Biology subjects

Carrion, A. M.

Publications and source records attributed to Carrion, A. M..

3 recordsLinked to original sources

bioRxiv2026

HERC1 Loss of Function Causes a Developmental Disorder with Impaired Hippocampal Function

Pathogenic variants in HERC1 are associated with a syndromic neurodevelopmental disorder characterized by macrocephaly, developmental delay, intellectual disability, and psychomotor dysfunction. Although genetic and molecular studies suggest a loss-of-function mechanism, definitive in vivo evidence that HERC1 deficiency is sufficient to cause neurodevelopmental abnormalities is lacking. Using a HERC1 knockout mouse model, we investigated the behavioural, neuronal, and synaptic consequences of complete HERC1 loss. HERC1 deficiency caused motor coordination and cognitive deficits in both sexes, while male mutants additionally displayed hyperactivity and increased anxiety-like behaviour. Histological analyses revealed selective hippocampal abnormalities, including disruption of dentate gyrus organization, whereas Purkinje cells survival and cerebellar compartmentalization remained preserved. HERC1-deficient mice exhibited a marked increase in hippocampal GABAergic interneurons, impaired maturation of dendritic spines in CA1 pyramidal neurons, and altered adult neurogenesis, indicating widespread defects in hippocampal circuit organization. Consistent with these structural abnormalities, glutamatergic synaptic components were significantly altered throughout the hippocampus. These molecular changes showed a sex-dependent pattern, with predominantly presynaptic defects in males and postsynaptic alterations in females. Despite these differences, whole-cell recordings revealed a common functional phenotype in both sexes. At both mossy fibre-CA3 and Schaffer collateral-CA1 synapses, HERC1-deficient neurons exhibited a progressive inability to sustain excitatory neurotransmission during repetitive stimulation, resulting in impaired steady-state glutamatergic transmission. Together, these findings demonstrate that loss of HERC1 function is sufficient to produce a neurodevelopmental phenotype and identify HERC1 as a critical regulator of hippocampal circuit assembly and function. Our results provide mechanistic insight into the pathogenesis of HERC1-associated disorders and establish the Herc1 knockout mouse as a preclinically relevant model for investigating disease mechanisms and therapeutic approaches.

neuroscience↗

bioRxiv2019

WHO child growth standards for Pygmies: one size fits all?

BackgroundAfrican Pygmies exhibit a unique, genetically determined child growth dynamics and adult stature but the impact on assessing undernutrition remains unknown. Baka Pygmy health is highly compromised compared to sympatric populations. Evaluating child undernutrition is an important step to address this health quandry. We estimate stunting and wasting in Cameroons Baka children and investigate the applicability of the standards for Pygmy people.\n\nMethodsAnthropometric and health data from 685 2-to12 year old children were collected at 25 health centres in southern Cameroon. Growth was analysed using both, WHO Child Growth Standards and the population itself as reference to define frequencies of stunting, wasting and obesity.\n\nFindingsBaka children revealed with 68.4% the highest recorded level globally of stunting relative to the WHO child growth standard in 2-to-4 year olds. Wasting was at 8.2% in the upper third range in Sub-Saharan Africa. Obesity was with 6.5% similar to wasting, but no comparable data have been published for Sub-Saharan Africa. When referenced to the Baka population itself, values for stunting were dramatically lower at 1.0% and 2.9% for 2-to-4 and 5-to-12 year olds, respectively. Wasting was also lower at 2.8% and 1.8% and was exceeded by obesity at 3.4% and 3.5%, respectively. Brachial perimeters and oedemas indicated rare severe malnutrition (< 2%) whilst moderate and severe anaemia were frequent (26.6% and 3.3%, respectively).\n\nInterpretationWHO child growth standards for stunting are clearly not applicable to Pygmies thus contradicting the widespread emphasis of their ethnicity-independent applicability. The inferred values for wasting and obesity are also difficult to interpret and are likely overestimated by the WHO criteria. To achieve UN Sustainable Development Goals and to fulfil our humanitarian responsibility for fellow man, we recommend that Pygmy specific growth standards are developed for the genetically differing Pygmy tribes.

scientific communication and education↗

bioRxiv2019

Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

Aging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity by a still not fully understood mechanism. We find that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones and increases longevity. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) and is not additive to the longevity of germline-less mutants. Noteworthy, sul-2 mutations do not affect fertility. Thus, STS inactivation affects the germline signalling process regulating longevity. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of germline longevity by environmental cues. We also demonstrate that treatment with the specific STS inhibitor STX64, reproduces the longevity phenotype of sul-2 mutants. Remarkably, STS inhibition by either mutation or drug treatment ameliorates protein aggregation diseases in C. elegans models of Parkinson, Huntington and Alzheimer, as well as Alzheimer disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors for the treatment of aging and aging related diseases.

developmental biology↗