Biomedical subjects

H F Baker

Publications and source records attributed to H F Baker.

At least 37 records · Page 2Linked to original sources

PubMed1999

Unrearable litters and prenatal reduction of litter size in the common marmoset (Callithrix jacchus).

It is widely believed that common marmosets (Callithrx jacchus) typically give birth to twins under natural conditions. In captivity, however, births of triplets or even larger litters are common, although parents rarely succeed in rearing more than two offspring. The traditional interpretation is that captive conditions, notably the ready availability of food, have led to increased reproductive output, perhaps involving a higher ovulation rate. The present paper provides evidence, combined from ultrasound examinations between ovulation and birth and hysterotomies conducted during the late embryonic and early fetal phase, that the litter size can be progressively reduced during pregnancy without spontaneous abortion. There is an unusually long lag phase prior to the onset of embryonic growth in common marmosets; the fetal stage does not begin until day 80 of the 144-day pregnancy. Reduction in litter size occurs during embryonic stages (up to day 80), and continues into the fetal stages. These results indicate that the common marmoset is adapted for flexible modification of litter size between ovulation and birth. The high incidence of triplet births in captive colonies may therefore be an expression of an adapted natural developmental process under artificial circumstances.

Abortion, Veterinary↗

PubMed1998

The role of the central cholinergic projections in cognition: implications of the effects of scopolamine on discrimination learning by monkeys.

In humans, administration of the cholinergic antagonist scopolamine impairs the encoding of information into long-term memory and has effects on other cognitive processes. It has been supposed that it is inhibition of the rising cholinergic projections from the basal forebrain, specifically from the basal nucleus of Meynert (NBM) to the neocortex and from the medial septum/vertical limb of the diagonal band of Broca (MS/VDB) to the hippocampus, that results in these cognitive impairments. In this paper, we describe the effects of scopolamine treatment in monkeys on learning different sorts of visual discrimination and visuospatial conditional tasks and compare these results to the effects of lesions of the rising cholinergic projections. Experiments in rodents in which these projections have been selectively destroyed have failed to produce a consensus view of the functions of these two areas. In particular, highly specific immunotoxic lesions of the NBM have largely failed to produce changes in task performance that can be interpreted as resulting from a cognitive impairment. In monkeys, lesions of the NBM produce modest or short-lasting, impairments in visual discrimination learning, retention, and reversal, whereas lesions of the MS/VDB produce large and permanent impairments of certain types of conditional learning. Similar impairments produced by scopolamine in monkeys and additive effects of lesions of the NBM or MS/VDB with scopolamine suggest that scopolamine has these effects by acting on the rising cholinergic pathways rather than on other cholinergic systems in the brain. It is argued that the rising cholinergic projections sustain the functions of the target areas; in the case of the hippocampus in humans, the function is usually regarded as being the analysis of information in a way that is pertinent to the formation of episodic memories and in the case of the neocortex, is the analysis of information in a manner that is relevant to the cognitive processing of on-going events and the acquisition of semantic knowledge.

Acetylcholine↗

PubMed1998

Functional integration of striatal allografts in a primate model of Huntington's disease.

Huntington's disease is an autosomal dominant, inherited disorder that results in progressive degeneration of the basal ganglia (especially the neostriatal caudate nucleus and putamen) and other forebrain structures and is associated with a clinical profile of movement, cognitive and psychiatric impairments for which there is at present no effective therapy. Neuropathological, neurochemical and behavioral features of the disease can all be reproduced in experimental animals by local injection of excitotoxic or metabolic toxins into the neostriatum. All these features of the disease can be alleviated, at least in rats, by transplantation of embryonic striatal tissue into the degenerated striatum, which was the basis for commencing the first clinical trials of striatal transplantation in Huntington's patients. However, although rat striatal xenografts may temporarily reduce apomorphine-induced dyskinesias in monkeys, there has been no demonstration that allograft techniques that work well in rats translate effectively to the much larger differentiated striatum of primates. Here we demonstrate good survival, differentiation and integration of striatal allografts in the primate neostriatum, and recovery in a test of skilled motor performance. Long-term graft survival in primates indicates probable success for clinical transplants in Huntington's disease; in addition, our data suggest that graft placement has a direct influence on the pattern and extent of functional recovery.

Animals↗

PubMed1998

Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy.

