Search PubMed⌕ Search

Biomedical subjects

R G Mair

Publications and source records attributed to R G Mair.

At least 37 records · Page 2Linked to original sources
PubMed1991

Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency.

Rats that had recovered from pyrithiamine-induced thiamine deficiency (PTD) were compared with controls for spatial, auditory, and olfactory serial reversal learning (SRL); spatial matching to sample (MTS); auditory go-no-go discrimination; and open-field exploration. PTD rats made more errors reaching criterion for SRL in all modalities but showed normal transfer effects between problems. PTD rats were also impaired in learning the go-no-go and MTS tasks and showed consistent alterations in exploratory activity. It is argued that the PTD rat, like human Korsakoff patients, have impairments of learning and memory (but spared capacity for reference memory) that extend across sensory modalities. Postmortem analyses showed normal indices of cortical cholinergic, noradrenergic, dopaminergic, and serotonergic function and consistent bilateral lesions of the thalamus, which were centered on the internal medullary lamina, and the medial mammillary nucleus.

Animals↗
PubMed1991

Response latency and accuracy on a pretrained nonmatching-to-sample task in rats recovered from pyrithiamine-induced thiamine deficiency.

Rats were trained for 1,345 spatial nonmatching-to-sample (NMTS) trials, matched, assigned to pyrithiamine-induced thiamine deficiency (PTD) or control treatments, recovered, and re-tested for 400 trials of NMTS. The PTD model produced two bilaterally symmetrical lesions: one of medial thalamus that was centered on the internal medullary lamina (IML) and another involving the mammillary bodies. PTD rats with complete IML lesions showed a sharp drop in performance that persisted throughout posttreatment training. PTD rats with IML sparing were impaired immediately after treatment but improved to a level comparable to that of controls. For all animals, NMTS accuracy decreased for longer latency responses. PTD animals differed from controls primarily in the low frequency and inaccuracy of their short-latency (0-2.9 s) responses. The improvement of the PTD rats with IML sparing was marked by an increase in both the number and accuracy of short-latency responses.

Animals↗
PubMed1990

The Korsakoff syndrome: a neurochemical perspective.

Korsakoff's disease is an amnesic syndrome associated with midline diencephalic and brain stem pathology. A number of neurochemical systems course through or near the loci of brain lesions found postmortem in Korsakoff patients, which has stimulated studies to learn whether these systems are implicated in amnesia. Data suggest that the loss of brain catecholamine function contributes to this amnesic syndrome and may also be a factor in the memory impairments associated with normal aging. At present, data are insufficient to determine whether cholinergic systems are disturbed in Korsakoff's patients; however, it is likely that multiple neurochemical abnormalities underlie this disorder.

Alcohol Amnestic Disorder↗
PubMed1990

Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain.

An acute bout of pyrithiamine-induced thiamine deficiency (PTD) produces pathologic lesions within thalamus, mammillary body, and periventricular regions of rat brain. The biological bases for these pathologic changes and their selective distribution within the brain are unclear. The type of tissue damage observed within the thalamus of PTD rats closely resembles that observed following anoxic-ischemic insults and suggests the involvement of excitotoxic amino acids in its pathogenesis. The effects of the N-methyl-D-aspartate receptor antagonist MK-801 (3 mg/kg, i. p.) on brain lesions and amino acid changes have been assessed in rats killed during the late acute stages of PTD. A marked loss of neurons within midline intralaminar nuclei and the posterior nuclear group of the thalamus were observed in the early acute stage of PTD treatment. In the late acute stage, these changes were present throughout the entire thalamus and extended caudally to the periacqueductal gray and mesencephalic tegmentum. Hemorrhagic lesions were observed only in the late acute group and were the primary lesion within the mammillary body and medial and lateral geniculates. No pathologic changes were observed in hippocampus, amygdala, and cortex. MK-801 administered during the late stages resulted in a marked attenuation of necrotic damage to thalamus and periacqueductal gray and a reduction in the number and size of hemorrhagic lesions. Significant reductions of aspartate and glutamate and increases of glycine were observed in 5 regions of thalamus, the hippocampus, hypothalamus, and mammillary bodies of both the early and late acute PTD groups. Levels of GABA and taurine in caudal areas were significantly elevated in the early acute stage but were unchanged from controls in the late acute group. These amino acid changes were reduced in the MK-801 treated late acute group. These observations suggest that NMDA receptors are involved the pathogenesis of PTD-induced brain lesions and that nuclei of the intralaminar and posterior nuclear groups are most vulnerable to PTD effects.

