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Biomedical subjects

A Jayaraman

Publications and source records attributed to A Jayaraman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation.

The powerful psychostimulant and positive reinforcing effects of nicotine have been speculated to be mediated by the dopaminergic neurons of the ventral tegemental area (VTA) and their terminals in the nucleus accumbens. To extend our understanding of nicotine and dopamine interactions, we mapped the pattern of c-fos expression in the striatum as an important marker of some of the earliest changes that occur at gene transcription level. Acute nicotine injections in rats led to Fos expression more prominently in the caudatoputamen than in the nucleus accumbens in a dose-dependent fashion. Fos-reactive cells were more prominent in the central and dorsomedial limbic caudatoputamen than in the dorsolateral sensory-motor striatum. Injections of mecamylamine completely blocked nicotine-induced Fos expression. Injections of the selective dopamine D1 antagonist SCH 23390, but not D2 antagonist YM 09151-2 or Clozapine, a drug with high affinity to D4 receptors, before nicotine injections, completely blocked Fos expression in the striatum. Nicotine induced Fos expression was also blocked completely by the NMDA receptor antagonists MK-801 and CPP. These results suggest that nicotine-induced Fos expression in the striatum is mediated mostly by dopamine D1 receptors and that the Fos expression is also dependent on N-methyl-D-aspartate (NMDA) stimulation.

Animals↗
PubMed1993

Acute nicotine injections induce c-fos mostly in non-dopaminergic neurons of the midbrain of the rat.

Induction of c-fos gene is an immediate and early response in the cascade of molecular events that ultimately lead to long-term alterations in gene expression in neurons. The psychomotor stimulant and positive reinforcing effects of nicotine have been speculated to be mediated by the dopaminergic neurons of the ventral tegmental area (VTA). To identify the precise subsets of VTA neurons of the rat that mediate the acute nicotinergic effects, the pattern of expression of c-fos gene was mapped using immunocytochemical methods. Acute nicotine injections resulted in prominent Fos-like immunoreactivity (-LI) in the medial terminal nucleus of the accessory optic system, the interpeduncular nucleus, and in the caudal linear subnucleus of VTA. The neurons of other VTA subnuclei, viz., the rostral linear, paranigralis, nucleus parabrachialis pigmentosus, and nucleus interfascicularis or the substantia nigra pars compacta did not contain any cells with Fos-LI. Mecamylamine abolished Fos-LI in most of the VTA neurons. These results suggest that acute nicotine injections induce c-fos expression mostly in non-dopaminergic neurons of the ventral tegmental area of the rat and that nicotine induces c-fos most intensely in the interpeduncular nucleus, the superior colliculus, and several other subnuclei of the accessory optic system.

Animals↗
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↗