Prion protein (PrP) immunohistochemical staining of the brains of common marmosets (Callithrix jacchus) with experimental transmissible spongiform encephalopathy is described. The monkeys (n = 17) had been injected, intracerebrally, 17-49 months previously with homogenates of brain tissue taken post mortem from a cow with BSE (n = 2 monkeys), a sheep with natural scrapie (n = 2 monkeys), human cases of growth hormone related Creutzfeldt-Jakob disease (CJD) (n = 2 monkeys), sporadic CJD (n = 5 monkeys), or Gerstmann-Sträussler-Scheinker disease (GSS) (n = 4 monkeys), or from monkeys with spongiform encephalopathy resulting from injection with brain tissue from these last two cases (n = 1 monkey from each case). Only diffuse PrP-staining was seen in monkeys injected with CJD-material whereas more aggregated deposits of PrP were seen in monkeys injected with BSE-, scrapie--and GSS-brain tissue. There were no patterns of staining specific to the brains injected with BSE-material that could be used to identify the origin of that inoculum. BSE--and scrapie-injected monkey brains could be distinguished from each other because in BSE-injected monkey brain the spongiform vacuolation was largely confined to subcortical structures whereas in scrapie-injected monkey brain the spongiform vacuolation was also prominent in the neocortex. The patterns of PrP deposition differed markedly between those seen in monkey brains injected with BSE-material or CJD-material, but the patterns of PrP staining seen in monkey brains injected with BSE-material were also seen in monkey brains injected with scrapie--or GSS-material. Overall there was a correlation between the length of the incubation period and the amount of aggregated PrP-staining, but no correlation between the neuropathological picture and the clinical presentation of neurological signs.

Adult↗

PubMed1997

Learning impairment induced by lesion of the CA1 field of the primate hippocampus: attempts to ameliorate the impairment by transplantation of fetal CA1 tissue.

Monkeys with bilateral excitotoxic lesion of the CA1 field of the hippocampus were severely impaired at learning visuospatial conditional tasks. This was not a general spatial impairment, because the animals were not impaired on serial spatial reversal, which requires response flexibility in the spatial domain; they were not impaired at learning to choose the position furthest away from a single stimulus, which requires analysis of spatial layout of the test area, and they were not impaired at discriminating between two patterns that differed only in orientation. CA1-lesioned monkeys were impaired at learning a visuospatial conditional task when trials of the two component types "if AA go left" and "if BB go right" were presented according to either a pseudorandom or alternating schedule; but they were not impaired if one component type of trial was presented until three consecutive correct responses were made, followed by the other type of trial, to three consecutive correct responses. In all cases testing continued until a criterion of 27 of 30 consecutive correct responses across both types of trial was achieved. Although this suggests that CA1-lesioned animals are particularly prone to interference effects, they had no difficulty in learning ten concurrent visual discriminations presented against either a uniform background or with each discrimination presented against its own distinctive background, a condition that might reduce interference in unoperated monkeys. Interference following hippocampal damage might occur at a deeper level than stimulus identification such that animals with hippocampal damage may be able to learn about many aspects of different stimuli in parallel but may be unable to learn about multiple related aspects of the same subject matter. Monkeys with grafts of fetal CA1 tissue in the lesioned CA1 field showed significant improvement relative to CA1-lesioned animals on those tasks on which CA1-lesioned animals were impaired, although they remained impaired relative to control animals. This suggests that the grafts had produced some improvement in performance. Grafted monkeys did not differ from unoperated control monkeys or from CA1-lesioned monkeys on those tasks that were not sensitive to CA1 damage. This demonstrates that the grafts did not have an additional deleterious effect on cognitive performance.

Animals↗

PubMed1997

Evidence for a specific information processing deficit in monkeys with lesions of the septo-hippocampal system.

Monkeys with dysfunction of the septo-hippocampal system induced by excitotoxic lesion of the CA1 region of the hippocampus, or the septal/diagonal band area (which sends cholinergic projections to the hippocampus via the fornix), or with fornix transection were impaired on conditional learning tasks (when X choose A not B, when Y choose B not A) when trials with these different contingencies were presented in pseudorandom order but they were not impaired on learning this type of task if, prior to learning with trials in the pseudorandom order, the two types of trial had been presented in a fixed number of alternating batches of each type of trial. These results suggest that the septo-hippocampal system is required to process information in a particular type of way rather than to process a particular type of information and supports the view that the amnesia which results from medial temporal lobe damage in humans comprises an impairment of encoding information into long-term memory.

