Neuroscience
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Although the major routes of dopamine metabolism seem to be established, at least in terminal regions such as the striatum, it is important to search for previously unknown metabolites and to investigate the relevance of previously suggested minor alternative pathways. An urgent issue is to verify and quantify the transformation of dopamine to putative toxic species, another is to further explore metabolism of dopamine located in cell bodies/dendrites, e.g. in the substantia nigra. We have developed a new method in order to widen the search for alternative metabolites of dopamine. ⋯ The method was used to evaluate the possibility that cytochrome P450 2E1 is involved in the metabolism of dopamine in the substantia nigra. Significant changes in the radioactivity pattern were induced by inhibition of the enzyme but conclusions about whether cytochrome P450 2E1 is involved in the metabolism of dopamine or not requires further studies. The method can be used to study the metabolism of dopamine and can be extended, by using other radiolabelled precursors, also to evaluate metabolism of other transmitters, e.g. serotonin.
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Angiotensin II (Ang II) type 1 (AT1) receptors are prevalent in the sensory vagal complex including the nucleus tractus solitarii (NTS) and area postrema, each of which has been implicated in the central cardiovascular effects produced by Ang II. In rodents, these actions prominently involve the AT1A receptor. Thus, we examined the electron microscopic dual immunolabeling of antisera recognizing the AT1A receptor and Ang II to determine interactive sites in the sensory vagal complex of rat brain. ⋯ In the area postrema, AT1A receptor labeling also was detected in many non-neuronal cells including glia, capillary endothelial cells and perivascular fibroblasts that were less prevalent in the NTS. We conclude that in the rat sensory vagal complex, AT1A receptors are strategically positioned for involvement in modulation of the postsynaptic excitability and intracrine hormone-like effects of Ang II. In addition, these receptors have distributions consistent with diverse roles in regulation of transmitter release, regional blood flow and/or vascular permeability.
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Comparative Study
Immunohistochemical localization of myosin Va in the adult rat brain.
Brain myosin Va (MVa) is a molecular motor associated with plastic changes during development. MVa has previously been detected in the cell body and in dendrites of neuronal cells in culture, in cells of the guinea-pig cochlea, as well as in cerebellar cells. Adult Wistar rats (n=14), 250-300 g, were perfused with standard methods for immunohistochemistry, using a polyclonal, affinity-purified rabbit antibody against MVa tail domain. ⋯ The analysis of MVa and glial fibrillary acidic protein staining in adjacent brain sections demonstrated a clear-cut neuronal labeling rather than an astroglial staining. The studies presented here represent a comprehensive map of MVa regional distribution in the CNS of the adult rat and may contribute to the basic understanding of its role in brain function and plasticity, particularly in relationship to phenomena that involve molecular motors, such as neurite outgrowth, organelle transport and neurotransmitter-vesicle cycling. It is important to highlight that this is a pioneer immunohistochemical study on the distribution of MVa on the whole brain of adult rats, a first step toward the understanding of its function in the CNS.
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Comparative Study
Postnatal development and migration of cholecystokinin-immunoreactive interneurons in rat hippocampus.
The development of cholecystokinin-immunoreactive (CCK-IR) interneurons in the rat hippocampus was studied using immunocytochemical methods at the light and electron microscopic levels from early (P0-P8) to later postnatal (P12-P20) periods. The laminar distribution of CCK-IR cell bodies changed considerably during the studied period, which is suggested to be due to migration. CCK-IR cells appear to move from the molecular layer of the dentate gyrus to their final destination at the stratum granulosum/hilus border, and tend to concentrate in the distal third of stratum radiatum in CA1-3. ⋯ Thus, the innervation of CCK-IR interneurons apparently develops later than their output synapses, suggesting that they may be able to release transmitter before receiving any considerable excitatory drive. We conclude that CCK-IR cells represent one, if not the major, interneuron type that assists in the maturation of glutamatergic synapses (activation of N-methyl-D-aspartate receptors) via GABAergic depolarization of principal cell dendrites, and may contribute to the generation of giant depolarizing potentials. CCK-IR cells will change their function to perisomatic hyperpolarizing inhibition, as glutamatergic transmission in the network becomes operational.
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Comparative Study
Cholinergic interneurons of the nucleus accumbens and dorsal striatum are activated by the self-administration of cocaine.
The nucleus accumbens, a major component of the ventral striatum, and the dorsal striatum are primary targets of the mesolimbic dopamine pathway, which is a pathway that plays a critical role in reward and addiction. The shell compartment of the nucleus accumbens and the ventromedial striatum, in particular, receive extensive afferent projections from the ventral tegmental area, which is the major afferent source of the mesolimbic pathway [Prog Brain Res 99 (1993) 209; J Neurosci 7 (1987) 3915]. The present study focused on striatal cholinergic interneurons as potential key neurons involved in the neural basis of drug reinforcement. ⋯ In addition, activation was not found in the core compartment of the nucleus accumbens or the dorsolateral striatum, which receive extensive innervation from the substantia nigra and thus are more closely tied to the motor effects of the drug. In conclusion, cocaine-driven neuronal activation was specific to the shell compartment of the nucleus accumbens (R(2)=0.9365) and the ventromedial striatum (R(2)=0.9059). These findings demonstrate that cholinergic interneurons are involved in the initial stage of cocaine intake and that these neurons are located in areas of the nucleus accumbens and dorsal striatum that are more closely tied to the rewarding and hedonic effects rather than the motor effects of cocaine intake.