Isolation, characterization, and application of monoclonal antibodies to rat tyrosine hydroxylase

Kwan, Sau-Wah; Patel, Nutan T.; Vulliet, Philip R; Hall, Frederick L.; Denney, R M; Shen, Rong; Westlund, Karin N.; Abell, C. W.

doi:10.1002/jnr.490230311

Cited by 4 publications

(1 citation statement)

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“…All the TH-IR cells were red due to excitation of CY-3 fluorescent dye. Densely packed medium-sized TH-IR neurons were distributed in agreement with the description of previous immunohistochemical detection studies of TH (Pickel et al, 1975) or DA (Kwan et al, 1989;Dabadie et al, 1990;Moons et al, 1994) or chemical staining of monoaminecontaining neurons with glyoxylic acid (Lindvall et Bjorklund, 1974). Cells stained by the anti-TH antibody were principally located within the SNpc, where they were spread densely, but only a few positive cells were present in the SNpr.…”

Section: Studies In the Substantia Nigrasupporting

confidence: 65%

Immunohistochemical studies of the localization of neurons containing the enzyme that synthesizes dopamine, GABA, or ?-hydroxybutyrate in the rat substantia nigra and striatum

et al. 2000

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gamma-Hydroxybutyrate (GHB) is an endogenous metabolite of gamma-aminobutyric acid (GABA), which is synthesized in the neuronal compartment of the central nervous system. This substance possesses several properties that support its role as a neurotransmitter/neuromodulator in brain. In particular, it is synthesized by a specific pathway that transforms GABA into succinic semialdehyde via GABA-T activity; then succinic semialdehyde is converted into GHB by a specific succinic semialdehyde reductase (SSR). The last enzyme is considered as a marker for neurons that synthesize GHB. This compound binds in brain to receptors whose distribution, ontogenesis, kinetics, and pharmacology are specific. Endogenous GHB, but also GHB exogenously administered to rats, participate in the regulation of dopaminergic activity of the nigrostriatal pathway. To investigate the distribution of GHB neurons in this pathway and the anatomic relationships between dopaminergic and GHB neurons, immunocytochemical identification of dopamine, GABA, and GHB neurons was carried out in the substantia nigra and striatum of the rat. The following markers for these neurons were used: anti-tyrosine hydroxylase (TH) antibodies for dopamine neurons, anti-glutamate decarboxylase (GAD) antibodies for GABA neurons, and anti-succinic semialdehyde reductase (SSR) antibodies for GHB neurons. GABA neurons were studied because GAD and SSR co-exist frequently in the same neuron, and GABA alone also exerts its own regulatory effects on dopaminergic neurons. This study reveals the co-existence of GAD/SSR and GAD/SSR/TH in numerous neurons of the substantia nigra. However, some neurons appear to be only GAD or SSR positive. In the striatum, TH-positive terminals surround many GHB neurons. GAD innervation is abundant in close contact with unlabeled neurons in the caudate-putamen, whereas distinct SSR-positive punctuates are also present. The existence of SSR-reactive synapses and neurons was confirmed in the striatum at the electron microscopic level. On the basis of these results, a clear anatomo-functional relationship between GHB and dopamine networks cannot be defined; however, we propose the modulation by GHB of striatal intrinsic neurons that could then interfere with the presynaptic control of dopaminergic activity.

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