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Biomedical subjects

A Jayaraman

Publications and source records attributed to A Jayaraman.

At least 19 recordsLinked to original sources
PubMed1990

Cholecystokinin and neurotensin mRNAs are differentially expressed in subnuclei of the ventral tegmental area.

Immunohistochemical studies of ventral tegmental area (VTA) neurons indicate that individual cells can contain dopamine as well as the neuropeptide neurotransmitters cholecystokinin (CCK) and neurotensin (NT). We have defined the distribution of the cells expressing the mRNAs encoding these two dopamine cotransmitter peptides in each of the subnuclei of the ventral tegmental area, and quantitated the extent of expression of each gene by using in situ hybridization methods. These studies reveal significant differences in the patterns of expression of each of these two genes within various subdivisions of the VTA. The rostral linear nucleus contained numerous CCK positive cells, some of which appeared to express preproCCK-mRNA at a very high level, but this nucleus contained relatively few NT-expressing cells. The parabrachialis pigmentosus contained numerous NT and CCK positive cells. The paranigralis and interfascicularis nuclei displayed positive CCK cells but with expression at only modest levels. NT cells were very few in these nuclei. The caudal linear nuclei contained the highest number of NT-expressing neurons and these cells expressed very high levels of NT mRNA. The selective distribution of these peptide genes within the VTA subnuclei may have specific consequences. Studies of the connectivity of neurons in the VTA show that the different subnuclei of this region project to several functionally and architectonically different regions of the cerebral cortex and subcortically to nuclei related to the limbic system. Results from our study show very prominent expression of CCK mRNAs in those subnuclei that project heavily to the prefrontal, other cortical areas, and the amygdaloid complex. The NT gene is expressed prominently in those subnuclei of VTA that project heavily to the entorhinal cortex and amygdaloid complex. These results provide support for a differential role for the NT-expressing neurons than that of CCK-expressing neurons of VTA in "reward" mechanisms and in drug-seeking and motivational behavior. These observations could be applied to create working hypotheses and experimental paradigms to test the differential functional activity of the subdivisions of VTA and their potential roles in the pathogenesis and treatment of drug-seeking behavior and other neuropsychiatric disorders.

Animals↗
PubMed1990

Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.

Retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was studied in 7 squirrel monkeys with discrete injections of the subthalamic nucleus (STN). Injections labeled: (1) the lateral two-thirds of the nucleus (63% and 47%), (2) ventrolateral parts caudally (20%), (3) dorsomedial parts caudally (18%), (4) rostromedial parts (21%), (5) the medial third (38%) and (6) the lateral pole of the nucleus (9%). Afferents to the lateral two-thirds of the STN originated from two parallel cellular arrays in dorsal parts of the middle third of the lateral pallidal segment (LPS) and a single array in the rostral third of the LPS. Medial regions of the STN received input from cells in the rostral LPS. Small numbers of cells were retrogradely labeled in the centromedian-parafascicular (CM-PF) and the pedunculopontine (PPN) nuclei. No cells were labeled in the frontal cortex, the striatum, the substantia innominata (SI), the substantia nigra (SN) or the dorsal nucleus of the raphe. Virtually all pallidal neurons, including identified pallidosubthalamic neurons, were immunoreactive (IR) for gamma-aminobutyric acid (GABA). Pallidosubthalamic neurons were most numerous in regions of the LPS with the lowest density of leucine enkephalin-IR fibers. Substance P-IR fibers, found mainly in the medial pallidal segment, bore no relationship to pallidal afferents to the STN. Choline acetyltransferase-IR cells in the SI and the PPN were not retrogradely labeled with WGA-HRP granules. Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS, suggesting a reciprocal relationship. The caudal third of the LPS and ventral region of the middle third of this nucleus, appeared to project few fibers to, or to receive few fibers from, the STN. A small number of STN efferents entered the medial border of the putamen, but no terminal fields were identified. STN projections to the pars reticulata of the SN appeared to represent about 10% of the projection to the LPS. No STN efferents were identified in the frontal cortex, the SI or the PPN. The hypothesis that STN afferents from the frontal cortex and CM-PF may represent collaterals of projections to other loci is discussed.

