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H E Laird

Publications and source records attributed to H E Laird.

36 records · Page 2Linked to original sources
PubMed1986

Abnormalities in the central cholinergic transmitter system of the genetically epilepsy-prone rat.

Seizure-experienced Genetically Epilepsy-prone Rats (GEPRs) have increased acetylcholine content and choline acetyltransferase activity in the thalamus and striatum. These cholinergic differences are accompanied by a slight but statistically significant reduction in acetylcholinesterase activity in the midbrain. In addition, no abnormalities were found in the numbers of specific 3H-QNB binding sites in the striatum, hippocampus, inferior colliculi or cortex. Other work has shown no difference in muscarinic receptor function as measured by carbachol-stimulated inositol-1-phosphate formation. These data suggest a possible presynaptic defect in the striatal and thalamic cholinergic system which may play some role in the seizure-prone state of the GEPR. However, caution must be used in interpreting these cholinergic derangements since more recent findings show no differences in thalamic acetylcholine content in seizure-naive GEPRs. Thus, the original cholinergic abnormalities detected in the seizure-experienced GEPR may be an enduring response to seizure activity.

Acetylcholine↗
PubMed1986

Neuronal response abnormalities in the inferior colliculus of the genetically epilepsy-prone rat.

The genetically epilepsy-prone (GEP) rat is susceptible to seizure induction by acoustic stimuli. The inferior colliculus (IC) has been implicated as being critically important in audiogenic seizure susceptibility based on lesion, electrical stimulation, and focal implantation experiments. The current study determined that GEP rats were most susceptible to seizure induction by pure tone bursts at 100 dB at a frequency of 12 kHz. IC neurons in the GEP rat exhibited a significantly elevated incidence of a particular response pattern at 12 kHz and at characteristic frequency. This pattern consisted of a peak at the beginning and end of the stimulus (onset-offset response). This response pattern only occurred with high intensity stimuli approximating those which induce seizures and may represent an afterdischarge phenomenon. The response threshold was significantly elevated and tuning characteristics were also significantly altered in IC neurons of GEP rats as compared to normal IC neurons. The latter two findings may be related to the deficit of hearing which is reported in the GEP rat. The increased incidence of onset-offset responses may be due to a decreased efficacy of inhibition in the GEP rat neurons as compared to normal rat neurons.

Acoustic Stimulation↗
PubMed1986

Abnormality of alpha 1-adrenergic receptors in the frontal cortex of epileptic rats.

We found that the binding of [3H]prazosin, a selective ligand for alpha 1-adrenergic recognition sites, is significantly lower in the frontal cortex of the genetically epilepsy-prone rats (GEPRs), as compared with normal Sprague-Dawley rats. Scatchard analysis reveals a decrease in the Bmax of [3H]prazosin binding with no change in the apparent KD, suggesting that there are fewer alpha 1-adrenergic recognition sites in the frontal cortex of the GEPR. This abnormality is associated with a reduced capacity of norepinephrine (NE) to stimulate [3H]inositol monophosphate ([3H]IP1) formation in frontal cortex slices prelabeled with [3H]inositol. No significant differences in [3H]prazosin binding as well as NE-stimulated [3H]IP1 formation have been observed in other brain regions including hippocampus, corpus striatum, and inferior colliculus. These results indicate that a deficit in the alpha 1-adrenergic receptor system in the frontal cortex may play a role in the seizure process in the GEPR.

Animals↗
PubMed1985

Intracerebroventricular administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium ion (MPP+) decrease dopamine and increase acetylcholine in the mouse neostriatum.

We found that both MPTP and its metabolite MPP+ decrease dopamine and increase acetylcholine content of mouse neostriatum when administered intracerebroventricularly (ICV). These observations support the notion that MPP+ may be the active neurotoxin formed in brain after MPTP administration. They also suggest that cholinergic mechanisms may be a target of the neurotoxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine increases acetylcholine and decreases dopamine in mouse striatum: both responses are blocked by anticholinergic drugs.

The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathology and clinical symptoms that resemble Parkinsonism in primates and humans. In mice it induces a long-lasting depletion of neostriatal 3,4-dihydroxyphenylethylamine (dopamine) content. Using the mouse, we found that MPTP induces a fall of dopamine and a rise of acetylcholine in the neostriatum. Both responses to MPTP can be blocked by prior treatment with atropine or trihexyphenidyl.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Neurotransmitter abnormalities in genetically epileptic rodents.

A growing body of evidence supports a pathophysiological role for norepinephrine (NE) and serotonin in the regulation of seizures in the genetically epilepsy-prone rat (GEPR). Other evidence indicates that gamma-aminobutyric acid (GABA) and taurine may also participate in the seizure regulation process. Innate deficits in NE and serotonin appear to be causes of the genetically determined seizure-prone states of the GEPR, whereas abnormalities in GABAergic systems and taurine metabolism may represent inadequate attempts of the central nervous system to compensate for the seizure-prone state in these rats. In audiogenic seizure-susceptible (AGS) mice, evidence suggests a role for dopamine as well as GABA and possibly serotonin. NE may contribute to the regulation of seizures in AGS mice, but consistent evidence for a primary role for this monoamine is lacking. It is suggested that there is no single common neurotransmitter abnormality underlying genetic seizure disorders in humans or other animals and that the GEPR and the AGS mouse may both serve as good models for study of the neurochemical abnormalities that underlie the different human epilepsies.

