NEURO NUGGETS

BY DR MOHD WAEL

Dr Wael MY Mohamed is with the Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic University Malaysia( IIUM).

Investigators from KU Leuven and the VIB Institute have successfully identified key molecular mediators governing this process, demonstrating the power of collaborative research in advancing our understanding of neurodegenerative diseases.

The zebrafish( Danio rerio), a cyprinid teleost fish characterised by distinctive lateral striations and an adult size of 3-5 cm, presents a formidable model organism for biomedical research, piquing the interest of researchers and science enthusiasts alike.

Its salient features include external embryonic development with rapid organogenesis( core structures forming within 24 hours post-fertilisation and hatching occurring by 72 hours), optical translucency facilitating in vivo microscopic observation, high fecundity with sexual maturity reached by three m o nt h s, a n d approximately 90 per cent genetic homology with humans.

Crucially, the tractability of its genome for m a n i p u l at i o n permits robust m o d e l l i n g o f human disease

pathways.

By employing zebrafish for molecular neurobiological investigation, researchers discovered a novel regulatory axis that controls neurogenesis.

Neural stem cells( NSCs), undifferentiated progenitors with neurogenic potential, play a fundamental role in brain development and maintenance in both zebrafish and humans.

WELL-ESTABLISHED

While the Notch signalling pathway is a well-established regulator of NSC maturation during embryogenesis, its dysregulation in neurodegenerative contexts, such as Alzheimer ' s disease( AD), remains poorly characterised.

This study focused on microRNA-132( miR-132), a post-transcriptional regulator that modulates genes involved in the Notch signalling cascade.

Their investigation targeted miRNA-132 ' s role in modulating Notch signalling within NSCs. " miRNA-132 is implicated in maintaining plasticity in the mature mammalian brain, where residual NSCs persist.

Notably, its activity is markedly diminished in AD and other neurodegenerative conditions involving neuronal loss. Utilising zebrafish, where miRNA-132 levels can be efficiently knocked down, we modelled this deficiency.

These miRNA-132-deficient zebrafish exhibited impaired NSC maturation. Subsequent molecular profiling delineated the involved pathway components.

Notably, the observed reduction of miRNA-132 in the AD brain parallels the findings in the zebrafish model. They

demonstrated that attenuated miRNA- 132 activity in zebrafish obstructs NSC differentiation into mature neurons.

This work precisely delineates the molecular signalling cascade responsible, revealing the specific blockade mechanism. These findings in zebrafish provide a critical foundation for dissecting the analogous pathological sequence in the human AD brain.

Consequently, the research team has initiated complementary studies utilising murine models and post-mortem human AD brain tissue.

CLINICAL IMPLICATIONS

This research identifies miRNA-132 and its downstream Notch signalling effectors as potential therapeutic targets for Alzheimer ' s disease and related dementias.

Restoring miRNA-132 function or modulating its specific targets could rescue impaired neurogenesis and enhance neural plasticity, offering avenues for disease-modifying therapies.

Furthermore, miRNA-132 levels or associated pathway components may serve as novel diagnostic or prognostic biomarkers, enabling earlier detection and monitoring of neurodegenerative progression.

CONCLUSION

They might look like tiny zebras in swimsuits, but these little fish are secretly brainy superheroes.

No, they won ' t win Nobel Prizes or write lab diaries— but thanks to their see-through heads, they ' re helping scientists unlock the mysteries of our brains. Who knew brain research could be such a fishy business?- The HEALTH