Animals↗
PubMed1988

Distribution pattern of cell bodies and fibers with neurotensin-like immunoreactivity in the cat hypothalamus.

Neurotensin is widely distributed in the central and peripheral nervous systems. Extensive radioimmunoassay and immunohistochemical studies in rats show that the neurotensin immunoreactive perikarya and fibers are most prominent in the hypothalamus. Radioimmunoassay studies have suggested that the levels of neurotensin in the hypothalamus of cats may be six times higher than that of rats. We studied the distribution pattern of neurotensin immunoreactivity within the hypothalamus of the cat by avidin-biotin modification immunohistochemical methods: (1) to define its distribution pattern within the hypothalamus, and (2) to compare our findings with the patterns that have been described in rats. Results show that neurotensin immunoreactive cell bodies and fibers are most prominent in the rostral and intermediate regions of the cat hypothalamus. Cell bodies with neurotensin-like immunoreactivity are seen maximally in the medial preoptic region, the infundibular nucleus, and the lateral hypothalamus. The neurotensin positive fibers are dense in the periventricular regions of the entire rostro-caudal extent of the hypothalamus. This pattern of distribution of neurotensin immunoreactivity is similar to that described in rats. The suprachiasmatic nuclei of the cat hypothalamus, however, contained a significant number of neurotensin immunoreactive cell bodies, an observation not noted in the rat hypothalamus. The neurotensin immunoreactive neurons were more numerous in the lateral hypothalamus than has been reported in rats, but the paraventricular nucleus of the hypothalamus in cats contained fewer neurotensin immunoreactive perikarya. The presence of neurotensin immunoreactive perikarya in the suprachiasmatic nucleus and the apparent increase in the number of neurotensin immunoreactive neurons in the lateral hypothalamus may account for the increased levels of neurotensin reported in cats. Neurotensin has been speculated to play a role in nociception, thermoregulation, and control of arterial pressure by acting as a hormone or a neurotransmitter. Details of the pattern of colocalization of neurotensin with that of other neuropeptides and neurotransmitters will aid in our understanding of its role in these functions.

Animals↗
PubMed1987

Thyrotropin-releasing hormone and cyclo (His-Pro)-like immunoreactivities in the cerebrospinal fluids of 'normal' infants and adults, and patients with various neuropsychiatric and neurologic disorders.

Levels of thyrotropin-releasing hormone (TRH) - and cyclo(His-Pro) (CHP)-like immunoreactivities and the activity of enzyme Pyroglutamate aminopeptidase (PAPase) were measured in cerebrospinal fluid (CSF) of over 100 normal adults (NA) and infants, and adult patients with various neurologic and neuropsychiatric disorders (NNDA). Levels of TRH and CHP in CSF of over 70% of the NA group were below 50 and 500 pg/ml respectively. The TRH- and CHP-like immunoreactivities in the remainder of the 30% of NA specimens exhibiting higher peptide concentrations were enzymatically and chromatographically characterized and were found to behave like authentic peptides. The levels of both of these peptides were significantly elevated in the CSF of most of the NNDA patients. An elevation in the CSF level of CHP was significantly correlated with the level of TRH, but not PAPase. Results from this study suggest that CSF elevation of TRH level may be due to a nonspecific response to stress that may be associated with hospitalization, myelogram procedure, and/or the neurologic and neuropsychiatric diseases for which the patients were admitted.

Adult↗
PubMed1987

Is all cyclo(His-Pro) derived from thyrotropin-releasing hormone?

