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Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus.
Wiater MF, Mukherjee S, Li AJ, Dinh TT, Rooney EM, Simasko SM, Ritter S (2011) Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus. Am J Physiol Regul Integr Comp Physiol 301(5):R1569-R1583. doi: 10.1152/ajpregu.00168.2011 PMID: 21880863
Summary: Feeding and sleep/wake states interact rhythmically across the circadian cycle. It is suspected that the mediobasal hypothalamic area (MBH) is the site where these rhythms are integrated. The authors administered bilateral 24-ng injections of NPY-SAP (Cat. #IT-28) into the arcuate nucleus in order to eliminate NPY receptor-expressing neurons in the MBH of rats. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate that these neurons are required for the interaction of feeding and sleep/wake timing.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Neural and hormonal control of food hoarding.
Bartness TJ, Keen-Rhinehart E, Dailey MJ, Teubner BJ (2011) Neural and hormonal control of food hoarding. Am J Physiol Regul Integr Comp Physiol 301(3):R641-R655. doi: 10.1152/ajpregu.00137.2011
Summary: Hoarding of food is a commonly found behavior in humans and animals. This review discusses the neuronal and hormonal processes involved in the control of food hoarding. Several aspects of food hoarding are examined, including the role of food deprivation, environment, levels of hormones like leptin, ghrelin, and levels of peptides such as cholecystokinin. One experiment discussed injected NPY-SAP (Cat. #IT-28) into the arcuate nucleus of rats, which changed food hoarding responses to deprivation.
Related Products: NPY-SAP (Cat. #IT-28)
The arcuate nucleus of the hypothalamus controls the circadian distribution of sleep and feeding
Wiater MF, Mukherjee S, Dinh TT, Rooney E, Li A-J, Simasko SM, Ritter S (2010) The arcuate nucleus of the hypothalamus controls the circadian distribution of sleep and feeding. Neuroscience 2010 Abstracts 648.16/H17. Society for Neuroscience, San Diego, CA.
Summary: Integration of daily sleep and feeding rhythms is incompletely understood. We examined the role of the hypothalamic arcuate nucleus (Arc) in these processes using Arc microinjections of the targeted toxin, NPY-saporin (NPY-SAP), or control blank-saporin (B-SAP). NPY-sap targets and destroys NPY receptor-expressing neurons. We monitored 24 hr feeding over a 30-day period beginning 2 wks after the Arc injections, and used EEG recordings to assign vigilance states. Vigilance was divided into rapid-eye movement sleep (REMS), non-REMS (NREMS) and wake. NPY-SAP lesioned rats were hyperphagic , consuming up to 225% of pre-injection baseline. They rapidly became obese. While in the sleep-monitoring chambers, their body weight change per week ranged from 56 ± 9 g to 40.5 ± 4.5g, compared to 6 ± 0.4 g/wk for B-SAP rats. Their circadian pattern of food intake was severely disrupted, such that intake in light and dark periods were approximately equal (43% of their total intake was consumed in the light period vs. 25% in B-SAP controls). Sleep patterns were also significantly disrupted in the NPY-SAP animals. The occurrence of rapid eye movement sleep (REMS) was inverted in phase, occurring mainly at night, rather than during the day. NonREMS was distributed equally across day and night, instead of occurring predominantly during the day. However, 24-hr total REMS and NREMS time was normal. B-SAP controls had normal sleep patterns, with NREMS and REMS occurring predominantly in the light phase. To determine if the change in sleep pattern was due to the change in feeding patterns, we restricted access to food to the dark period for 4 days. NPY-SAP treated animals doubled their food intake in the dark period. However, sleep patterns were not changed compared to the ad libitum feeding period in either NPY-SAP or B-SAP rats. After 7 days of ad libitum feeding, we restricted food access to the light period for 4 days. Again, NPY-SAP animals doubled their intake during the feeding period, this time during the light phase, and sleep patterns were not changed in either group by the restricted feeding. By 100 days post-lesion, the NPY-sap animals were still obese, but the patterning and amount of their food intake were becoming similar to controls. However, when evaluated again, sleep patterns were still altered to the same degree as observed early post-lesion. These results confirm the importance of NPY-receptive Arc neurons in controlling food intake. They also reveal an unexpected role for the Arc in the timing of both NREMS and REMS that appears to be independent of the patterning of food intake.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Neuropeptide receptor co-expression in superficial dorsal horn: Effects of galanin-saporin, neuropeptide y-saporin and dermorphin-saporin
Lemons LL, Chatterjee K, Wiley RG (2010) Neuropeptide receptor co-expression in superficial dorsal horn: Effects of galanin-saporin, neuropeptide y-saporin and dermorphin-saporin. Neuroscience 2010 Abstracts 585.5/XX19. Society for Neuroscience, San Diego, CA.
