Opioid precursor gene expression in the human hypothalamus

Abstract

Using in situ hybridization histochemistry, we studied the distribution of neurons that express preproopiomelanocortin (pre-POMC), preprodynorphin (pre-PDYN), and preproenkephalin (pre-PENK) gene transcripts within the human hypothalamus and surrounding structures. Of the three opioid systems, pre-POMC neurons have the most restricted distribution. Pre-POMC cells are most numerous in the infundibular nucleus and retrochiasmatic area of the mediobasal hypothalamus; a few labeled cells are present within the boundaries of the ventromedial nucleus and infundibular stalk. Pre-POMC message was not found in the limited samples of structures adjacent to the hypothalamus. In contrast to neurons that express pre-POMC, neurons expressing pre-PDYN and pre-PENK are more widely represented throughout the hypothalamus and extrahypothalamic structures. However, pre-PDYN and pre-PENK cells differ from one another in distribution. Pre-PDYN message is especially abundant in neurons of the tuberal and mammillary regions, with a distinct population of labeled cells in the premammillary nucleus and dorsal posterior hypothalamus. Pre-PDYN gene expression also is found in neurons of the dorsomedial nucleus, ventromedial nucleus, caudal magnocellular portion of the paraventricular nucleus, dorsolateral supraoptic nucleus, tuberomammillary nucleus, caudal lateral hypothalamus, and retrochiasmatic area. In structures immediately adjacent to the hypothalamus, pre-PDYN neurons were observed in the caudate nucleus, putamen, cortical nucleus of the amygdala, and bed nucleus of the stria terminalis. Pre-PENK neurons occur in varying numbers in all hypothalamic nuclei except the mammillary bodies. The chiasmatic region is particularly rich in pre-PENK neurons, with the highest packing density in the intermediate nucleus [the intermediate nucleus (Braak and Braak [1987] Anat. Embryol. 176:315-330) has also been termed the sexually dimorphic nucleus of the preoptic area (SDA-POA; Swaab and Fliers [1985] Science 228:1112-1115) or the interstitial nucleus of the anterior hypothalamus 1 (Allen et al. [1989] J. Neurosci. 9:497-506)], dorsal suprachiasmatic nucleus, medial preoptic area, and rostral lateral hypothalamic area. Pre-PENK neurons are numerous in the infundibular nucleus, ventromedial nucleus, dorsomedial nucleus, caudal parvicellular portion of the paraventricular nucleus, tuberomammillary nucleus, lateral hypothalamus, and retrochiasmatic area. Only a few lightly labeled cells were found in the periphery of the supraoptic nucleus and lateral tuberal nucleus. In areas adjacent to the hypothalamus, cells that contain pre-PENK message occur in the nucleus basalis of Meynert, central nucleus of amygdala, bed nucleus of the stria terminalis, caudate nucleus, and putamen.(ABSTRACT TRUNCATED AT 400 WORDS)

Subjects with major depression or bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei of the amygdaloid complex

“…The complete study of the psychiatric brain specimens and respective controls Molecular Psychiatry was subsequently carried out under conditions using the 1.2-kb riboprobe. Consistent with previous studies, 1,23 at the amygdala levels examined, the highest prodynorphin hybridization signals were observed in the posterior cortical nucleus, amygdalohippocampal area, parvicellular division of the accessory basal (ABpc), and periamygdaloid cortex (except in the sulcal portion which showed low expression; Figures 2 and 3). Low to moderate expression levels were detected in the lateral nucleus, except in two individ- uals (one diagnosed with schizophrenia, the other with major depression) who showed an unusual prodynorphin mRNA expression pattern in the amygdala with very high hybridization signals in the lateral nuclei; no known demographic or toxicological information could account for this finding.…”

“…[20][21][22] The amgydaloid complex has one of the highest expressions of the prodynorphin gene in the human brain 1 with the prodynorphin mRNA expressed preferentially in superficial nuclei such as the cortical, amygdalohippocampal area (AHA), and periamygdaloid cortex in normal subjects. 1,23 There is also high prodynorphin mRNA expression in the accessory basal (AB) nucleus, the most medial of the deep amygdaloid nuceli. Considering that impairment of amygdaloid function can lead to dysfunction of the regulation of emotional states and that the dynorphin system has been linked with negative mood, the present study investigated the prodynorphin mRNA expression in the amygdaloid complex in individuals with mood disorders.…”

Preprotachykinin-A mRNA expression in the human and monkey brain: An in situ hybridization study

“…The mammillary body is an intricate component of the ' 'Papez circuit'' (Papez, 1937), which is hypothesized to be important for limbic function relevant for emotional expression, learning, and memory. Intense prodynorphin mRNA expression has been found within the human premammillary nuclei; however, unlike the PPT-A mRNA pattern, the prodynorphin gene is not expressed in the mammillary body (Hurd, 1996;Sukhov et al, 1995). Different roles in limbic function are expected for the premammillary nucleus and the mammillary body due to their distinct anatomic connectivity.…”

The expression and localization of ?-endorphin and �,?-opioid receptors in synovial tissues in patient with rheumatoid arthritis and osteoarthritis

“…According to human POMC cDNA, a 48-mer oligonucleotide encoding position 7106-7153 was synthesized for use as an antisense probe, 14,16,17 and the sequence of the oligonucleotide was 5Ј-GCCCACCGGCTTGCCCCAGCGGA AGTGCTCCATG GAGTAGGAGC GCTT-3Ј. In addition, the oligonucleotide with the reverse sequence was synthesized for use as a sense probe.…”

“…The tissues were fixed in 4% paraformaldehyde in phosphate-buffered solution (PBS) for 16-18 h at 4°C, and then immersed in 30% (w/v) sucrose in PBS containing 0.02% (v/v) diethylpyrocarbonate (Sigma, St. Louis, MO, USA) at 4°C for [16][17][18] h and frozen at Ϫ80°C until use. Frozen sections were then cut using a cryostat microtome at a thickness of 6 µm and mounted onto 3-aminopropylmethoxysilane-coated slides.…”