Nitric oxide-containing neurons in long-term grafts in a rat model of Parkinson's disease.

The role that nitric oxide may play in modulating graft function in long-term fetal ventral mesencephalic grafts in an animal model of Parkinson's disease was investigated. Mature grafts harvested from the entire fetal ventral mesencephalon possessed a large number of neuronal nitric oxide synthase (nNOS)/NADPH-diaphorase-containing neurons throughout the graft intermingled with dopaminergic neurons. The morphological and neurochemical characteristics of these NADPH-diaphorase neurons resembled those in centers adjacent to the substantia nigra of adult brain but not that of the striatum.

Glutamatergic regulation of long-term grafts of fetal lateral ganglionic eminence in a rat model of Huntington's disease.

Transplanting fetal striatal tissue is currently considered to be an important alternative strategy in the treatment of Huntington's disease. Although grafted striatal tissue differentiates and shows certain structural and neurochemical features of the normal striatum and receives host afferents, it is not clear whether host-derived afferent inputs can modulate the activity of neurotransmitter receptors and their signaling in the graft. An intricate interaction between dopaminergic and glutamatergic systems is pivotal for striatal function.

Muscarinic, adenosine A(2) and histamine H(3) receptor modulation of haloperidol-induced c-fos expression in the striatum and nucleus accumbens.

It is generally believed that haloperidol exerts its motor side effects and therapeutic effects mainly by antagonizing dopamine D(2) receptors in the striatum and the nucleus accumbens, respectively. Several neurotransmitters/modulators, including glutamate, acetylcholine, adenosine and histamine, affect dopaminergic activity in these centers. We have recently shown that N-methyl-D-aspartate receptor-mediated modulation of haloperidol-induced c-fos expression differs in functionally specific regions of the striatum and the nucleus accumbens.

Glutamatergic regulation of haloperidol-induced c-fos expression in the rat striatum and nucleus accumbens.

Acute administration of haloperidol induces the expression of the immediate-early gene c-fos in the striatum and nucleus accumbens via dopamine D(2) receptor antagonism. Dopaminergic transmission in the striatum and nucleus accumbens is modulated by glutamate via N-methyl-D-aspartate (NMDA) receptors. Indeed, haloperidol-induced c-fos expression is dependent on NMDA receptor activation in the dorsolateral part of the striatum.

Changes in CArG-binding protein A expression levels following injection(s) of the D1-dopamine agonist SKF-82958 in the intact and 6-hydroxydopamine-lesioned rat.

We recently characterized the rat brain homolog of mouse muscle CArG-binding protein A initially identified in C2 myogenic cells and showed an inverse temporal correlation between increased expression levels of this messenger RNA, c-fos and zif268 messenger RNA levels following the addition of nerve growth factor to PC12 cells. In addition, we found an inverse correlation between c-Fos protein and CArG-binding protein A messenger RNA levels in the lateral caudate-putamen of rats treated acutely and chronically with the D2 receptor antagonist fluphenazine (phenothiozine typical psychotic). To determine whether D1 receptor stimulation is also capable of inducing CArG-binding protein A up-regulation, drug naive or dopamine-depleted (i.

Characterization of CArG-binding protein A initially identified by differential display.

While investigating differences in the pattern of gene expression in functionally distinct areas of the rat caudate-putamen employing differential display, we identified a gene that is highly enriched in tissue adjacent to the lateral ventricle. To characterize the gene, a complementary DNA containing the complete coding sequence was obtained and sequenced. In addition, radiolabelled DNA and riboprobes were generated to examine the expression levels and anatomical distribution of the identified gene in the brain.

A kappa opioid antagonist blocks sensitization in a rodent model of Parkinson's disease.

Treatment of Parkinson's disease with levodopa is associated with fluctuations in motor function and dyskinesias, which may in part depend upon the mode of levodopa treatment. In rats with unilateral 6-hydroxydopamine lesions, intermittent levodopa results in sensitization to apomorphine-induced rotation, associated with massive ipsilateral increases in nigral dynorphin. We assessed the effects of nigral infusion of the selective kappa opioid antagonist nor-binaltorphomine (nor-BNI) in this model.

Effects of graft-derived dopaminergic innervation on the target neurons of patch and matrix compartments of the striatum.

Fetal dopaminergic neurons grafted into the dopamine-depleted striatum have previously been shown to normalize neurochemical and behavioural abnormalities. However, the extent of graft-induced recovery of striatal compartments, which differ in their ontogeny, neurochemical properties and function, is still not clear. The striosome and matrix compartments of the striatum provide a segregated projection to somatostatin-containing GABAergic neurons of the rostral part of the entopeduncular nucleus and somatostatin-negative GABAergic neurons of the caudal part of the entopeduncular nucleus, respectively.