Amino Acids↗
PubMed1988

Memory effect of DL-threo-3,4-dihydroxyphenylserine (DOPS) in human Korsakoff's disease.

A group of amnesic patients with Korsakoff's disease were treated with a single 1 g dose of DL-threo-3,4-dihydroxyphenylserine (DOPS) and placebo (lactose) in a double-blind crossover study. Three hours following administration, patients were given a battery of psychometric tests to determine the effects of the treatment on memory functions. Administration of DOPS had a significant effect on performance on the Memory Passages test but not on any of the other measures of memory. The effect of DOPS on Memory Passages is similar to the response observed following administration of clonidine in Korsakoff patients. Blood pressure and pulse, measured before and every 2 h after treatment, were unaffected by DOPS.

Alcohol Amnestic Disorder↗
PubMed1988

Long-lasting changes in regional brain amino acids and monoamines in recovered pyrithiamine treated rats.

Rats were subjected to a severe bout of thiamine deficiency induced by daily pyrithiamine + a thiamine deficient diet, reversed by thiamine administration and allowed to recover. Pyrithiamine treated animals demonstrated impaired retention of a 24 h recall of passive avoidance. Regional brain concentration of norepinephrine, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, GABA, glutamate, aspartate, glutamine, and glycine were determined after 2 and 9 weeks of nutritional recovery. A significant increase in NE content of cerebellum from the pyrithiamine treated animals was observed at both 2 and 9 week recovery periods. The concentrations of serotonin and its metabolite were significantly elevated in midbrain-thalamus and striatum. Significant reductions of GABA and glutamate were also observed in midbrain-thalamus. Amino acid levels in all other brain areas were unchanged from pair-fed controls. These results suggest regionally specific, chronic alterations in GABA, glutamate, serotonin, and norepinephrine activity following recovery from an acute bout of pyrithiamine-induced thiamine deficiency. The absence of a permanent reduction of cortical norepinephrine similar to that observed in an earlier study is discussed.

Amino Acids↗
PubMed1988

Behavioral impairments, brain lesions and monoaminergic activity in the rat following recovery from a bout of thiamine deficiency.

Learning impairments were measured in rats following recovery from a subacute bout of thiamine deficiency. Behavioral training was carried out in an automated T-maze, beginning with paired run spatial delayed non-matching to sample (PR-1), then light-dark discrimination (LD), light-dark discrimination reversal (LD-R), spatial discrimination (SD), spatial discrimination-reversal (SD-R), and finally retraining on the original paired run task (PR-2). Comparable deficits were observed for PR-1 and PR-2, thus demonstrating long-lasting impairment on delayed non-matching to sample. Experimentals performed as well as controls on LD and LD-R. Two experimental animals were unable to perform above chance on the simple SD task. The remaining 15 experimental animals were equivalent to controls on several measures of SD and SD-R performance (errors to criterion, number of animals reaching criterion, correct responses in last 60 trials) although they were significantly worse than controls on both PR-1 and PR-2. Taken together, these results indicate an impairment of representational memory (PR-1, PR-2) with a spared capacity for dispositional memory (LD, LD-R, SD, SD-R) as defined by Thomas and Spafford (Behav. Neurosci., 1984, 98: 394-404). Histological analyses of left hemispheres revealed a high incidence (94%) of thalamic lesions, specifically within the intralaminar nuclei and ventral parts of the mediodorsal nucleus; and an absence of detectable changes in other structures, including the mammillary bodies, hippocampus, cortex, and locus coeruleus. In the right hemispheres, assays of monoamines and metabolites in 17 brain regions showed significant reduction only for norepinephrine in entorhinal cortex. All animals that were selectively impaired on the paired-run task had both the medial thalamic lesions and reduction in entorhinal norepinephrine.

