Biology subjects

Bourojeni, F. B.

Publications and source records attributed to Bourojeni, F. B..

3 recordsLinked to original sources

bioRxiv2026

SorCS1 promotes synaptic and cognitive resilience despite amyloid pathology in Alzheimer's disease model mice

Alzheimer's disease (AD) lacks effective therapies despite extensive efforts targeting amyloid {beta} (A{beta}) and its precursor processing. Synapse loss is the strongest correlate of cognitive decline, driven partly by A{beta} oligomers (A{beta}Os), which bind multiple synaptic membrane proteins including the synaptic organizer neurexin and disrupt synaptic integrity and function. The protein sorting receptor SorCS1 blocks interactions between A{beta}Os and {beta}-isoforms of neurexins ({beta}-Nrxns), but its therapeutic relevance in vivo remains unclear. Using 5xFAD mice, which overproduce A{beta}Os, combined with forebrain specific neuronal SorCS1 overexpression, we show that SorCS1 preserves working memory, synaptic integrity, and basal excitatory transmission without altering amyloid deposition, in part by restoring synaptic {beta}-Nrxn expression. SorCS1 also reduces tau hyperphosphorylation in 5xFAD synaptosomes and binds the tau kinase GSK3{beta}. These results identify SorCS1 as an AD resilience promoting factor that maintains synaptic connectivity and attenuates tau pathology, revealing a therapeutic strategy that operates independently of amyloid reduction.

neuroscience↗

bioRxiv2026

A neuronal pathway for the supraspinal relay of warm and cool sensation

Cutaneous thermosensation is a fundamental sense allowing discrimination of external temperature changes and driving adaptive responses essential for survival and well-being. This sensory process begins with the activation of peripheral thermoreceptors, which encode the quality and intensity of thermal stimuli into neuronal activity that is further integrated by spinal cord circuits and relayed to supraspinal centres through the anterolateral tract (ALT). While classical experiments identified thermal responsive ALT neurons in the superficial spinal dorsal horn, the functional logic of innocuous temperature relay remains poorly understood. We show that, in mice, the majority of Phox2a-lineage lamina I ALT are selectively tuned to innocuous warming or cooling, and receive direct inputs from peripheral thermoreceptors. Their genetic ablation, chemogenetic or optogenetic manipulation impaired temperature discrimination. Our findings contrast with the previous finding that the majority of ALT neurons being mechano- and thermo-nociceptive and provide novel evidence for the existence of a large ensemble of genetically defined warming- and cooling- responsive ALT neurons. The large representation of innocuous temperature in supraspinal-relaying ALT neurons indicates substantial spinal amplification of thermal information and underscores the importance of innocuous thermosensation in the ascending sensory pathway.

neuroscience↗

bioRxiv2020

Phox2a defines a developmental origin of the anterolateral system in mice and humans

Anterolateral system neurons relay pain, itch and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that virtually all mouse spinal neurons that embryonically express the autonomic system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define Phox2a anterolateral system neuron birth order, migration and differentiation, and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human foetal spinal cord. The developmental expression of Phox2a as a uniting feature of anterolateral system neurons suggests a link between nociception and autonomic nervous system function.

neuroscience↗