Somatostatin and the patch/matrix compartments of the rat caudate-putamen.

In the caudate-putamen of the rat, two subpopulations of medium aspiny neurons exist that contain somatostatin. The first subpopulation contains somatostatin 14, somatostatin 28, and somatostatin 28(1-12). The other subpopulation contains only somatostatin 28.

Colocalization of somatostatin, neuropeptide Y, and NADPH-diaphorase in the caudate-putamen of the rat.

Somatostatin, neuropeptide Y, and nicotinamide adenine dinucleotide phosphate-diaphorase are colocalized within a small population of medium aspiny neurons in the caudate-putamen of the rat. The extent of colocalization, however, appears to be in dispute. In order to examine the question of colocalization between these three neuroactive substances, a series of double-labelling experiments was performed.

Parvalbumin-containing GABAergic neurons in the basal ganglia output system of the rat.

The output of the basal ganglia is directed through the entopeduncular nucleus (EPN) and the substantia nigra pars reticulata (SNR) and pars lateralis (SNL), which provide a gamma-aminobutyric acidergic (GABAergic) projection to various nuclei of the thalamus and brainstem. Although many neurons within the SNR and EPN have been described as modality specific, the morphological and neurochemical similarities preclude their precise identification. In the present study, the immunocytochemical localization of parvalbumin, a calcium-binding protein, is used in combination with axonal tracing to verify neuronal heterogeneity within the SNR, SNL, and EPN.

Colocalization of prosomatostatin-derived peptides in the caudate-putamen of the rat.

In the striatum of rat, somatostatin 14, somatostatin 28, and somatostatin 28(1-12) have previously been localized within a small population of medium aspiny local circuit neurons. Because all three peptide fragments are generated through the cleavage of prosomatostatin by different converting enzymes, the possibility for differential expression of these peptides exists. In order to investigate this possibility, frozen sections were collected from the brains of adult female Wistar rats fixed with 4% paraformaldehyde and double labelled using immunocytochemistry and in situ hybridization.

Neurochemical compartmentalization of the globus pallidus in the rat: an immunocytochemical study of calcium-binding proteins.

The globus pallidus external segment forms a major target center of the mammalian striatum which is characterized by neurochemically distinct compartments. The present study was undertaken to determine if a corresponding compartmentalization exists within the globus pallidus external segment in the rat. Immunocytochemical examination of the calcium-binding proteins parvalbumin and calbindin D28kDa, which are present in neurons of the striatal matrix compartment, was employed.

The pallidostriatal projection in the rat: a recurrent inhibitory loop?

The pallidostriatal projection in the rat was investigated employing the PHA-L tracing technique. Following inotophoretic injections into the lateral aspect of the globus pallidus external segment, the ipsilateral striatum showed patches of dense anterograde labeling separated by areas containing sparse anterograde labeling and isolated retrogradely labeled neurons. The densely labeled patches did not correspond to any known compartments of the striatum.

GABAergic synaptic interactions in the substantia nigra.

The substantia nigra receives a strong GABAergic input from the ipsilateral striatum and globus pallidus. Nigral GABAergic synaptic interactions have been described in the pars compacta (SNC) and pars reticulata (SNR) but not in the pars lateralis (SNL). The SNR and particularly the SNL are the nodal points of the GABAergic nigrotectal pathway.

Compartmental origin of the striato-entopeduncular projection in the rat.

The mammalian neostriatum is divisible into neurochemically and cytoarchitectonically distinct striosome and matrix compartments. This compartmentalization is respected by many afferent and efferent projections of the striatum. The distribution of distinct types of neuroactive substances and receptors and the unique connections of the striosome and matrix suggest a functional segregation between these compartments.

Biotinylated dextran: a versatile anterograde and retrograde neuronal tracer.

A powerful and versatile axonal tracing method using biotinylated dextran, a novel analogue of biotin, is described. Pressure injection of varying volumes of 5% biotinylated dextran into various parts of the brain and spinal cord resulted in Golgi-like retrograde labeling and PHA-L-like anterograde labeling. The tracer filled the finest processes, revealing terminal axonal ramifications, distal dendrites and dendritic spines and excrescences.

Normalization of striatal proenkephalin and preprotachykinin mRNA expression by fetal substantia nigra grafts.

