Cephalopod research remains limited by the inability to culture species under laboratory conditions for multiple generations to provide continuous access to animals at all stages of the life cycle. ...Here, we describe a multi-generational laboratory culture system for two emerging cephalopod models: the hummingbird or Berry’s bobtail squid,
Euprymna berryi
Sasaki, 1929, and Morse’s bobtail squid,
Euprymna morsei
Verrill, 1881, which are primarily found off mainland Japan.
E. berryi
wild adults were spawned and raised to the third filial generation, and
E. morsei
wild adults were spawned and raised to the second filial generation in a closed system at 20°C. We report growth and survivorship data for a cohort of 30 individuals across the first generation raised in captivity.
E. berryi
and
E. morsei
grew exponentially during the first 90 and 60 days post-hatching, respectively. Survivorship at the first spawning event for
E. berryi
and
E. morsei
was 90% and 77%.
E. berryi
and
E. morsei
females spawned after days 112 and 71 days post-hatching, respectively. We describe the life history of each species and how to distinguish sexes. We discuss the challenges of cephalopod culture and how culturing these species address those problems.
► Tipepidine produces an antidepressant like effect in the forced swimming test. ► The effect of tipepidine may be produced via dopamine D
1 and alpha2 adrenoceptor. ► The properties of the effect ...may be different from those of known antidepressants.
We previously reported that the centrally acting non-narcotic antitussive, tipepidine, produces a novel antidepressant-like effect in the forced swimming test in rats, but the mechanism of the antidepressant-like effect of tipepidine is not clear. We investigated the pharmacological mechanism of the antidepressant-like effect of tipepidine in the forced swimming test in rats. A catecholamine-depleting agent, alpha-methyl-
p-tyrosine (AMPT; 300
mg/kg, s.c.), was given 6
h before the first injection and with the last injection of tipepidine (40
mg/kg, i.p.). A serotonin (5-HT)-depleting agent,
p-chlorophenylalanine (PCPA; 350
mg/kg, i.p.), was given 72
h and 48
h before the pretest session. The dopamine D
1 receptor antagonist, SCH23390 (0.02
mg/kg, s.c.) was given 15
min before each of the three injections of tipepidine. The dopamine D
2 receptor antagonist raclopride (0.2
mg/kg, s.c.), the alpha 1 adrenoceptor antagonist prazosin (1
mg/kg, i.p.), the alpha 2 adrenoceptor antagonist yohimbine (2
mg/kg, i.p.) and the beta adrenoceptor antagonist propranolol (2
mg/kg, i.p.) were given 30
min before each of the three injections of tipepidine. AMPT, but not PCPA, significantly inhibited the immobility time-reducing effect of tipepidine in the forced swimming test. Furthermore, the effect of tipepidine was significantly inhibited by SCH23390 and yohimbine. However, raclopride, prazosin, and propranolol failed to block the effect of tipepidine. The results suggest that the antidepressant-like effect of tipepidine in the forced swimming test may be due at least in part to the effects of dopamine and noradrenaline released at the dopamine D
1 receptor and alpha 2 adrenoceptor, respectively.
Abstract We previously reported that tipepidine, a centrally acting non-narcotic antitussive, has an antidepressant-like effect in normal and imipramine treatment-resistant depression model rats. ...Recently, mapping the induction of c-fos-like immunoreactivity (FLI) in the rat brain showed FLI-positive neurons in several brain areas after acute administration of different classes of antidepressants. Here, the effect of a single injection of an antidepressive dose of tipepidine on FLI was studied in seven areas of the rat brain including the central nucleus of the amygdala (CeA) and the nucleus accumbens (NAc). Desipramine was also used for comparison. Rats were anesthetized and perfused 2 h after injection with tipepidine (20 and 40 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), or saline. Then, immunostaining of FLI-positive neurons in brain slices was performed with conventional methods. A single injection of tipepidine increased FLI-positive neurons in the CeA, similar to preexisting antidepressants, and induced the characteristic pattern of an increase in FLI-positive neurons in six other brain areas including the NAc, an effect that was different from other antidepressants. In addition, a single injection of desipramine (10 mg/kg) or tipepidine (20 mg/kg) decreased the immobility time in the forced swimming test to a similar extent. The results obtained from the previous behavioral study and the current immunohistochemical study suggest that tipepidine may be a novel antidepressant.
Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because ...pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40
mg/kg i.p. significantly reduced immobility. At 40
mg/kg i.p., it increased climbing behavior. Even at 40
mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect.
Several antidepressants have been used to treat severe pain in clinics. Recently, we reported that the centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an ...antidepressant-like effect in the forced swimming test, although the mechanism of action appears to be quite different from that of known antidepressants. In the present study, we investigated whether a combination of tipepidine and carbamazepine acts synergistically to induce an antinociceptive effect in the acetic acid-induced writhing test in mice. Prior to studying the combination of tipepidine and carbamazepine, the analgesic action of tipepidine alone was also examined in mice. Tipepidine at 5–40mg/kg i.p. significantly reduced the number of writhes induced by acetic acid in mice. Carbamazepine at 20mg/kg i.p. also significantly reduced the writhing reaction. Furthermore, co-administration of carbamazepine (5 and 10mg/kg, i.p.) and tipepidine (2.5mg/kg i.p.) significantly decreased the number of writhes induced by acetic acid. This finding suggests that a combination of carbamazepine and tipepidine may be a new strategy for the treatment of neuropathic pain such as what occurs in trigeminal neuralgia, because the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic efficacy by microsomal enzyme induction.
Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens ...including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.
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•scRNA-seq displayed genetically defined characteristics of hereditary kidney cancer•scRNA-seq revealed unique tissue microenvironment of each hereditary kidney cancer•BHD-associated kidney cancer showed transcriptomic intratumor heterogeneity (tITH)•BHD-associated kidney cancer showed intercalated cell characteristics driven by FOXI1
Oncology; Microenvironment; Human specimen; Cancer systems biology; Cancer;
