Biology subjects

Do, A. D.

Publications and source records attributed to Do, A. D..

3 recordsLinked to original sources

bioRxiv2025

Protective ApoE variants support neuronal function by extracting peroxidated lipids

ApoE mediates the transport of lipids from neurons to glial lipid droplets. ApoE4, a major risk factor for Alzheimer's disease, impairs this transport pathway, increasing risk for neurodegeneration. ApoE2 and ApoE3 Christchurch (ApoE3Ch) variants confer resistance to developing the disease, yet little is known regarding how these protective variants affect lipid transport. Here, we explored how lipoprotein particles containing different ApoE isoforms affect neuronal health in vitro and in intact rodent hippocampi. We demonstrate that ApoE2 and ApoE3Ch particles protect neurons from ferroptosis by preferentially extracting peroxidated unsaturated lipids through the neuronal ABCA7 transporter. ApoE4 particles, on the other hand, exacerbate the effects of these toxic lipids leading to endolysosomal dysfunction. By reducing the peroxidated lipid burden in ApoE4 neurons, ApoE2 and ApoE3Ch particles rescue endolysosomal function and restore defects in neuronal activity. Our findings reveal a new mechanism by which ApoE2 and ApoE3Ch isoforms protect neurons from neurodegenerative disease.

neuroscience↗

bioRxiv2023

State dependent constraints on claustrocortical communication and function

Neural activity in the claustrum has been associated with a range of vigilance states, yet the activity patterns and efficacy of synaptic communication of identified claustrum neurons have not been thoroughly determined. Here we show that claustrum neurons projecting to the retrosplenial cortex were most active during synchronized cortical states such as non-rapid-eye-movement (NREM) sleep and were suppressed during increased cortical desynchronization in arousal, movement, and REM sleep. The efficacy of claustrocortical signaling was also increased during NREM and diminished during movement due in part to increased cholinergic tone. Finally, claustrum activation during NREM sleep enhanced memory consolidation through the phase-resetting of cortical delta waves. Therefore, claustrocortical communication is constrained to function most effectively during cognitive processes associated with synchronized cortical states, such as memory consolidation. Key PointsO_LIClaustrum neurons are suppressed/activated during desynchronized/synchronized cortical states C_LIO_LIClaustrocortical connectivity is increased in non-REM and suppressed during movement C_LIO_LIClaustrocortical communication is heightened during low cholinergic tone C_LIO_LIClaustrum - modulated cortical delta waves enhance the consolidation of a labile memory C_LI

neuroscience↗

bioRxiv2020

Topographic gradients define the projection patterns of the claustrum core and shell in mice

The claustrum is densely connected to the cortex and participates in brain functions such as attention and sleep. Although some studies have reported the widely divergent organization of claustrum projections, others describe parallel claustrocortical connections to different cortical regions. Therefore, the details underlying how claustrum neurons broadcast information to cortical networks remain incompletely understood. Using multicolor retrograde tracing we determined the density, topography, and co-projection pattern of fourteen claustrocortical pathways, in mice. We spatially registered these pathways to a common coordinate space and found that the claustrocortical system is topographically organized as a series of overlapping spatial modules, continuously distributed across the dorsoventral claustrum axis. The claustrum core projects predominantly to frontal-midline cortical regions, whereas the dorsal and ventral shell project to the cortical motor system and temporal lobe, respectively. Anatomically connected cortical regions receive common input from a subset of claustrum neurons shared by neighboring modules, whereas spatially separated regions of cortex are innervated by different claustrum modules. Therefore, each output module exhibits a unique position within the claustrum and overlaps substantially with other modules projecting to functionally related cortical regions. Claustrum inhibitory cells containing parvalbumin, somatostatin, and neuropeptide Y also show unique topographical distributions, suggesting different output modules are controlled by distinct inhibitory circuit motifs. The topographic organization of excitatory and inhibitory cell types may enable parallel claustrum outputs to independently coordinate distinct cortical networks.

neuroscience↗