Søren Grubb

Double PI act @sorengrubb.bsky.social @amreenmughal.bsky.social continuing in brains with #cilia & #centrosome diversity across microvascular system, with striking species differences on cilia metrics & directionality of spaces sampled. Deep read: www.biorxiv.org/content/10.1... #UKCilia 5/8

Want to know about our latest research on #primarycilia and #centrosomes in #brain #microvasculature? Join this e-symposium tomorrow! 🧪

Thanks for a great 2025!🎆🥳🎉

We’re proud to share highlights from this year at Neuroscience Academy Denmark (NAD) – showcasing the incredible work of our PhD students. 👩‍🎓👨‍🎓

A big thank you to @lundbeckfonden.bsky.social for supporting our mission. 🙏

#Neuroscience #PhD #Research #Collaboration 🧪

Also thanks to @helenelab.bsky.social for access to the CA1 dataset!

a man in a suit and tie is giving a thank you sign . ALT: a man in a suit and tie is giving a thank you sign .

We would like to acknowledge the amazing #OpenScience #ElectronMicroscopy datasets by @alleninstitute.org ‬, @hhmijanelia.bsky.social and other sources!
This work is a collaboration between me at @ucph.bsky.social, @amreenmughal.bsky.social and Vanshika at #NIH, and Carolyn and Jennifer at #Janelia

Graphical abstract showing gradient distribution of primary cilia in the mural cells. Primary cilium frequency and lengths are reversely proportional to smooth-muscle actin expression.

🧩 Summary:
✅ #Pericytes have #PrimaryCilia with an arterio-venular gradient🏳️‍🌈
✅ 🚶‍♀️🧠 ECs have primary #cilia, 🐁🧠 ECs don’t
✅ EC polarity aligns opposite to #BloodFlow 🧭
❔Lots of open questions about cilia’s role in #NeurovascularCoupling!
Read the full preprint: 🔗 www.biorxiv.org/content/10.1...
🧪🧵8/8

🧭 #EndothelialCells are polarized against #BloodFlow direction ⤴️. #Centrioles are consistently upstream of the #nucleus. This polarity persists even in fixed tissue and could serve as a structural marker for flow direction. 📌
🧪🧵7/8

A schematic illustration of the neurovascular unit highlighting primary cilia in ECs.

😮Surprise: 🚶‍♀️🧠 #EndothelialCells (EC) have #PrimaryCilia facing the vessel lumen, but 🐁🧠 ECs don’t. ~18% of 🚶‍♀️🧠 ECs are ciliated, mostly in arteriolar-end capillaries. What do these #cilia sense in the 🩸?
🧪🧵6/8

In 🐁, some #pericyte #PrimaryCilia penetrate #astrocytic #endfeet and reach the #neuropil - sometimes near #synapses! Could these #cilia act as sensory “antennae” 📡for #NeurovascularCoupling?
🧪🧵5/8

In 🐁🧠, #ultrastructure shows that #pericyte #cilia are often ensheathed by #astrocytic #endfeet. In 🚶‍♀️🧠, #astrocytes are swollen and cilia stay confined within the basal lamina. What are they sensing from the astrocytes?
🧪🧵4/8

🗺️We mapped #MuralCells — including #pericytes and #smoothmuscle — as vectors➡️ to visualize where #PrimaryCilia🌟 occur across the 🐁🧠 #microvasculature.
The result? A striking pattern: #cilia are abundant on #capillaries and #venules, but almost absent on #arterioles.
🧪🧵3/8

(d) Percent distribution of primary cilia in MCs after microvascular stratification into pial and parenchymal vessels, including 1-3rd order capillaries from the MICrONS (mouse visual cortex), CA1 (mouse hippocampus), and h01 (human cortex) datasets. Note that neither CA1 nor h01 contain any pial vessels. (e) Lengths of MC primary cilia in pial and parenchymal vessels, including 1-3rd order capillaries MCs from MICrONS.