Cyclo(His-Pro), or histidyl-proline diketopiperazine, is an endogenous cyclic dipeptide that is ubiquitously distributed in tissues and body fluids of both man and animals. This cyclic dipeptide is not only structurally related to thyrotropin-releasing hormone (TRH, pGlu-His-ProNH2), but it can also arise from TRH by the action of the enzyme pyroglutamate amino-peptidase (pGlu-peptidase). The data on the distribution of TRH, cyclo(His-Pro), and pGlu-peptidase under normal and abnormal conditions are summarized and potential relationships analyzed. We conclude that all of the cyclo(His-Pro) cannot be derived from TRH. Two additional sources of cyclo(His-Pro) are suggested. It is proposed that 29,247 molecular weight TRH prohormone, prepro TRH, which contains 5 copies of TRH sequence, can be processed to yield cyclo(His-Pro). Thus, both TRH and cyclo(His-Pro) share a common precursor, prepro[TRH/Cyclo(His-Pro)].

Animals↗
PubMed1987

Pyroglutamate aminopeptidase activity in human cerebrospinal fluid decreases with age.

The activity of pyroglutamate aminopeptidase, the major enzyme catalyzing thyrotropin-releasing hormone (TRH) metabolism in human CSF, decreased with age. This decrement is not due to age-dependent appearance of any enzyme inhibitor in CSF. The results of these studies underline the importance of using age-matched controls in assessing abnormalities of TRH metabolism in CSF during disease states.

Adult↗
PubMed1986

The distribution pattern of adrenocorticotropin-like immunoreactivity in the cat central nervous system.

The distribution pattern of adrenocorticotropin-like immunoreactivity (ACTH-LI) in cats using the avidin-biotin modification of an immunocytochemical method shows cell bodies containing ACTH-LI in the medial basal hypothalamus, especially in the infundibular nucleus. The fibers from these neurons extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus coeruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. The distribution pattern of the cell bodies and fibers containing ACTH-LI bears several similarities to that seen in rats. The pattern differs from that of rats in the fact that the termination in the amygdala is more extensive and that ACTH-LI was not observed in cell bodies in any location other than the medial basal hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1986

Distribution and characterization of cyclo(His-Pro)-like immunoreactivity in human cerebrospinal fluid.

The distribution of cyclo(His-Pro), thyrotropin-releasing hormone and pyroglutamate aminopeptidase activity was examined in the CSF of human and a number of other mammalian species. Cyclo(His-Pro)-like immunoreactivity was present in the CSF of all species examined, and was immunologically and chromatographically identical with the authentic cyclo(His-Pro). Cyclo(His-Pro) concentration in CSF had no significant correlation with CSF TRH or pyroglutamate aminopeptidase.

Adult↗
PubMed1986

Metabolism of thyrotropin-releasing hormone in human cerebrospinal fluid. Isolation and characterization of pyroglutamate aminopeptidase activity.

Pyroglutamate aminopeptidase, which catalyzes metabolism of thyrotropin-releasing hormone (TRH) to cyclo(His-Pro), is the major enzyme of TRH metabolism in human CSF. The partially purified CSF pyroglutamate aminopeptidase has a pH optimum between 6.0 and 7.4, and a Km of 15.9 +/- 3.1 microM. A number of potential competitive inhibitors of the enzymatic activity were examined, of which luteinizing hormone-releasing hormone and bombesin were the most effective. An examination of the structure of various peptides that inhibit pyroglutamate aminopeptidase activity indicated that the enzyme generally prefers a substrate having amino-terminal pyroglutamic acid (pGlu) and a COOH-terminal that is either blocked or distant from amino-terminal pGlu. Heavy metals, EDTA and reducing agents inactivated the enyzme, whereas benzamidine, phenylmethylsulfonylfluoride, trypsin inhibitor and alkylating agents had little or no effect on the enzymatic activity. Thiol-oxidizing agent 5,5'-dithiobis(2-nitrobenzoic acid), however, considerally inhibited the enzymatic activity. We hypothesize that CSF pyroglutamate aminopeptidase may play a role in the biologic actions of TRH.

Aminopeptidases↗
PubMed1985

Organization of thalamic projections in the nucleus accumbens and the caudate nucleus in cats and its relation with hippocampal and other subcortical afferents.

