Biomedical subjects

W R Lin

Publications and source records attributed to W R Lin.

23 records · Page 2Linked to original sources

PubMed1992

Fluoxetine and 8-OH-DPAT in the lateral septum enhances and impairs retention of an inhibitory avoidance response in rats.

The present study investigated the role of lateral septal serotonin (5HT) in memory consolidation and the subtype of 5HT receptors involved in this process. Rats with cannulae implanted bilaterally into the lateral septum were trained in an inhibitory avoidance task. Immediately after training, the septal serotonergic function was manipulated by pharmacological agents selectively blocking 5HT reuptake (fluoxetine and zimelidine), antagonizing 5HT2 receptors (ketanserin and ritanserin), or activating 5HT1A receptors, respectively. Results indicated that direct fluoxetine infusions into the lateral septum at a dose of 6 micrograms/0.5 microliter and zimelidine at a dose of 5 micrograms/0.5 microliter both markedly enhanced memory. Intralateral septal injections of ketanserin (0.3 microgram/0.5 microliter and 0.5 microgram/0.5 microliter) and ritanserin (0.3 microgram/0.5 microliter and 0.6 microgram/0.5 microliter) did not have a significant effect by themselves on memory, and neither did they attenuate the memory-facilitating effect of fluoxetine in the same area. Intralateral septal infusions of 8-hydroxy-2-(di-n-propylamino)tetralin at 5 micrograms/0.5 microliter significantly impaired memory retention. These findings altogether support the notion that the lateral septal nuclei of rats are involved in the memory processes of inhibitory avoidance learning. Furthermore, postsynaptic 5HT receptor activation (not the 5HT2 receptor subtype) probably exerts a facilitatory effect while presynaptic 5HT1A receptor activation exerts an impairing effect on the memory consolidation process, probably due to autoreceptor inhibition of 5HT release.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Comparative studies of the neurotoxicity of MPTP in rats of different ages.

The present study investigated the neurotoxic effects of repeated MPTP injections on monoamine neurotransmitters and locomotor activity in rats of different ages. We also examined the mortality of MPTP-treated rats at different ages. Male Sprague-Dawley rats were used in all experiments. In the first experiment, we examined the mortality of rats (11-12 month old) subject to different doses of MPTP. In the second experiment, rats of 2-3 months old were randomly divided into five groups. Group 1 served as the control; Groups 2,3,4 and 5 received daily MPTP injections (30 mg/kg, ip) for a continuation of 7 days. Biochemical and behavioral assays were conducted at 1,7,14 and 28 days after withdrawal of MPTP, respectively. In the third and fourth experiments, the same experimental design was adopted except that rats of 5-6 months old and rats of 11-12 months old were used, respectively. Besides, the doses of MPTP used were 22.5 mg/kg and 12.5 mg/kg, respectively. Immunohistochemical experiments were always conducted 7 days after withdrawal of MPTP. Results indicated that, in young rats, repeated MPTP injections did not significantly decrease DA, and 5HT levels as well as TH and DBH immunoreactivities although it impaired locomotor activity. The same treatment significantly depleted DA, NE and 5HT levels in the middle-aged rats. It also decreased the density of TH and DBH immunoreactivities and altered the morphology of DA and NE neurons. Meanwhile, it impaired locomotor activity. In old rats, MPTP injections produced effects similar to those observed in the middle-age rats except that the hippocampal serotonergic system was also affected. However, all these effects recovered 28 days after withdrawal of MPTP injection. Finally, the dose of MPTP required to exert similar extent of neurotoxicity decreased as the age of rats increased, and the dose required to result in mortality markedly decreased in old rats. These results together suggest that MPTP does exert a toxicity on DA, NE and 5HT neurons and impair motor activity in rats. These effects are age-dependent while the irreversibility of MPTP's toxicity in rats requires further investigation.

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

PubMed1991

Nifedipine and verapamil block the memory-facilitating effect of corticotropin-releasing factor in rats.

The effects of two calcium channel blockers, nifedipine and verapamil, and the peptide corticotropin releasing factor (CRF) as well as their interactive effects on memory retention were examined in rats. Male Sprague-Dawley rats were chronically cannulated bilaterally and drugs were directly injected into the dentate gyrus of the hippocampus. Animals were trained in a one-way inhibitory avoidance task and memory was measured 24 h later. Results indicate that there was a U-shaped dose-response curve for the effects of nifedipine and verapamil with nifedipine at 8 micrograms and verapamil at 1 microgram both impaired memory formation, while CRF at 0.1 microgram enhanced this process. Nifedipine at 2 micrograms and verapamil at 0.5 microgram, which did not have significant effects on memory by themselves, antagonized the memory-enhancing effect of CRF in the hippocampus. These results suggest that under normal physiological conditions, calcium influx may play an important role in memory consolidation process in the vertebrate.

Animals↗

PubMedDate not supplied

Neurotropic viruses and Alzheimer disease. Interaction of herpes simplex type 1 virus and apolipoprotein E in the etiology of the disease.

Infectious agents have been proposed as possible etiological factors in sporadic cases of Alzheimer disease (AD), herpes simplex type 1 virus (HSV1) being a likely candidate. We have detected laten HSV1 in brain from AD patients and from aged normal individuals, using polymerase chain reaction (PCR), in the regions most affected in the disease. In contrast, we have not detected another neurotropic herpes virus, varicella zoster (VZV), in any brains. We have postulated that HSV1 reactivates periodically, and that a host or viral characteristic determines the degree of damage caused by the resulting acute infection-with much greater damage in the case of AD patients. We have therefore examined a host factor-the apolipoprotein E (apoE) genotype, since the E4 allele is a known risk factor in the disease. We have found that the risk of developing AD is much greater in those who are HSV1-positive in brain and who possess an apoE4 allele than for those with only one of these factors.

Aged↗

PubMedDate not supplied

Vaccination prevents latent HSV1 infection of mouse brain.

Herpes simplex encephalitis (HSE) is a rare but very serious disorder caused by herpes simplex type 1 virus (HSV-1). Treatment with acyclovir decreases mortality but many patients still suffer cognitive impairment subsequently. A vaccine against HSV1 would therefore be of great value. HSV-1 has been implicated also in Alzheimer's disease (AD): we established that HSV1 resides in the brain of about two thirds of AD patients and aged normal people, and that in carriers of the type 4 allele of the apolipoprotein E gene, it is a strong risk factor for AD. Thus a vaccine against HSV-1 might prevent development of AD in some cases. To find whether a vaccine of mixed HSV-1 glycoproteins (ISCOMs), which protects mice from latent HSV-1 infection of sensory ganglia, prevents HSV1 latency in the CNS, ISCOM-vaccinated or unvaccinated animals were infected with HSV-1. Using polymerase chain reaction (PCR) we detected HSV-1 in brain from 16 of 39 unvaccinated mice (41%), but only 3 of 41 vaccinated mice (7%) (P < 0.001). Thus, ISCOMs protect the CNS also, suggesting their possible future usage in humans.

Alzheimer Disease↗