Biomedical subjects

J S Fink

Publications and source records attributed to J S Fink.

60 records · Page 4Linked to original sources

PubMed1979

Abnormal pattern of amphetamine locomotion after 6-OHDA lesion of anteromedial caudate.

6-Hydroxydopamine (6-OHDA) injections into the anteromedial caudate nucleus (AMCN) produced severe loss of dopamine (DA) fibers in this region of the caudate. After a low dose of d'amphetamine (1.5 mg/kg), AMCN 6-OHDA rats made fewer traverses of the length of the activity cage than control rats. In contrast, AMCN 6-OHDA rats interrupted a photocell bema that passed across the middle of the long axis of the activity cage as often as control rats. 6-OHDA injections into the nucleus accumbens (NAc) produced severe loss of DA fibers in NAc without significantly damaging the adjacent anteromedial caudate or olfactory tubercle. After d-amphetamine (1.5 mg/kg), NAc 6-OHDA rats interrupted the photocell beam and traversed the length of the activity cage as frequently as control rats. We conclude that the DA innervation to the anteromedial caudate, but not to the nucleus accumbens, is necessary for that part of the normal locomotor response to a low dose of d'amphetamine that is required for the performance of long traverses of an activity cage.

Animals↗

PubMed1979

L-Dopa repairs deficits in locomotor and investigatory exploration produced by denervation of catecholamine terminal fields in the forebrain of rats.

In a previous study rats were shown to have decreased locomotor and investigatory exploration after bilateral microinjections of 6-hydroxydopamine into the anterolateral hypothalamus. These deficits correlate with the loss of catecholamine terminals in neocortical, limbic, and anteromedioventral striatal brain sites. To test whether this correlation was causal, central catecholamines were increased by the intraperitoneal administration of L-3,4-dihydroxyphenylalanine (L-dopa), 10--40 mg/kg) after inhibition of extracerebral L-amino acid decarboxylase. Such treatment repaired the deficits in locomotor exploration and investigation in 6-hydroxydopamine rats. Pretreatment with the catecholamine antagonist chlorpromazine (1--2 mg/kg) blocked the increase in locomotor exploration and investigation produced by L-dopa in 6-hydroxydopamine rats. The results suggest, but do not prove, that L-dopa produced these behavioral effects by increasing central catecholamines at the denervated catecholamine receptor sites in the forebrain. These data and the data from the previous study are complementary evidence for the hypothesis that forebrain catecholamine synaptic action is necessary for normal exploratory behavior.

Animals↗

PubMed1979

Decreased locomotor and investigatory exploration after denervation of catecholamine terminal fields in the forebrain of rats.

Exploratory behaviors were examined after bilateral microinjections of 6-hydroxydopamine into two hypothalamic sites that produced different patterns of denervation of forebrain catecholamine terminal fields. After anterolateral injections rats locomoted and reared less in a novel open field, responded abnormally to changes in the degree of novelty of the open field, and investigated a novel object less. These are deficits in exploratory behavior because they were not secondary to the inhibition of open-field behavior by hyperemotionality, by general motor disability, or by the failure to detect novel spaces or objects. Such anterolateral injections produced loss of catecholamine fibers, determined histochemically, in neocortical, hippocampal, anterolateral hypothalamic, mesolimbic, mesocortical, and anteromedioventral striatal terminal fields and loss of dopaminergic perikarya in the A10 and anteromedial A9 cell groups. No deficits in exploratory behaviors occurred, however, after bilateral anteromedial 6-hydroxydopamine injections that denervated neocortical, hippocampal, and anteromedial hypothalamic catecholamine terminal fields. A critical forebrain catecholaminergic innervation for exploratory responses to novel stimuli may be within areas that were denervated by anterolateral but not by anteromedial hypothalamic 6-nydroxydopamine injections. These areas are mesolimbic, mesocortical, anteromedioventral, and anterolateral hypothalamic terminal fields.

Animals↗

PubMed1977

Different behavioral responses to L-DOPA after anterolateral or posterolateral hypothalamic injections of 6-hydroxydopamine.

After bilateral microinjections of 6-hydroxydopamine (6-OHDA) into the anterolateral (AL) or posterolateral (PL) hypothalamus L-DOPA (1,3,4-dihydroxy-phenylalanine) produced running and rearing in AL6-OHDA rats and oral stereotypies in PL 6-OHDA rats. Since the same dose of L-DOPA had no behavioral effect in vehicle injected rats, the responses to L-DOPA of both AL and PL 6-OHDA rats are examples of behavioral supersensitivity. The different forms of behavioral supersensitivity correlated with different patterns of catecholamine (CA) denervation determined by fluorescent microscopy. The major regions of CA denervation in AL 6-OHDA rats were neocortex, hippocampus, limbic forebrain, anteromedial striatum and anterolateral hypothalamus. PL 6-OHDA had these same areas denervated and, in addition, had severe denervation of the entire striatum, parts of the amygdala and thalamus, and of the posterolateral hypothalamus. We conclude that the supersensitive behavioral response to a fixed dose of L-DOPA is determined by the pattern and/or extent of CA denervation.

Afferent Pathways↗

PubMedDate not supplied

Biosynthesis of pancreatic islet hormones.

We have outlined the various strategies used to characterize the precursors of three pancreatic islet hormones--somatostatin, pancreatic polypeptide and VIP. In each case, isolation of the cDNA clones was facilitated by the use of gastrointestinal tissues that were extremely rich in specific mRNA. Characterization of the structures of the precursors is clearly only the first step in understanding the regulation of pancreatic hormone biosynthesis. It is likely that the availability of the cDNA clones will allow us to define the actual mechanisms underlying hormone production within the pancreas.

Animals↗

PubMedDate not supplied

Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results.

The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.

Adult↗