bioRxiv Science⌕ Search

Biology subjects

Wijethunga, S.

Publications and source records attributed to Wijethunga, S..

2 recordsLinked to original sources

Early life adversity enhances prosocial helping towards a cagemate and reshapes brain-wide neural activity and network organization

Early life adversity (ELA) is linked to changes in social behavior and emotional regulation and to increased risk for developing mood and conduct disorders. However, the effects of ELA on empathy and its associated behaviors, including prosocial helping, remain poorly understood. Animal models of ELA provide a tractable way to study how early rearing conditions impact prosocial behavior and underlying neural circuitry. In the current study, adult male and female rats reared under maternal separation (MS) or control conditions were tested in a helping behavior task in which they could release a trapped cagemate. Behavior was assessed across repeated testing sessions and brain-wide neural activity was quantified using c-Fos on the final test day. Contrary to our hypothesis, we found that MS-reared rats showed more consistent helping behavior, with shorter latencies to help on average, compared to control-reared animals. In addition, MS-reared rats displayed increased social play following release. At the neural level, MS-reared rats displayed more c-Fos expression across multiple brain regions, including prefrontal, amygdala, sensory, and striatal regions involved in motivation and social decision making. Network analyses further revealed altered functional connectivity in ELA-reared animals, with heightened connectivity in stress-related regions such as the lateral habenula. Together, these findings demonstrate that ELA impacts prosocial helping behavior and is associated with widespread changes in neural activity and network organization. This work provides insight into how early adversity shapes social motivation and the neural systems supporting prosocial behaviors.

neuroscience↗

CNS-Tau Specific Antibodies Illuminate Disease Signatures Across Tauopathies

BackgroundAlternative splicing of the MAPT gene produces distinct tau isoforms in the central and peripheral nervous systems (CNS and PNS), yet their respective biological and pathological roles remain poorly understood. Recent studies suggest that CNS-tau may play a key role in amyloid-{beta} associated neurodegeneration in Alzheimers disease (AD), but the absence of isoform-specific tools has limited both mechanistic insight and biomarker development. We aimed to develop and validate CNS-tau-specific monoclonal antibodies and assess their utility in neuropathology and fluid-based biomarker assays across AD and primary tauopathies. MethodsWe generated six recombinant rabbit monoclonal antibodies targeting a CNS-tau-specific sequence encoded by exons 4 and 5. Specificity and affinity were evaluated via biolayer interferometry, immunoblotting, and tau-expressing HEK293 models. The lead clone, LL-T-1-1, was tested in postmortem brain sections from AD (n = 23), progressive supranuclear palsy (PSP, n = 3), and corticobasal degeneration (CBD, n = 3). A second clone, LL-T-1-5, was optimized for use in plasma assays via an ultrasensitive nanoneedle platform, LoD < 1 pg/ml. ResultsLL-T-1-1 showed nanomolar affinity for CNS-tau and no cross-reactivity with PNS-tau. It selectively labeled dystrophic neurites in AD and all hallmark tau lesions in PSP and CBD without antigen retrieval. LL-T-1-5-based plasma assays revealed CNS-tau levels significantly correlated with cognitive scores (MMSE and QDRS) and differentiated impaired from unimpaired individuals. ConclusionsCNS-tau-specific antibodies LL-T-1-1 and LL-T-1-5 provide new tools for neuropathology and fluid biomarker development across tauopathies.

neuroscience↗