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Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats
Iqbal Z, Lei Z, Ramkrishnan AS, Liu S, Hasan M, Akter M, Lam YY, Li Y (2023) Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats. Commun Biol 6:10. doi: 10.1038/s42003-022-04405-6 PMID: 36604595
Objective: To identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC).
Summary: The findings suggest that projection-specific adrenergic astrocytic signaling in ACC is integral to system-wide neuromodulation in response to visceral stimuli and plays a key role in mediating pain-related aversion consolidation and memory formation.
Usage: 0.25 ug of Anti-DBH-SAP (1 μg/μl) was injected into each hemisphere of locus coeruleus (LC).
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Spinal GABAergic disinhibition allows microglial activation mediating the development of nociplastic pain in male mice
McDonough KE, Hammond R, Wang J, Tierney J, Hankerd K, Chung JM, La JH (2023) Spinal GABAergic disinhibition allows microglial activation mediating the development of nociplastic pain in male mice. Brain Behav Immun 107:215-224. doi: 10.1016/j.bbi.2022.10.013 PMID: 36273650
Objective: To investigate whether spinal microglia drive the transition from acute injury-induced pain to nociplastic pain in males, and if so, how they are activated by normally innocuous stimulation after peripheral injury.
Summary: The results demonstrate that in males, the transition from acute injury-induced pain to nociplastic pain is driven by spinal microglia causing neuroinflammation and that peripheral injury-induced spinal GABAergic disinhibition is pivotal for normally innocuous stimulation to activate spinal microglia.
Usage: Investigating the mechanisms of transition from acute to nociplastic pain, mice received a single intrathecal injection of unconjugated saporin (PR-01) or Mac-1-saporin (IT-06, 8.85 μM, 5 μL)
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease
Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326
Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.
Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)
The impact of advanced age on morphine anti-hyperalgesia and the role of mu opioid receptor signaling in the periaqueductal gray of male and female rats
Fullerton E (2022) The impact of advanced age on morphine anti-hyperalgesia and the role of mu opioid receptor signaling in the periaqueductal gray of male and female rats. Georgia State University Thesis. doi: 10.57709/30509896
Objective: To investigate the impact of advanced age on the antihyperalgesic effect of morphine, as well as its association with changes in μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG) in both male and female rats.
Summary: This study examined the effects of advanced age on the antihyperalgesic properties of morphine and its relationship with mu-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG). The findings revealed that advanced age attenuated the antihyperalgesic effect of morphine, accompanied by a decrease in mu-opioid receptor expression and binding in the PAG of both male and female rats, suggesting age-related alterations in opioid signaling that may contribute to reduced analgesic efficacy in older individuals.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis
Maunze B (2022) Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis. Marquette University Dissertations 1212. Thesis.
Objective: To determine the endogenous role of pituitary adenylate cyclase activating polypeptide (PACAP) in affecting the ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the Type I PAC1 receptor (PAC1R).
Summary: VMN cells expressing PAC1 receptors in Male Sprague Dawley rats were knocked down via injection of Saporin or PACAP-SAP and trafficking also pharmacologically inhibited. This increased meal sizes, reduced total number of meals, and induced body weight gain. PACAP signaling replicates the effects of leptin administration in the VMN and appears to enable leptin regulation of energy homeostasis. Co-immunoprecipitation was used to show that VMN PAC1 and leptin receptors are found in the same cell, and they form an immunocomplex. Inhibiting downstream effectors of PACAP signaling, such as PKA and PKC, enhanced or prevented leptin signaling respectively. The current findings revealed that endogenous PACAP signaling in the VMN has a potent regulatory influence over both energy intake in the form of feeding, and energy output via thermogenesis and locomotor activity. Moreover, PACAP actions in the VMN share nearly identical secondary effects as with leptin administration in the same brain region suggesting that these two neuropeptides could functionally intersect.
Related Products: PACAP-SAP (Cat. #IT-84)
Angiotensin II increases the firing activity of pallidal neurons and participates in motor control in rats.
Liu H, Xue Y, Chen L (2022) Angiotensin II increases the firing activity of pallidal neurons and participates in motor control in rats. Metab Brain Dis 38:573-587. doi: 10.1007/s11011-022-01127-w PMID: 36454502
Objective: To investigate the functions of angiotensin II (Ang II)/angiotensin subtype 1 receptor (AT1R) on the globus pallidus neurons of both normal and Parkinsonian rats.
Summary: The authors conclude that pallidal Ang II/AT1R alleviated Parkinsonian motor deficits by activating globus pallidus neurons. This provides a rationale for further investigations into the potential of Ang II for treating motor disorders originating from the basal ganglia.
Usage: Coronal Sections (40 μm) containing the globus pallidus were blocked with 5% BSA and 0.3% Triton X-100 in PBS for 45 min and subsequently incubated with AT1R antibody (AB-N27AP) for 48 h at 4°.
Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)
Keratinocyte growth factor stimulates growth of p75+ neural crest lineage cells during middle ear cholesteatoma formation in mice
Yamamoto-Fukuda T, Akiyama N, Tatsumi N, Okabe M, Kojima H (2022) Keratinocyte growth factor stimulates growth of p75+ neural crest lineage cells during middle ear cholesteatoma formation in mice. Am J Pathol 192(11):1573-1591. doi: 10.1016/j.ajpath.2022.07.010 PMID: 36210210
Objective: To identify the role of neural crest (NC) lineage epithelial cells during cholesteatoma formation and to detect specific cell markers to identify these NC lineage epithelial cells in human cholesteatoma tissues.
Summary: Cholesteatoma is a pathologic condition associated with otitis media and is a gradually destructive epithelial tumor within the middle ear and temporal bone. NC lineage epithelium controls the homeostasis of the middle ear and plays a role in repairing otitis media. Keratinocyte growth factor (KGF) stimulates epithelial cell growth and is associated with the recurrence of cholesteatomas. Injections of the immunotoxin mu p75-SAP (Cat. #IT-16) into the cholesteatoma tissue eliminated p75-postitive NC cells and diminished the cholesteatoma. This helped demonstrate that NC lineages are the cellular origin of cholesteatoma and that p75 transcription under KGF is required for the development of cholesteatoma. Controlling p75 signaling may reduce the proliferation of NC cells and could represent a new therapeutic target for cholesteatoma.
Usage: 10 uL mu-p75-SAP (0.2 or 0.6 mg/mL) was injected into the cholesteatoma region or tympanic membrane.
Related Products: mu p75-SAP (Cat. #IT-16)
GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein
Hoffman S, Alvares D, Adeli K (2022) GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein. Mol Metab 65:101590. doi: 10.1016/j.molmet.2022.101590 PMID: 36067913
Objective: To examine the effect of vagal GLP-1 signaling on intestinal fat absorption and lipoprotein production.
Summary: Selective deafferentation of GLP-1R-containing nodose neurons with GLP-1R (Exenatide)-SAP caused significant increases in postprandial (but not fasting) plasma TG, plasma cholesterol, and TRL TG following an olive oil gavage. Over a 2-week period, increased food consumption and elevated liver lipids were also observed.
Usage: GLP-1R-SAP or Blank-SAP was administered to Syrian golden hamsters (bilateral nodose ganglia; 1 µg/1 µl).
Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-SAP (Cat. #IT-21)
Norepinephrine innervation of the supraoptic nucleus contributes to increased copeptin and dilutional hyponatremia in male rats
Aikins AO, Little JT, Rybalchenko N, Cunningham JT (2022) Norepinephrine innervation of the supraoptic nucleus contributes to increased copeptin and dilutional hyponatremia in male rats. Am J Physiol Regul Integr Comp Physiol 323(5):R797-R809. doi: 10.1152/ajpregu.00086.2022 PMID: 36189988
Objective: Authors hypothesized that the A1/A2 noradrenergic neurons support chronic release of arginine vasopressin in cirrhosis leading to dilutional hyponatremia.
Summary: Dilutional hyponatremia associated with liver cirrhosis is due to inappropriate release of arginine vasopressin (AVP). The A1/A2 neurons stimulate the release of AVP from the supraoptic nucleus (SON) in response to nonosmotic stimuli. Injection of Anti-DBH-SAP (Cat. # IT-03) resulted in: 1) significantly reduced number of DBH immunoreactive A1/A2 neurons, 2) significantly reduced number of A1/A2 neurons immunoreactive to both DBH and Delta FosB positive neurons, 3) reduced number of SON neurons immunoreactive to both AVP and Delta FosB, 4) preventing the increase in plasma copeptin observed in vehicle-injected common bileduct (BDL) rats, and 5) normalizing plasma osmolality and hematocrit as compared with vehicle injection. The data suggest that A1/A2 neurons contribute to increased plasma copeptin and hypoosmolality in male BDL rats.
Usage: Bilateral injection of Anti-DBH-SAP into the supraoptic nucleus at (50 ng/500 nL)
Related Products: Anti-DBH-SAP (Cat. #IT-03)
CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells
Kim S, Shukla RK, Yu H, Baek A, Cressman SG, Golconda S, Lee GE, Choi H, Reneau JC, Wang Z, Huang CA, Liyanage NPM, Kim S (2022) CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells. Front Immunol 13:1011190. doi: 10.3389/fimmu.2022.1011190
Objective: To use a new murine testing model to demonstrate a substantial enrichment of tissue-resident Foxp3+ Tregs following CD3e-IT treatment.
Summary: The multi-organ pharmacodynamics of CD3e-IT and potential treatment resistance mechanisms identified in this study may generate new opportunities to further improve this promising treatment.
Usage: Male C57BL/6J mice were injected into retro-orbital sinus with 15 μg S-CD3e-IT (Biotinylated Anti-CD3 mixed with Streptavidin-ZAP in sterile 200 μl PBS twice a day for four consecutive days.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
