Zhu M, Wu Y, Gao H, Qi F, Zhang X, Ran Y (2025) Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion. Commun Biol 8(1):911. doi: 10.1038/s42003-025-08314-2 PMID: 40500296
Objective: To explore why intrinsically photosensitive retinal ganglion cells (ipRGCs) are more resistant to ischemia/reperfusion (I/R) injury than other RGC subtypes and to examine the role of mTOR signaling in this differential vulnerability.
Summary: ipRGCs exhibited higher mTOR activity and greater resistance to I/R injury compared to other RGCs. Rapamycin had cell-type–specific effects: it protected non-ipRGCs by increasing mTOR activity but suppressed mTOR in ipRGCs unless light was removed, revealing that light conditions critically influence mTOR-mediated neuroprotection.
Usage: Melanopsin (OPN4) was detected using Anti-Melanopsin (AB-N39) at a 1:2000 dilution to identify and quantify ipRGCs in retinal whole-mounts following ischemic injury.
Ren X, Wang Y, Zhang Y (2025) Targeted depletion of dysfunctional hematopoietic stem cells mitigates myeloid-biased differentiation in aged mice. Cell Discov 11:56. doi: 10.1038/s41421-025-00810-3 PMID: 40490480
Objective: To develop and evaluate a targeted strategy for depleting dysfunctional, myeloid-biased CD150-high hematopoietic stem cells (HSCs) in aged mice to restore balanced hematopoiesis and mitigate aging-related blood disorders.
Summary: The study used an antibody-toxin conjugate to selectively eliminate CD150-high HSCs, improving lymphoid-to-myeloid ratios, reducing platelet hyperproduction, and restoring hematopoietic balance in aged mice. Treatment preserved functional CD150-low HSCs and showed minimal off-target or systemic toxicity.
Usage: Streptavidin-ZAP (IT-27) was combined with a biotinylated anti-CD150 antibody to generate Anti-CD150-SAP (IT-103). This conjugate was used at doses of 1–2 mg/kg in vivo and as low as 0.01 nM in vitro to specifically deplete CD150-high HSCs while sparing CD150-low populations.
Movahed AY, Bagheri R, Savatier P, Šarić T, Moradi S (2025) Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy. Stem Cell Reports 102543. doi: 10.1016/j.stemcr.2025.102543 PMID: 40541178
Objective: To review and evaluate current strategies for eliminating tumorigenic pluripotent stem cells (PSCs) from differentiated cell therapy products to improve the safety of PSC-based regenerative therapies.
Summary: Residual undifferentiated PSCs pose a tumorigenic risk in cell therapies. This review outlines genetic, antibody, toxin, and small molecule strategies for selectively removing PSCs, emphasizing the need for efficient, selective methods to ensure safety in regenerative medicine.
Usage: References a previous study that used Fab-ZAP to eliminate pluripotent stem cells by targeting specific surface markers, demonstrating its application as a targeted immunotoxin for PSC depletion.
Son S, Beaudoin DL, Hassan AR, Akpo MS, Ichinose T, Garrett AM (2025) A characterization of mouse retinal ganglion cell types labeled with AAV tools. bioRxiv 2025.06.02.657062. doi: 10.1101/2025.06.02.657062
Objective: To characterize the cell-type specificity and functional diversity of retinal ganglion cells (RGCs) labeled by AAV vectors carrying synthetic promoters ProA13 and ProA27 in the mouse retina.
Summary: ProA13 and ProA27 AAV vectors selectively labeled molecularly and morphologically distinct subsets of RGCs, including melanopsin-positive ipRGC subtypes. ProA27 labeled a broader diversity of ipRGCs (M1–M4), while ProA13 primarily labeled M1 cells, enabling analysis of their structural, functional, and projection differences.
Usage: Melanopsin (OPN4) was detected using Anti-Melanopsin (AB-N38) at a 1:5000 dilution to identify and classify ipRGCs in AAV-labeled retinas.
Anderson KL (2025) Neural mechanisms of context-sensitive behavior in the adult male zebra finch. City Univ NY Thesis.
Objective: To test whether oxytocin and dopamine mediate the influence of the social behavior network on the vocal control network in songbirds, enabling context-dependent changes to song.
Summary: The study reveals direct anatomical links between hypothalamic nodes of the social behavior network and the vocal control network. Blocking oxytocin receptors disrupts appropriate female-directed song and correlated network activity.
Usage: To assess brain access and persistence of intranasal compounds, Oxytocin-SAP (IT-46) was delivered intranasally at 1 μg/ml (12 μL total, 0.0012 mg per bird).
McLeod CM, Son S, Haque MN, Garrett AM (2025) Reduced neuronal self-avoidance in mouse starburst amacrine cells with only one Pcdhg isoform. bioRxiv 2025.05.29.656828. doi: 10.1101/2025.05.29.656828
Objective: To determine whether the γC4 isoform of the protocadherin-γ (Pcdhg) gene cluster is sufficient to mediate neuronal self-avoidance in starburst amacrine cells (SACs) in the mouse retina.
