chain were swollen and contained vesiculo-tubular profiles, disordered neurotubules and filaments and various degenerating membranous organelles. Myelinated fibres within the sympathetic chain were also degenerating. These studies indicate that the organelles involved with protein biosynthesis are severely affected by the disease.

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Progressive axonopathy: an inherited neuropathy of boxer dogs. 2. The nature and distribution of the pathological changes.

This report describes the neuropathology of progressive axonopathy (PA), an autosomal recessive inherited neuropathy of Boxer dogs, which affects CNS and PNS. The nerve roots contain numerous myelin bubbles and proximal paranodal axonal swellings containing vesicles, vesiculo-tubular profiles and disorganized neurofilaments. The myelin sheath overlying such swellings is often attenuated. As the disease develops there are progressive changes in the myelin sheath with thinning at paranodal and internodal locations, loss of myelin from lengths of axon and the formation of short internodes with disproportionately thin sheaths. The abnormalities show a very definite selectivity for nerve roots and proximal nerves. Conversely, the frequency of degeneration and regeneration is greater distally except in the cervical ventral roots which contain numerous regenerating clusters. In the CNS numerous axonal spheroids are found in the lateral and ventral columns of the spinal cord and in various brain stem nuclei, particularly the superior olives, accessory cuneate nuclei and lateral lemniscus and its nucleus. Axonal degeneration which occurs mainly in the cord shows no obvious tract or proximal/distal selectivity. The optic pathways are also involved, predominantly adjacent to the chiasma. The autonomic nervous system is affected and distal limb muscles show varying, but usually minor, degrees of neurogenic atrophy. The condition, which has no obvious direct parallel in human or veterinary medicine, shows gross disturbances of axon-glial inter-relationships in both CNS and PNS.

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