The organization of thalamic projections in the nucleus accumbens (NA) and the caudate nucleus of cats and its relation to other subcortical striatal afferents were studied with a retrograde tracing technique by use of lectin-conjugated horseradish peroxidase. The study showed that the paraventricular and medial parafascicular nuclei (PF) of the thalamus project to the medial NA and the parataenial and medial PF project to the lateral NA. The ventral tegmental area and substantia nigra pars dorsalis (SNpd) project to medial and lateral NA. The midline thalamic nuclei, rostral intralaminar nuclei, ventroanterior nucleus, medial and lateral PF, lateral posterior complex, and nucleus limitans project to medial caudate nucleus. The most medial substantia nigra pars compacta (SNpc) and rostral SNpd project to medial caudate nucleus. The center median, ventrolateral, and the central lateral nuclei of thalamus, SNpc, and SNpd project to lateral caudate nucleus. These results suggest that the thalamic and subcortical nuclei known to connect with the limbic and frontal cortices project to NA and medial caudate nucleus. Those thalamic nuclei connected with the motor system project to lateral caudate nucleus. The hippocampus projects selectively to medial NA. The amygdala, raphe, and other mesencephalic nuclei project only to NA and medial caudate nucleus. The organization of hippocampal, amygdala, and other subcortical afferents suggests that NA and caudate nucleus can be separated into medial "limbic" and lateral nonlimbic "sensory-motor" compartments. A brief review of the distribution pattern of some neurotransmitters, neuropeptides, and their receptors and behavior studies provides additional support to the concept that the striatum can be divided into several subcompartments.

Amygdala↗
PubMed1984

Spatio-temporal processing in multiple sclerosis.

The processing of spatial and temporal detail was investigated in patients with multiple sclerosis. Normal observers and 13 patients with optic neuritis secondary to multiple sclerosis performed a battery of visual tests that included contrast sensitivity, temporal integration, evoked potentials, and visual masking. The multiple sclerosis patients exhibited losses of pattern processing, and these deficits became more noticeable when the patterns were presented briefly. Moreover, these patients exhibited diverse response patterns for the different visual tests. For some, temporal integration functions appeared severely attenuated, while evoked potential latency was within normal limits. Others displayed poor performance in the visual masking test, yet contrast sensitivity functions were comparable to those of the control group. We suggest that a battery of tests that incorporates spatial as well as temporal stimuli is necessary for the detection of visual dysfunction in multiple sclerosis.

Adult↗
PubMed1983

Topographic organization and morphology of peripallidal and pallidal cells projecting to the striatum in cats.

Injections of small amounts of horseradish peroxidase (HRP) or HRP coupled with wheat germ agglutinin within the caudate nucleus in adult cats resulted in retrograde labeling of neurons within the globus pallidus and within the fibers of internal capsule near the globus pallidus. These triangular and fusiform neurons, measuring 27-30 micron, project topographically to the striatum. The morphology and the location of some of the labeled neurons in these cases resemble the acetylcholinesterase-positive neurons of the nucleus basalis magnocellularis described by other authors. The findings from this study support the existence of a projection from the globus pallidus and peripallidal region to the striatum in cats.

Afferent Pathways↗
PubMed1979

Organization of visual cortical projections to the claustrum in the cat.

The projection patterns from different visual areas of the parieto-occipital cortex to the claustrum were studied autoradiographically in cats. When [3H]proline was injected into 17, 18, 19 or Clare-Bishop areas, the label was transported to an area restricted to the dorsal and caudal parts of the claustrum without any suggestion of retinotopic organization. Injection in each of these visual areas resulted in individual patterns of projection but with overlapping fields of termination, a pattern similar to corticocaudate projection. When injected into area 7, a region shown to have neurons involved in visuomotor mechanisms, the label was transported to the same area as that of the visual projection. These and other findings suggest that claustrum may be reciprocally and topographically connected with the cerebral cortex.

Animals↗