Summary: While deletion of γC4 or γC5 alone did not impair SAC self-avoidance, mice expressing only γC4 exhibited significant failures in dendritic self-avoidance that were not fully rescued by transgenic overexpression. These findings suggest γC4 is specialized for neuronal survival but insufficient to support self-avoidance on its own.
Usage: Melanopsin (OPN4) was detected using Anti-Melanopsin (AB-N38) at a 1:2000 dilution to label intrinsically photosensitive retinal ganglion cells (ipRGCs) for analysis of retinal cell spacing and mosaic organization.
Chauhan P, Hu S, Sheng WS, Prasad S, Lokensgard JR (2025) bTRM control of murine cytomegalovirus cns reactivation. 26(11):5275. doi: 10.3390/ijms26115275 PMID: 40508083
Objective: To determine the role of CD8+ and CD103+ brain-resident memory T cells (bTRMs) in controlling murine cytomegalovirus (MCMV) reactivation in the central nervous system.
Summary: Depleting CD103+ bTRMs led to transient viral gene expression and delayed recovery of infectious virus from explants, implicating these cells in maintaining latency. bTRM depletion also triggered expression of disease-associated microglial genes, suggesting a role in modulating neuroimmune responses.
Usage: Anti-CD103-SAP (IT-50) was injected intracerebroventricularly (2 µg) to selectively deplete CD103+ bTRMs in latently infected mice. This targeted depletion achieved ~90% T-cell reduction and was critical for assessing viral reactivation and microglial activation phenotypes.
Roberts AG, Meyer L, Norton M, Phuah P, Alonso AM, Dowsett GKC, Cheng S, Dunsterville C, Liu J, Chung PE, Tao Y, Smitherman-Cairns T, Deutsch AB, Chatterjee A, Lam BYH, Hanyaloglu AC, JOnes B, Yeo GSH, Salem V, Murphy KG (2025) Enteropancreatic neurons drive the glucoregulatory response to ingested lipid. bioRxiv 2025.05.09.652620. doi: 10.1101/2025.05.09.652620
Objective: To determine whether NTSR1-expressing enteropancreatic neurons mediate the glucose-lowering effects of dietary olive oil and neurotensin, and to characterize their physiological role in glucose homeostasis.
Summary: The study demonstrates that neurotensin improves glucose tolerance by activating NTSR1-expressing enteropancreatic neurons, which connect the gut and pancreas. Ablation or disruption of these neurons abolished the glucoregulatory effects of both neurotensin and olive oil, establishing their necessity and sufficiency in this pathway.
Usage: Neurotensin-SAP (IT-56) or Blank-SAP (IT-21) was unilaterally injected into the nodose ganglia (0.5 μL at 1.5 μg/μL) to ablate NTSR1-expressing vagal neurons. This targeted lesioning helped confirm that peripheral vagal neurons were not responsible for mediating the glucose-lowering effects of neurotensin.
Semo M, Hughes S, Smyllie NJ, Patton AP, Pothecary CA, Tam SKE, Buckland J, Brown LA (2025) Magnetic fields influence visual responses in mice. bioRxiv 2025.05.12.653455. doi: 10.1101/2025.05.12.653455
Objective: To investigate whether magnetic fields influence mammalian retinal function and to determine the role of cryptochromes in mediating this effect.
Summary: This study demonstrates that magnetic fields modulate neuronal activity in the mouse retina in a light-dependent and cryptochrome-dependent manner. Magnetic fields altered c-Fos expression in melanopsin-positive retinal ganglion cells and influenced retinal circadian rhythms and behavior.
Usage: Melanopsin (OPN4) expression was assessed using Anti-Melanopsin (AB-N38) at a 1:2500 dilution to label ipRGCs during immunohistochemical analysis of retinal responses to light and magnetic fields.
Kozlova E, Lam A, Alam S, Shum J, Denys M, Berdasco C, de-Lartigue G, Curras-Collazo M (2025) Do CCKA receptor containing vagal afferent neurons mediate gut-brain inflammatory signals?. Am Physiol Soc 40(S1) doi: 10.1152/physiol.2025.40.S1.2035
Objective: To investigate whether CCKA receptor, containing vagal afferent neurons (VANs), mediate gut-brain inflammatory signaling and contribute to the systemic immune response following an LPS challenge.
Summary: This abstract reports that ablation of CCKAR+ VANs via CCK-SAP reduced LPS-induced IL-6 levels and brain c-Fos expression, indicating a blunted inflammatory response. These findings support the role of CCKAR+ VANs in gut-brain immune signaling and their potential as therapeutic targets.
Usage: CCK-SAP (IT-31) was bilaterally injected into the nodose ganglia (250 nL, 250 ng/μL) to ablate CCKA receptor–expressing vagal afferents.
