Journal of Neural Transmission

The concept of isoreceptors offers a possible clue to account for pharmacological and biochemical heterogeneity in specific receptor systems. The existence of isozymes has set the foundation for the definition of isoreceptors. The resulting criteria are applied to two central receptor complexes. Accordingly, the nicotinic acetylcholine receptor is defined as an isoreceptor, and research results on the GABA/benzodiazepine receptor are interpreted under the consideration of the possible existence of isoreceptors.

Studies suggest that frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is heterogeneous with division into four or five subtypes. To determine the degree of heterogeneity and the validity of the subtypes, we studied neuropathological variation within the frontal and temporal lobes of 94 cases of FTLD-TDP using quantitative estimates of density and principal components analysis (PCA). A PCA based on the density of TDP-43 immunoreactive neuronal cytoplasmic inclusions, oligodendroglial inclusions, neuronal intranuclear inclusions, and dystrophic neurites, surviving neurons, enlarged neurons, and vacuolation suggested that cases were not segregated into distinct subtypes. Variation in the density of the vacuoles was the greatest source of variation between cases. A PCA based on TDP-43 pathology alone suggested that cases of FTLD-TDP with progranulin (GRN) mutation segregated to some degree. The pathological phenotype of all four subtypes overlapped but subtypes 1 and 4 were the most distinctive. Cases with coexisting motor neuron disease (MND) or hippocampal sclerosis (HS) also appeared to segregate to some extent. We suggest: (1) pathological variation in FTLD-TDP is best described as a ‘continuum’ without clearly distinct subtypes, (2) vacuolation was the single greatest source of variation and reflects the ‘stage’ of the disease, and (3) within the FTLD-TDP ‘continuum’ cases with GRN mutation and with coexisting MND or HS may have a more distinctive pathology.

Two of the main biochemical features characteristic for oncogenic RNA (oncorna) viruses have been detected in human glioblastoma. In all tumors tested so far a RNA instructed DNA polymerase (“reverse transcriptase”) activity was present which exhibited the criteria specific for oncorna viruses. It was stimulable by the synthetic polynucleotide poly-rA: oligo-dT, it was almost insensitive to actinomycin D but very sensitive to ethidiumbromide. Using the simultaneous detection test, a high molecular weight RNA species was found in the subcellular fraction with the highest reverse transcriptase activity. As revealed by electron microscopy, this subcellular fraction contains particles of a morphology similar to oncogenic RNA viruses of the C-type.

Experiments on lightly anesthetized cats are described in which the autonomic reactivity, tested by the response of the hypothalamus to electrical stimulation, was altered reflexly by the lowering of the blood pressure (induced by acetylcholine, mecholyl or histamine) or by raising the blood pressure with noradrenaline or adrenaline. It was found: The quantitative differences in the degree of autonomic tuning produced by the different procedures are emphasized. The mechanism underlying the experimentally induced alterations in autonomic reactivity, the relation of these states of autonomic imbalance to homeostasis and their clinical and psychological significance are pointed out.

Sympathetic innervation to the melanophores of a siluroidParasilurus has been the sole instance of such innervation among lower vertebrates, in which the peripheral transmission to the effector cells is peculiarly cholinergic (Fujii andMiyashita, 1976). In an effort to find a similar case, we studied the nature of transmission to melanophores of a glass catfishKryptopterus. Electrical nervous stimulation brought about melanosome aggregation in the melanophores. While catecholamines were found ineffective, acetylcholine and its analogues were potently active in aggregating pigment. Atropine or scopolamine interferred with the action of both nervous stimulation and acetylcholine. Physostigmine, on the other hand, augmented the cholinergic effects. The conclusion was that the transmission was cholinergic, being mediated by cholinoceptors of muscarinic type, as in the case ofParasilurus.

Slow gait is ubiquitous among older adults and predicts cognitive decline and progression to dementia. Age-related structural brain changes could be responsible for abnormal gait. The purpose of this study was to determine whether brain lateral ventricle volume, a measure of brain atrophy, was associated with gait velocity among older adults with mild cognitive impairment (MCI), while considering the effects of age and brain vascular burden. Twenty community-dwellers with MCI, free of hydrocephalus, aged 76 years (69/80) [median (25th/75th percentile)] (35 % female) from the ‘Gait and Brain Study’ were included in this analysis. Quantitative gait performance was measured while steady-state walking at self-selected pace with a 6-m electronic portable walkway (GAITRite). Brain ventricle volume was quantified using semi-automated software from three-dimensional T1-weighted magnetic resonance imaging. Age, white matter hyperintensity burden and Mini-Mental State Examination score were used as potential confounders. Median gait velocity was 118.7 cm/s (104.4/131.3). Median brain ventricle volume was 39.9 mL (30.0/46.6) with the left ventricle being slightly larger than the right (P = 0.052). Brain ventricle volume was inversely associated with gait velocity (adjusted β = −0.63, P = 0.046). Volume of both the ventricular main bodies and the temporal horns correlated inversely with gait velocity (respectively, P = 0.009, P = 0.008). Left ventricle volume correlated with decreased gait velocity (P = 0.002) while right ventricle did not (P = 0.068). Slower gait velocity was associated with larger brain ventricle volume in our sample of people with MCI independent of age, cerebrovascular burden and cognitive worsening. This result may help elucidate the trajectories of cognitive and gait declines in people with MCI.