Microanatomical localization of dopamine receptor protein immunoreactivity in the rat cerebellar cortex
ABSTRACT Dopamine (DA) receptor subtype localization was investigated in rat cerebellar cortex using immunohistochemical techniques with antibodies raised against D1–D5 receptor protein. A faint D1 receptor protein immunoreactivity was developed in molecular and Purkinje neurons layers. D2 receptor protein immunoreactivity was found primarily in cerebellar white matter followed by molecular and granular layers and Purkinje neurons. Antibodies against D2S receptor protein were localized in molecular layer and to a lesser extent, in granular layer. A few Purkinje neurons displayed a faint D2S receptor protein immunoreactivity. D3 receptor protein immunoreactivity was observed primarily in molecular and in Purkinje neurons layers of lobules 9 and 10. A faint D3 receptor protein immunoreactivity was also localized in Purkinje neurons and to a lesser extent, in molecular and granular layers of cerebellar lobules 1–8. D4 receptor protein immunoreactivity was found in cerebellar white matter. A pale immunostaining was also visualized in molecular layer. D5 receptor protein immunoreactivity was localized primarily in molecular and Purkinje neurons layers and to a lesser extent, in granular layer and in white matter. The above results indicate that rat cerebellar cortex expresses the DA receptor subtypes so far identified. Purkinje neurons, which are the only efferent neurons of cerebellum, are richest in DA receptor protein immunoreactivity. This suggests that dopaminergic neurotransmission may modulate efferent inputs from cerebellum. The localization of the majority of D2 and D4 and of a faint D5 protein receptor immunoreactivity in cerebellar white matter suggests that these receptors may be presynaptic and transported axonally.
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ABSTRACT: Thyrotropin-releasing hormone (TRH) was originally isolated from the hypothalamus. Besides controlling the secretion of TSH from the anterior pituitary, this tripeptide is widely distributed in the central nervous system and regarded as a neurotransmitter or modulator of neuronal activities in extrahypothalamic regions, including the cerebellum. TRH has an important role in the regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation. TRH controls energy homeostasis mainly through its hypophysiotropic actions to regulate circulating thyroid hormone levels. Recent investigations have revealed that TRH production is regulated directly at the transcriptional level by leptin, one of the adipocytokines that plays a critical role in feeding and energy expenditure. The improvement of ataxic gait is one of the important pharmacological properties of TRH. In the cerebellum, cyclic GMP has been shown to be involved in the effects of TRH. TRH knockout mice show characteristic phenotypes of tertiary hypothyroidism, but no morphological changes in their cerebellum. Further analysis of TRH-deficient mice revealed that the expression of PFTAIRE protein kinase1 (PFTK1), a cdc2-related kinase, in the cerebellum was induced by TRH through the NO-cGMP pathway. The antiataxic effect of TRH and TRH analogs has been investigated in rolling mouse Nagoya (RMN) or 3-acetylpyridine treated rats, which are regarded as a model of human cerebellar degenerative disease. TRH and TRH analogs are promising clinical therapeutic agents for inducing arousal effects, amelioration of mental depression, and improvement of cerebellar ataxia.The Cerebellum 05/2008; 7(1):84-95. · 2.60 Impact Factor
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ABSTRACT: Neurotrophins (NTs) promote survival and differentiation of central and peripheral neurons, and display several activities also in non-neuronal cells. Human lungs synthesize and release NTs, which are probably involved in the pathophysiology of pulmonary disturbances. In this article the expression and anatomic localization of nerve growth factor, brain-derived neurotrophic factor, and NT-3 and of corresponding high-affinity receptors TrkA, TrkB (full-length and truncated [TR-] isoforms), TrkC, and of the low-affinity p75 receptor, were assessed in surgical samples from adult human lung by reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. NTs and their cognate receptor mRNA and protein transcripts were detected by reverse transcriptase-polymerase chain reaction and immunoblotting, respectively, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA and corresponding protein transcripts being the most expressed. High levels of TrkB-[TR-] mRNA and of its protein transcript were also demonstrated, whereas a low expression of p75 mRNA and of corresponding protein transcript were found. Microanatomic analysis of immunohistochemical study revealed that bronchial epithelial cells were immunoreactive for different NTs, with a higher intensity of BDNF immune staining compared with other NTs, but did not express NT receptor immunoreactivity. Alveolar cells were immunoreactive for TrkA and TrkC receptor protein, but did not display immunoreactivity for NTs or other receptors investigated. Gland cells expressed NT and high-affinity NT receptor immunoreactivity, but not p75 receptor immunoreactivity. NT and low-affinity receptor immunoreactivity was observed within neurons and satellite cells of parasympathetic ganglia as well as in nerve fiber-like structures supplying the bronchopulmonary tree. An obvious immunoreactivity for NTs and NT receptor protein was also observed in intrapulmonary branches of pulmonary artery. Pulmonary lymphocytes and macrophages express nerve growth factor and high-affinity NT receptor immunoreactivity. The role of NTs in non-neuronal tissue including lung has not been clarified yet. The widespread expression of NTs and their receptors in different components of the lung suggests that these factors may contribute to regulate cell function in human lung.American Journal of Respiratory Cell and Molecular Biology 02/2004; 30(1):12-9. · 4.15 Impact Factor
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ABSTRACT: Dopamine D1-D5 receptor protein immunoreactivity and tyrosine hydroxylase (TH) immunoreactivity were investigated on the mesenteric arterial tree by immunohistochemistry. The density of various dopamine receptors and TH immunoreactivity was compared between young (6-month-old), adult (15-month-old) and senescent (24-month-old) Fischer 344 rats by computer-assisted microdensitometry. The dopamine D1-like (D1 and D5) receptors were localized on the tunica media of different sized mesenteric artery branches. The D2-like (D2, D3 and D4) receptors as well as TH immunoreactivity were localized only on the adventitia-media transitional zone of mesenteric arterial tree. Expression of the D1 and D5 receptors was decreased in both adult and senescent rats compared to the young rats, suggesting an age-related decline in these receptors. Of the D2-like receptors, the expression of the D2 receptor was decreased as a function of age, while the D3 receptor was unchanged in the senescent rats compared to the young rats. Expression of the D4 receptor was increased in adult, but was unchanged in the senescent rats compared to young animals. TH immunoreactivity was increased as a function of age. The above data suggest that reduction in the D1, D2 and D5 receptor expression may contribute to the deficiency in the dopamine-mediated vasorelaxation and hence blood flow in the mesenteric vascular tree in aging. The different sensitivity to aging of sympathetic neuroeffector junctions labeled by TH and of dopamine D2-like receptors that are known to be prejunctional, suggests that age-related changes of dopamine receptor expression in the mesenteric vasculature reflect more complicated mechanisms than simple up- or down-regulation phenomena.Mechanisms of Ageing and Development 04/2002; 123(5):537-46. · 3.26 Impact Factor