📊 #Pericytes are frequently ciliated in both 🐁 and 🚶‍♀️🧠—but mostly near #venules and venous-end #capillaries.
Venular mural cells: up to 90% ciliated in 🐁 datasets!
Arteriolar mural cells: almost none.
Why this gradient? Flow, pressure, permeability?
🧪🧵2/8

New on bioRxiv! 🚨
“Pericyte and Endothelial Primary Cilia and Centrioles have Disparate Organization Across the Brain Microvasculature”
This project studying #microvascular cells took an unexpected turn when we discovered that #pericytes have primary #cilia!
🔗 www.biorxiv.org/content/10.1...
🧪 🧵1/8

@martienkas.bsky.social @brittae.bsky.social @dresler.bsky.social

🎥 NAD 2025 Annual Meeting Highlights
From Oct 3–5, Neuroscience Academy Denmark hosted:
✅ 400+ participants
✅ 100 posters
✅ Keynotes on precision psychiatry, brain barriers, ultrasound treatments, brain stimulation, sleep & circadian rhythms

We look forward to next year!
#Neuroscience #NAD2025 🧪

That reminds me of Thor fighting “midgårdsormen” the world serpent 🤣

“Well I don’t like that study because it doesn't give me the result I want’

We are excited to report:
Cerebral blood flow is modulated by astrocytic cAMP elevation independently of IP3R2-mediated Ca2+ signaling in mice
Vittani et al. PNAS (2025)
pnas.org/doi/10.1073/...

The first Master’s student with me as main supervisor graduated today! I’m proud 🥹

Thanks Amreen! ❤️

Brain precapillary sphincters modulate myogenic tone in adult and aged mice - GeroScience Brain precapillary sphincters, which are surrounded by contractile pericytes and are located at the junction of penetrating arterioles and first-order capillaries, can increase their diameter by ~ 30%...

🔗 Full Open Access manuscript: link.springer.com/article/10.1...
👇 Curious to hear more about #PrecapillarySphincters?
Check out these threads about the subject:
Characterization: x.com/SorenGrubb/s...
Ultrastructure: x.com/SorenGrubb/s...

In older mice, where #MyogenicTone is weaker, #PrecapillarySphincters become even more critical barriers against #BloodPressure surges—compensating for #VascularStiffening and remodeling.

These changes suggest that #PrecapillarySphincters protect the capillaries 🛡️ by acting as a dynamic #resistance that regulates #capillary #BloodFlow and #BloodPressure.

Using #InVivo #VolumeImaging, we found #age related #vascular changes:
• ↑ #Tortuosity of #PenetratingArterioles
• ↓ #Arteriolar-capillary density
• ↑ #Capillaries at the venous end + #aneurysm-like bulbs downstream of #PrecapillarySphincters.

By recording #cortical #angiograms during i.v. injection of FITC-dextran 🟢 in #adult and #old #NG2DsRed mice, we time-colored the #arterioles 🔴 and #venules 🔵. We found that #OldMice have less #collaterals and more #tortuous #PenetratingArterioles.

Figure showing how we used the two-photon laser to ablate the pericyte around the precapillary sphincter.

After #LaserAblating pericytes around #PrecapillarySphincters, we observed impaired #MyogenicResponse and #NeurovascularCoupling—demonstrating #PrecapillarySphincter pericyte contractility is essential.

Figure showing how we measured microvascular diameters by transverse line scanning to assess the diameter pulsatility and the pulsatility of the centers of the vessels.

#OldMice also showed decreased pulsations of microvessel diameters measured by transverse line scans, likely due to #VascularStiffening.

Figure showing blood pressure increase by the acute hypertensive challenge along with changed microvascular diameter in adult and old mice. CC= 0.13 for the adult mouse and 0.57 for the old mouse.

In aged mice, the #MyogenicResponse was significantly blunted. This was shown by an increased #CorrelationCoefficient (CC) between #VascularDiameter and #BloodPressure

We challenged mice with acute #BloodPressure spikes (~70% increase via angiotensin II). Result: both adult and #old mice got their #MyogenicResponse and #NeurovascularCoupling disrupted

To visualize this, we used #InVivo #TwoPhotonMicroscopy in anesthetized adult and aged mice. Watch this video showing PS dilation in response to “SensoryStimulation! 🔬👇