The expression of striatal proenkephalin and preprotachykinin mRNA was studied in Wistar rats following unilateral injections of 6-hydroxydopamine into the nigrostriatal pathway and after grafting dopaminergic fetal cell suspensions into the dopamine-depleted striatum. Striatal dopaminergic deafferentation resulted in an amphetamine-induced rotational asymmetry, an increase in ipsilateral striatal proenkephalin mRNA, and a decrease in preprotachykinin mRNA expression. Twelve months following grafting, proenkephalin and preprotachykinin mRNA returned to near-normal levels in contrast to control nongrafted lesioned animals.

Substance P synaptic interactions with GABAergic and dopaminergic neurons in rat substantia nigra: an ultrastructural double-labeling immunocytochemical study.

The distribution of substance P (SP), tyrosine hydroxylase (TH), and glutamic acid decarboxylase (GAD) immunoreactivity in the substantia nigra of the rat was studied by means of an ultrastructural double-labeling immunocytochemical method. Direct synaptic contact between SP-immunoreactive terminals and GAD-positive nigral neurons was more often observed in the pars lateralis than the pars reticularis and was rarely observed in the pars compacta. Substance P-positive terminals also formed synapses with cell bodies and dendrites of TH-positive, dopaminergic neurons in the pars compacta and pars reticulata.

Afferent organization of the lateral reticular nucleus in the rat: an anterograde tracing study.

The organization of the afferent projections to the lateral reticular nucleus of the rat was investigated following placement of horseradish peroxidase-conjugated wheatgerm agglutinin into the red nucleus, fastigial nucleus, various levels of the spinal cord or the sensorimotor area of the cerebral cortex. The pattern of distribution of anterogradely labelled profiles visualized with tetramethylbenzidine revealed that the caudal three-fourths of the lateral reticular nucleus received a large, topographically organized projection from the entire length of the contralateral spinal cord. The lateral part of the rostral half of the lateral reticular nucleus received a small projection from the contralateral red nucleus, the dorsal part of the middle third of the nucleus received a diffuse projection from the contralateral fastigial nucleus, and the extreme rostromedial part of the nucleus received a sparse projection from the contralateral cerebral cortex.

Dopaminergic innervation of substance P-containing striatal neurons by fetal nigral grafts: an ultrastructural double-labeling immunocytochemical study.

Evidence for survival and growth of fetal substantia nigra grafts in host striatum and partial reversal of behavioural and biochemical deficits in the host animal is well documented. Afferent synaptic connections arising from the graft and contacting host structures have also been reported; however, the properties of the neurons receiving this input is less clear. The purpose of this study was to determine if substance P-containing neostriatal neurons receive a dopaminergic input from nigral grafts.

Substance P immunoreactivity in the rat interpeduncular nucleus: synaptic interactions between substance P-positive profiles and choline acetyltransferase- or glutamate decarboxylase-immunoreactive structures.

The subnuclear and synaptic distribution of substance P immunoreactivity was examined in the rat interpeduncular nucleus at the light and electron microscope level. The nucleus possessed a prominent substance P-immunoreactive axonal plexus in the lateral and dorsomedial subnuclei, and in the dorsal cap of the rostral subnucleus. The density of substance P-immunoreactive axons in the remaining subnuclear divisions was sparse to moderate.

Efferent connections of the A1 noradrenergic cell group: a DBH immunohistochemical and PHA-L anterograde tracing study.

Immunohistochemical localization of the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) was employed to reveal the anatomical organization of the A1 noradrenergic cell group in the caudal ventrolateral medulla oblongata of the rat. Subsequently, the supraspinal efferent axonal projections of A1 were investigated with a view to elucidating the anatomical substrates underlying its postulated function in central fluid and cardiovascular homeostasis. Within the caudal medulla, DBH-positive/PNMT-negative (noradrenergic) neurons were observed extending bilaterally through the ventrolateral medullary reticular formation from upper cervical spinal cord levels to the level of the area postrema.

Simultaneous demonstration of choline acetyltransferase and glutamic acid decarboxylase immunoreactivity in the rat interpeduncular nucleus.

Double antigen immunohistochemistry was employed to simultaneously examine the distribution of choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) immunoreactivity in the rat interpeduncular nucleus (IPN) at the subnuclear and ultrastructural level. ChAT-immunoreactive axons of the fasciculus retroflexus (FR) innervated specific subnuclear divisions of the IPN that possessed GAD-immunoreactive somata and a high density of GAD-immunoreactive axons and terminals. At the ultrastructural level, each of the cholinoceptive subnuclei possessed a characteristic axodendritic synaptic contact.