Alcohol Amnestic Disorder↗
PubMed1987

Monoamines and metabolites in cortex and subcortical structures: normal regional distribution and the effects of thiamine deficiency in the rat.

The present study measured the concentration of monoamines, metabolites and estimates of turnover rate in eighteen separate brain regions from controls and a rat model of Korsakoff's disease induced by a two week bout of pyrithiamine and thiamine deficient diet (PTD). A behaviorally tested control (n = 12) and PTD (n = 17) group, and a non-behaviorally tested PTD group (n = 8) were sacrificed 7 months after recovery from treatment. The brains were dissected into nine cortical areas and nine subcortical regions. In behaviorally tested PTD animals, a significant reduction of NE was observed in entorhinal cortex. Diminished norepinephrine (NE) concentration was also observed in entorhinal, hippocampal, septal and olfactory areas of the non-behaviorally tested PTD group. Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased in several brain areas, particularly midbrain-thalamus, striatum, of both groups of recovered PTD animals. These findings are discussed with respect to results and hypotheses presented in our previous study of this animal model. Significant differences in monoamine, metabolite and turnover estimates were also observed among cortical areas of the control animals. Entorhinal cortex contained the highest concentration of NE and 5-hydroxytryptamine (5-HT), while DA was highest in somatosensory cortex. The distribution of 5-HT and 5-HIAA were more homogeneous and displayed a rostral-caudal decline in concentration.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Reduced concentrations of arginine vasopressin and MHPG in lumbar CSF of patients with Korsakoff's psychosis.

The concentrations of arginine vasopressin (AVP), somatostatin (SS), and the primary brain metabolites of norepinephrine (MHPG), serotonin (5-HIAA), and dopamine (HVA) were measured in samples of lumbar CSF obtained from ten amnesics with Korsakoff's psychosis, four patients with a history of Korsakoff's psychosis who had recovered from the amnesic symptoms of this disease, and control subjects. Significant deficits were observed in the amnesic group for AVP and MHPG, but not for the other substances measured. Subjects who had recovered from the amnesic symptoms of Korsakoff's psychosis had increased concentrations of AVP and MHPG, but not of SS or the other monoamine metabolites.

Adult↗
PubMed1986

Cognitive enhancement in Korsakoff's psychosis by clonidine: a comparison with L-dopa and ephedrine.

Each of three catecholamine agonist medications (clonidine, L-dopa, and ephedrine) and placebo were administered for 2-week trials to a group of amnesics with Korsakoff's psychosis following a double-blind, counterbalanced design. During the last 3 days of each treatment, patients were given a battery of neuropsychological tests to determine the effects of the drugs on memory and related cognitive processes. Only clonidine had a significant effect on measures of anterograde amnesia, and this response was restricted to the same psychometric measures that improved with clonidine in an earlier study (McEntee and Mair 1980). Each of the medications affected performance on some measures of attention. None of the treatments had any effect on measures of retrograde amnesia or digit-symbol substitution. There appears to be a significant negative correlation between the amnestic effects of clonidine and the concentration of the primary noradrenergic metabolite in lumbar CSF (as measured prior to the initial drug trial).

Alcohol Amnestic Disorder↗
PubMed1986

Multimodal sensory discrimination deficits in Korsakoff's psychosis.

A consistent impairment in odor identification was observed among a group of 21 amnesic patients, diagnosed as having Korsakoff's psychosis. In a subsequent study of eight Korsakoff and matched alcoholic control subjects, a comparable olfactory deficit was again demonstrated, as well as impairment in color discrimination and auditory perception. No such deficit was observed for a picture identification task designed to control for the non-sensory demands of the olfactory test. Stepwise multiple regression analysis showed a significant correlation between odor identification scores and the concentration of the primary metabolite of norepinephrine in lumbar cerebrospinal fluid. The data demonstrate a consistent coincidence between memory impairment and deficient sensory perception among patients with Korsakoff's psychosis.

Adult↗
PubMed1986

Learning impairments after 6-OHDA treatment: a comparison with the effects of thiamine deficiency.