Summary: We have previously shown that the role of specific neurons in behavioral processes can be fruitfully studied using targeted toxins. Toxins composed of a targeting neuropeptide coupled to the ribosomal-inactivating toxin, saporin, are used to selectively destroy superficial dorsal horn neurons expressing the cognate peptide receptors followed by assessment of changes in pain behavior. In the present study, we sought to compare the anatomic effects of three closely related targeted toxins, each with different nocifensive behavioral effects. Rats were given single lumbar intrathecal injections of either galanin-saporin (Gal-SAP), neuropeptide Y-saporin (NPY-SAP), or dermorphin-saporin (Derm-SAP). Lumbar spinal cord sections from each rat were stained for each of the three receptors, GalR-1, Y1R and MOR (mu opiate) using standard immunoperoxidase technique. Each toxin produced a significant decrease in staining for its cognate receptor. Gal-SAP animals showed no change in either MOR or Y1R staining. NPY-SAP rats showed decreased staining for both GalR1 and MOR, and Derm-SAP rats were assessed for changes in expression of GalR1 and Y1R. These findings suggest overlaps between the populations of neurons that express the GalR1, Y1R, and MOR. Specifically, Y1R-expressing neurons also express GalR1 and MOR, probably by separate subpopulations of Y1R neurons. The results also suggest either that Gal-SAP only kills neurons that do not express either of the other two receptors, or some of the observed loss of receptors after NPY-SAP is due to secondary (transsynaptic) effects. Double- and triple-label fluorescent immunohistochemistry will be used to directly visualize receptor co-expression patterns and targeted toxin effects. These results will be valuable in interpreting the unique nocifensive behavioral effects of each of these targeted toxins.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Galanin-SAP (Cat. #IT-34), NPY-SAP (Cat. #IT-28)
Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice.
Lyons AM, Thiele TE (2010) Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice. Peptides 31(12):2193-2199. doi: 10.1016/j.peptides.2010.09.009
Summary: Neuropeptide Y (NPY) in the hypothalamus is known to modulate feeding behavior. In this work the authors used bilateral 48 ng injections of NPY-SAP (Cat. #IT-28) into the central amygdala or basomedial hypothalamus (BMH) of rats to investigate the role of NPY in anxiety. Blank-SAP (Cat. #IT-21) was used as a control. Injections into the amygdala increased anxiety-like behavior, while injections into the BMH reduced anxiety-like behavior. BMH injections also initiated an increase of NPY-1 receptor expression in the basolateral nuclei of the amygdala.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding.
Dailey MJ, Bartness TJ (2010) Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding. Brain Res 1323:94-108. doi: 10.1016/j.brainres.2010.01.078
Summary: While some aspects of food intake are understood, mechanisms controlling hoarding of food have not been identified. This work investigates the role of NPY in the arcuate nucleus (Arc) in hoarding. Siberian hamsters received 48 ng injections of NPY-SAP (Cat. #IT-28) into the Arc; blank-SAP (Cat. #IT-21) was used as a control. In lesioned animals food deprivation-induced hoarding was increased 100%, but baseline foraging and food hoarding was unchanged.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Leptin-saporin injection into the arcuate nucleus lesions NPY/AGRP and POMC neurons and produces hyperphagia, obesity and changes in diurnal feeding patterns in rats
Li A-J, Wang Q, Dinh TT, Ritter S (2009) Leptin-saporin injection into the arcuate nucleus lesions NPY/AGRP and POMC neurons and produces hyperphagia, obesity and changes in diurnal feeding patterns in rats. Neuroscience 2009 Abstracts 374.5/EE116. Society for Neuroscience, Chicago, IL.
Summary: Leptin-saporin (Lep-SAP), a conjugate of leptin with a ribosomal inactivating toxin, saporin (Advanced Targeting Systems), is a novel toxin designed to destroy leptin receptor-expressing cells selectively in vitro. However, its lesioning properties in vivo are currently unknown. Here, we injected Lep-SAP into the arcuate nucleus (Arc), to examine its effects on feeding behavior and on leptin receptor-expressing NPY/AGRP and POMC neurons in this area. Immunohistochemical studies showed unilateral injection of Lep-SAP into the Arc dramatically reduced numbers of NPY-Y1- and α-MSH- positive neurons compared to the contralateral side injected with SAP control. Real-time PCR revealed only 11-21% of Agrp and Pomc expression remaining in the Arc after Lep-SAP injection into this region. Rats injected bilaterally with Lep-SAP were unresponsive to central leptin administration and showed dramatic increases in feeding, body weight and light-phase feeding, compared pre-injection baseline. Two weeks after injection, total daily feeding was increased by 75%, light phase feeding by 359% and dark phase feeding by 33%. Control SAP injections did not produce these changes. Clock gene expression in homogenates of whole hypothalamus and liver were quantified at ZT 5-7. Bmal1 expression in hypothalamus and liver of Lep-SAP rats was decreased, while hepatic Per1 expression was increased compared to control. Results demonstrate that Lep-SAP effectively lesions Arc leptin receptor-expressing NPY/AGRP and POMC neurons in vivo, and that rats with this lesion are hyperphagic and obese, possibly due to enhanced hunger drive, lack of responsiveness to leptin and/or changes in circadian control of feeding behavior.
