STEM with Science and Technical writing allows students to research a topic of their interest. We present our research in multiple ways: elevator pitches, poster presentations, grant prposal, and STEM thesis. This develops presentation skills, clarity, communication and more.
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This study investigates whether epilepsy can cause transgenerational cognitive impairments in Caenorhabditis elegans. Seizures were induced using PTZ, and spatial learning was assessed across three generations. Results show that even a single seizure exposure can impair learning in descendants, and repeated or ancestral exposures further exacerbate deficits. These findings suggest that seizure-induced epigenetic changes may be inherited, highlighting a potential link between epilepsy and increased dementia risk across generations.
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Epilepsy and Alzheimer’s disease are increasingly recognized as
comorbid neurological disorders, yet the mechanisms linking them remain
unclear. Seizure-induced neuroinflammation may drive epigenetic changes
that alter gene expression and can be inherited across generations,
potentially increasing dementia risk. This study investigates whether
epilepsy produces transgenerational cognitive impairments using
Caenorhabditis elegans as a model organism.
Seizures were chemically induced in C. elegans using pentylenetetrazole
(PTZ). Spatial learning and memory were assessed across three
generations using a T-maze chemotaxis assay. Worms were exposed to PTZ
either once or repeatedly across generations. Learning performance
during training and testing phases was compared to that of unexposed
controls.
Control worms consistently exhibited
robust spatial learning, with significant improvement during training
and testing (p < 0.0001). PTZ exposure impaired learning in both a
dose- and generation-dependent manner. In Generation 2, once-exposed
worms showed significantly reduced learning during training (p =
0.0003) and testing (p = 0.0018), while repeatedly exposed worms
displayed stronger deficits. In Generation 3, cumulative exposure
further exacerbated learning impairments, with repeatedly exposed worms
failing to show significant improvement during testing (p > 0.05).
Importantly, learning deficits persisted even after PTZ exposure was
discontinued, indicating lasting inherited effects.
These findings demonstrate that seizure exposure can induce durable,
transgenerational impairments in cognitive function. Together, the
results suggest that epilepsy may act as a transgenerational risk
factor for dementia, potentially mediated by heritable epigenetic
mechanisms. Future studies will examine DNA methylation and
amyloid-beta accumulation to identify targets for preventative
interventions.
Keywords: Epilepsy, Alzheimer’s,
dementia, epigenetics, transgenerational inheritance, C. elegans
How does dementia pathology in C. elegans change due to epilepsy over many generations?
If more generations of C. elegans are given seizures, then the future generations will have more dementia pathology because of inherited epigenetic modifications.
Epilepsy and Alzheimer’s disease (AD) are highly prevalent
neurological disorders affecting over 50 million people annually (Yang
et al., 2022). Research increasingly supports a bidirectional
relationship between them, driven by shared neuroimmune and
neuroinflammatory pathways (Stewart & Johnson, 2025). Epilepsy involves
recurrent seizures caused by genetic and environmental factors, with
many cases linked to structural or unknown etiologies (Zhang et al.,
2024). Chronic neuroinflammation in epilepsy can trigger epigenetic
modifications, including altered gene expression and DNA methylation
(Komada & Nishimura, 2022), which are implicated in AD pathogenesis
(Sharma et al., 2020). Because epigenetic changes can be
transgenerational (Fitz-James & Cavalli, 2022), epilepsy-related
molecular alterations may increase AD risk across generations.
C.
elegans serves as an effective model organism for studying these
mechanisms due to its mapped connectome, genetic simplicity, and
established use in epilepsy and AD research (Emmons et al., 2021;
Gourgou et al., 2021). Understanding these shared pathways can support
improved screening, prevention strategies, and the development of
future therapeutic targets.
This study utilized Caenorhabditis elegans unc-49 worms maintained on Nematode Growth Media (NGM) agar plates seeded with Escherichia coli OP50 (Brenner, 1974). Age-synchronized populations were obtained using a standard bleach protocol (Brenner, 1974). PTZ (pentylenetetrazole) exposure plates were prepared using a 0.5 g/mL stock solution applied to 100 mm NGM plates (Wong et al., 2018).
Worms were synchronized using bleach treatment and divided into four experimental groups: Control, 1-generation PTZ, 2-generation PTZ, and 3-generation PTZ. Worms were allowed to develop for two days prior to exposure to ensure consistent larval stage across groups. This technique was essential for controlling developmental variation, which could affect behavioral outcomes (Brenner, 1974).
PTZ exposure was performed to induce seizure-like neural activity and evaluate its effect on spatial learning across generations (Wong et al., 2018). Thirty synchronized worms were transferred to PTZ-treated plates for 10–15 minutes, then allowed to recover on standard NGM plates seeded with OP50 for at least one hour before behavioral testing. This approach enabled the assessment of neural excitability and cumulative effects across multiple generations.
The T-maze assay was employed to evaluate associative learning in C. elegans (Gourgou et al., 2021). Individual worms were placed at the starting point of the maze, with one arm containing OP50 as a food reward during training. Worm distribution was recorded after a 5-minute training phase, followed by a second trial 5 minutes later on a new maze, and finally on an empty maze to assess memory and navigation in the absence of food cues. This assay justified evaluating PTZ’s impact on learning and memory in a multisensory context.
Z-proportion tests were used to determine the significance of differences in worm choice behavior between control and PTZ-treated groups. This test was appropriate because the outcome of the spatial learning assay is categorical (selection of conditioned vs. unconditioned maze arms) and allows comparison of proportions between independent groups.
The Z-proportion test compared the observed proportion of worms selecting the conditioned arm to the expected probability by chance (0.5). This approach was suitable for categorical data with sufficient sample sizes and provided a statistical framework for evaluating whether the choices of worms were non-random and significantly influenced by treatment.