Cortical norepinephrine, dopamine and 3,4-dihydroxyphenylacetic acid were reduced by injection of 6-hydroxydopamine (6-OHDA) jointly into the cisterna magna and the dorsal noradrenergic bundle. On subsequent behavioral testing, deficits were observed for spatial delayed alternation learning, but not for active or passive avoidance. Treatment with clonidine resulted in a significant improvement in spatial delayed alteration for experimental as compared to control animals. Injections of 6-OHDA into the cisterna magna alone had no significant effect on brain chemistry or behavioral measures. These results are similar to previous observations following a bout of thiamine deficiency, in which cortical catecholamines were depleted in animals that had exhibited deficits for spatial delayed alternation learning. We argue that the cortical catecholamine deficits observed in post-thiamine-deficient animals are sufficient to account for the delayed alternation deficits observed in this animal model of Korsakoff's psychosis.

Alcohol Amnestic Disorder↗
PubMed1985

Thiamine deficiency depletes cortical norepinephrine and impairs learning processes in the rat.

Several lines of evidence indicate that thiamine deficiency causes the Wernicke-Korsakoff syndrome, a human memory disorder. The present study examined behavioral deficits in rats after recovery from a bout of thiamine deficiency. Following behavioral testing, the brains were dissected into regions and assayed biochemically for levels of dopamine, norepinephrine, serotonin and the primary metabolites of these monoamines. Based on previous findings in this laboratory, we predicted that thiamine deficiency not only produces behavioral deficits but loss in catecholamines as well. Impairments were observed for a spatial delayed alternation task that had been learned prior to experimental treatment. In addition, experimental animals were impaired in their ability to acquire two novel tasks, active and passive shock avoidance, after recovery from the acute effects of thiamine deficiency. Comparable deficits were not observed for a number of reflex responses that were measured to assess the general neurological state of the animals. Biochemical analyses revealed that the concentration of norepinephrine was reduced significantly in cortex-hippocampus and olfactory bulb but not in other regions, while dopamine and serotonin levels were not altered in any brain region examined. These data demonstrate that a bout of thiamine deficiency can produce persistent deficits in brain norepinephrine and concomitant decrements in behavioral measures of learning and memory. These results are consistent with our hypothesis and evidence that noradrenergic deficits contribute to the amnesic symptoms of Korsakoff's psychosis.

Alcohol Amnestic Disorder↗
PubMed1985

Monoamine activity correlates with psychometric deficits in Korsakoff's disease.

Korsakoff's psychosis is associated with impairments of memory and perception but not global dementia. We have previously reported diminished concentrations of catecholamine metabolites in the CSF of patients with Korsakoff's psychosis. In this study, we compared CSF monoamine metabolite data with performance on psychometric tests for 26 patients with this disease. We report that patients with more severe neurobehavioral deficits have lower concentrations of monoamine metabolites. Our data also provide evidence that diminished brain noradrenergic and dopaminergic activities are related to impairments on different psychometric tasks.

Alcohol Amnestic Disorder↗
PubMed1984

Transduction physiology of olfactory receptor cilia.

Electro-olfactograms (EOGs) evoked by 8 odorants from frog olfactory epithelia during ciliary regrowth and during epithelial regeneration were analyzed. During ciliary regrowth following detergent-induced ciliary removal, EOG amplitudes initially increase proportionately with ciliary length. EOGs reach maximal amplitudes after 2 days of growth, when cilia are 40 micron long. Therefore olfactory transduction sites are located primarily on cilia rather than on the dendrite terminal and most of the receptor current enters through the proximal portion of the cilium. Zinc sulfate lavage of the nasal cavity causes selective necrosis of the receptor epithelium. During epithelial regeneration, EOGs increase linearly with time from 13 days after zinc lavage, the time of first cilium emergence, through 30 days. The rate of increase is different for different odorants. At 30 days and within a period of a few days, EOG amplitudes increase abruptly, then asymptote. Thus the development of receptors for different substances occurs at different rates and occurs in two steps. The transition between the two developmental states is coincident with arrival of receptor axon terminals at the central nervous system and with the immobilization of the ciliary contractile apparatus. Since there is continual generation of new receptor neurons throughout life, EOGs recorded in a normal nose reflect a complex combination of the differing receptor processes of cells of differing developmental stages.

Animals↗