Related Products: NPY-SAP (Cat. #IT-28), Leptin-SAP (Cat. #IT-47)
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Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin.
Wiley RG, Lemons LL, Kline IV RH (2009) Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147. doi: 10.1016/j.neuroscience.2008.12.017
Summary: This work examines the effect of lumbar intrathecal administration of NPY-SAP (Cat. #IT-28), and the role of Y1 NPY receptor-expressing neurons (Y1R) in response to thermal and chemical stimulation. Rats received 500 ng or 750 ng intrathecal injections of NPY-SAP. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed a specific loss of Y1R in the dorsal horn, as well as reduced nocifensive reflex responses.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Analysis of inhibitory phase of formalin test: Effects of specific neural lesions
Wiley RG, Moore SA, Kline IV RH (2008) Analysis of inhibitory phase of formalin test: Effects of specific neural lesions. Neuroscience 2008 Abstracts 772.4/MM19. Society for Neuroscience, Washington, DC.
Summary: The formalin test has been widely used as a model of persistent pain. The 90 mins of formalin-induced nocifensive responding can be divided into two phases (phase 1, first ~10 mins; phase 2, last ~60 mins) separated by a period of reduced responding (interphase, IP), that has received relatively little attention. Behavioral inhibition during the IP of the formalin test has been associated with electrophysiological evidence of inhibition of dorsal horn nociceptive neurons (Henry et al, Pain, 82:57, 1999), probably due, at least in part, to local spinal mechanisms. Behavioral inhibition during IP has been shown to be enhanced by morphine and suppressed by naloxone. In the present study, we sought to determine the effect of selective depletion of specific dorsal horn interneurons known to be involved in nociception, i.e. neurons expressing NPY1R, GalR1 or MOR, or selective destruction of cerebral noradrenergic neurons or spinal cord projecting 5-HT neurons on formalin-induced nociceptive behavior, with particular attention to IP. Type-selective lesions were produced by lumbar intrathecal injection of NPY-saporin, galanin-saporin or dermorphin-saporin, respectively. Cerebral noradrenergic neurons and spinally projecting 5-HT neurons were destroyed using the immunotoxins, anti-DBH-saporin (intracerebroventricular) or anti-SERT-saporin (lumbar intrathecal), respectively. Partial loss of dorsal horn interneurons expressing NPY1R or GalR1 decreased nocifensive responding during IP and phase 2 of the formalin test, while partial loss of MOR-expressing dorsal horn interneurons increased nocifensive responding during IP and during phase 2. Both antiDBH-sap and antiSERT-sap decreased responding during IP, without effects on either phase 1 or 2. These results suggest that the apparent anti-nociception during IP and phase 2 produced by loss of NPY1R- and GalR1-expressing dorsal horn neurons is due to increased inhibition over excitation/facilitation of nociceptive projection neurons, whereas depletion of MOR-expressing interneurons produces the opposite effect. The apparent enhanced nociception during IP, but not phase I and II, produced by anti-DBH-sap and anti-SERT-sap suggests that these neural systems serve to enhance the excitability of nociceptive projection neurons during the formalin IP. Electrophysiologic and pharmacologic studies of formalin IP in selectively lesioned animals combined with the above behavioral findings may reveal new insights into endogenous modulation of nocifensive motor responses and/or nociception.
Related Products: NPY-SAP (Cat. #IT-28), Anti-SERT-SAP (Cat. #IT-23), Galanin-SAP (Cat. #IT-34), Anti-DBH-SAP (Cat. #IT-03), Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Hyperphagia and obesity produced by arcuate injection of NPY-saporin do not require upregulation of lateral hypothalamic orexigenic peptide genes.
Li AJ, Dinh TT, Ritter S (2008) Hyperphagia and obesity produced by arcuate injection of NPY-saporin do not require upregulation of lateral hypothalamic orexigenic peptide genes. Peptides 29(10):1732-1739. doi: 10.1016/j.peptides.2008.05.026
Summary: It has already been shown that lesioning NPY receptor-expressing cells in the arcuate nucleus (Arc) and basomedial hypothalamus produces obesity in rats. The authors examined the contribution of orexigenic peptides, orexins, and melanocortin-concentrating hormone to the lesion effects. Rats received bilateral 24 ng injections of NPY-SAP (Cat. #IT-28) into the dorsal border of the Arc. Blank-SAP (Cat. #IT-21) was used as a control. The data suggest that obesity produced by NPY-SAP lesion is different than dietary obesity or obesity associated with leptin or leptin receptor deficiency.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)