Amnesia↗

PubMed1997

Learning impairments following injection of a selective cholinergic immunotoxin, ME20.4 IgG-saporin, into the basal nucleus of Meynert in monkeys.

Four groups of monkeys (Callithrix jacchus) were injected with saline or increasing amounts of the immunotoxin, ME20.4 IgG-saporin, directly into the basal nucleus of Meynert via a frontal trajectory which avoided damage to the overlying basal ganglia. ME20.4 IgG binds to the primate p75 low-affinity neurotrophin receptor, when the saporin derivitized antibody is injected into the basal forebrain, it selectively destroys the magnocellular neurons of the basal nucleus of Meynert which are the cells of origin of the cholinergic projection to the neocortex. The highest dose of ME20.4 IgG-saporin produced a significant impairment on acquisition of a perceptually difficult visual discrimination. There was no significant effect on retention of tasks learnt before or after surgery, nor on concurrent acquisition of several perceptually easy discriminations or serial reversal of an easy discrimination. These results suggest that the impairment is not due to visual, motor or motivational difficulties and does not consist of difficulties with the formation of reward associations. Rather the impairment is largely confined to acquisition of perceptual discriminations. There was a significant correlation between the density of ME20.4 immunostaining in the basal nucleus of Meynert and the density of acetylcholinesterase histochemical staining in the frontal and temporal cortex and an inverse correlation between both of these and the degree of learning impairment in the animals. Lesioned animals also showed significant impairment on acquisition and reversal of perceptually easy discriminations when treated with a dose of scopolamine which did not impair performance in control animals. These results provide further evidence that cortical cholinergic neurotransmission contributes to certain forms of learning. The availability of a selective cholinergic immunotoxin effective in primates provides an important new tool for the study of cholinergic function and its involvement in ageing, Alzheimer's disease and other pathological states.

Animals↗

PubMed1997

The distribution of p75 neurotrophin receptor-immunoreactive cells in the forebrain of the common marmoset (Callithrix jacchus).

The distribution of neurones that could be stained immunohistochemically with antibody to the p75 neurotrophin protein was studied in the forebrain of the common marmoset. The p75-immunoreactive forebrain cells appear to correspond to choline acetyltransferase-immunoreactive (i.e., cholinergic) neurones. Two populations of cells could be distinguished on the basis of the intensity of p75 immunostaining. Moderately stained cells correspond to cholinergic interneurones of the caudate and putamen, while intensely stained cells correspond to the cholinergic neurones projecting to the cortex, amygdala, and hippocampus, located in the septum, diagonal band, and basal nucleus of Meynert. The distribution of cells of the diagonal band/basal nucleus complex is more extensive in the marmoset than in other primate species, extending into parts of the postcommissural fornix via the posterior septum, and by small projections dorsal to the anterior commissure and via the thalamic fasciculus from the basal nucleus; the posterior extent of the basal nucleus continues extensively into the lamina between the globus pallidus and the putamen.

Animals↗

PubMed1997

The nature of transmission in prion diseases.

Replicating biological information is usually stored only within nucleic acid. The existence of 'strains' of agent in prion disease (scrapie, BSE, CJD) has been taken to indicate an independent genome within the transmissible agent. Other replicable information exists, however, both in biology and elsewhere, including, for example, the 'meme' (the neutral correlate of ideas which replicate in human brains by communication) and the computer virus. From this broader viewpoint, we explore the possibility that 'strain' differences in prion disease reflect biological information stored within the prion protein rather than in nucleic acid. Much of the disease variation in mice (used as evidence for strain differences) can be accounted for by the primary structures of the prion protein of the host (the experimentally infected mouse) and the donor mouse (from which infectious tissue is taken). Information determining residual disease variation (when these factors have been excluded) may reside in different conformational states of host prion protein. Prion protein can adopt different conformational and glycosylation states. The information which these states contain is only partially conserved on transmission between animals, permitting the appearances of both 'strain stability' and 'strain mutation'. Different sources of replicating, biological information including information in the 'agent' (the abnormal form of prion protein) and in the host prion gene (PRNP) are in evolutionary competition. We argue that, in the prion diseases, replicating information is not carried in nucleic acid in either the host or the 'agent' but is carried within the conformational state of the abnormal form of prion protein.

Animals↗

PubMed1996