Acoustic Stimulation↗
PubMed1982

Abnormalities in monoamine levels in the central nervous system of the genetically epilepsy-prone rat.

Norepinephrine, dopamine, and 5-hydroxytryptamine concentrations were determined in the central nervous systems of genetically epilepsy-prone rats (GEPR) and in control rats. Norepinephrine concentrations were abnormal in all major areas of the central nervous system of the GEPR, with decrements existing in the telencephalon, hypothalamus-thalamus, midbrain, pons-medulla and spinal cord. An increment in the concentration of this neurotransmitter existed in the cerebellum. Dopamine concentrations were normal in all areas of the GEPR brain. Abnormalities in 5-hydroxytryptamine concentrations were also present in the GEPR. They were exclusively decrements and occurred in the telencephalon, hypothalamus-thalamus, midbrain, and pons medulla. Concentrations of this neurotransmitter were normal in the cerebellum and spinal cord. Coupled with our earlier pharmacologic data, these observations support our concept that noradrenergic and/or 5-hydroxytryptaminergic decrements are etiologically important in seizure susceptibility in the GEPR. The lack of abnormalities in brain dopamine concentrations strengthens our hypothesis that dopaminergic transmission does not regulate seizure susceptibility in this model.

Animals↗
PubMed1976

The interaction of delta9-tetrahydrocannabinol with cholinomimetic drugs in an agonist-antagonist paradigm.

In rabbits, i.v. delta9-tetrahydrocannabinol (delta9-THC) at 0.5 mg/kg was challenged with i.v. arecoline (0.025 mg/kg), nicotine (0.02 mg/kg) or physostigmine (PHYSO, 0.05 mg/kg), and observations were made on quantified EEG and behavior. The cholinomimetics effectively reversed the cortical and hippocampal EEG alterations induced by delta9-THC. Arecoline and PHYSO temporarily reversed the behavioral-sedative effects of delta9-THC whereas the combination of delta9-THC with nicotine produced behavioral collapse preceded by behavioral disturbance.

Animals↗
PubMedDate not supplied

Effect of midbrain and pontine tegmental lesions on audiogenic seizures in genetically epilepsy-prone rats.

A bilateral mechanical lesion of the midbrain and pontine tegmentum was found to abolish completely the tonic components of sound-induced seizures in genetically epilepsy-prone rats (GEPR) that display tonic-clonic seizures. Correlations between varied lesions placements and effects on maximal audiogenic seizures provided evidence that damage to the nucleus reticularis pontis oralis (RPO) of the midbrain and pontine reticular formation (RF) was responsible for the seizure-attenuating effects. Moreover, electrolytic lesions of the pontine RF involving the RPO nucleus were found to abolish the tonic components of the maximal audiogenic seizure. Additionally, bilateral mechanical lesions involving the RPO nucleus were found to attenuate the clonic components of sound-induced seizures in GEPR that display only running seizures and clonus. These findings are consistent with previous studies showing that pontine tegmental lesions attenuate the tonic components of maximal electroshock- and pentylenetetrazol-induced seizures, and lend further support to the hypothesis that all generalized tonic seizures share a common neural substrate. The role of the brainstem RF in tonic versus clonic convulsions is discussed in light of the present findings.

Acoustic Stimulation↗
PubMedDate not supplied

The status of vitamin B6 metabolism in brains of genetically epilepsy-prone rats.

The status of vitamin B6 in brains of genetically epilepsy-prone and epilepsy-resistant rats was ascertained by measuring the concentrations of pyridoxal phosphate and the activities of pyridoxal kinase in the hippocampus, basal ganglia, cerebellum, and cerebral cortex, as well as in the entire brain. The concentrations of pyridoxal phosphate in whole brain of control rats and seizure-prone rats did not vary significantly from each other and were 1.2 +/- 0.02 and 1.2 +/- 0.03 microgram/g, respectively. Similarly, the activities of pyridoxal kinase in brains of the two groups were uniform and had values of 3.6 +/- 0.1 and 3.5 +/- 0.06 microgram pyridoxal phosphate formed/mg protein/15 min, respectively. Unlike in the whole brain, the concentration of pyridoxal phosphate in the cerebral cortex of seizure-prone rats was lower (1.24 +/- 0.026 microgram/g) than that of seizure-resistant rats (1.47 +/- 0.23 microgram/g). The opposite was noted in the cerebellum. The concentrations of pyridoxal phosphate in the hippocampus and in the basal ganglion of seizure-prone and seizure-resistant rats were identical. The activities of pyridoxal kinase in the basal ganglion (3.84 +/- 0.23 vs. 4.99 +/- 0.11 microgram pyridoxal phosphate/mg protein/15 min) and in the cerebral cortex (3.40 +/- 0.06 vs. 3.70 +/- 0.04 microgram pyridoxal phosphate/mg protein/15 min) were lower in seizure-prone rats than in seizure-resistant rats. The reverse took place in the hippocampus and in the cerebellum. No uniform associations among the concentration of pyridoxal phosphate, the activity of pyridoxal kinase, and the susceptibility or lack of susceptibility to seizure could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