Biology subjects

Lim, L. W.

Publications and source records attributed to Lim, L. W..

4 recordsLinked to original sources

bioRxiv2025

Impact of Choline intake during pregnancy on maternal cognition and hippocampal gene signature in old age

Women are twice as likely to have Alzheimers disease (AD) than men and multiparity has been suggested to be a risk factor for dementia. The present study evaluated whether the lack of certain nutrients during pregnancy influences cognition while pregnant and in old age in mouse model. Non-targeted NMR analysis revealed significantly lower levels of numerous plasma nutrients and metabolites including choline and its derivatives on gestation day 7 compared to day 1. Novel object recognition and Morris Water Maze tests revealed impaired cognition in pregnant mice compared to nonpregnant controls. Choline deprivation worsened the cognitive impairment during pregnancy and choline supplementation alleviated it. Furthermore, choline availability during pregnancy affected cognition and general health in old age, with mice given a choline-deficient diet during pregnancy performed more poorly. RNA-Seq analysis indicates lasting effect of choline intake during pregnancy on hippocampal gene signatures in old age. Choline deprivation was associated with more upregulation of proinflammatory genes, whereas choline supplementation showed upregulation of neuroprotective genes such as Prl, Gh, and hemoglobin (Hba and Hbb subunits). Together, the study shows that choline supplementation benefits cognitive health in women during pregnancy and in old age.

animal behavior and cognition↗

bioRxiv2020

Dropout in Neural Networks Simulates theParadoxical Effects of Deep Brain Stimulation onMemory

Neuromodulation techniques such as Deep Brain Stimulation (DBS) are a promising treatment for memory-related disorders including anxiety, addiction, and dementia. However, the outcome of these treatments appears to be paradoxical, as the use of these techniques can both disrupt and enhance memory even when applied to the same brain target. In this paper, we hypothesize that disruption and enhancement of memory through neuromodulation can be explained by the dropout of engram nodes. We used a convolutional neural network to classify handwritten digits and letters, applying dropout at different stages to simulate DBS effects on engrams. We showed that dropout applied during training improves the accuracy of prediction, whereas dropout applied during testing dramatically decreases accuracy of prediction, which mimics enhancement and disruption of memory, respectively. We further showed that transfer learning of neural networks with dropout had increased accuracy and rate of learning. Dropout during training provided a more robust "skeleton" network where transfer learning can be applied, mimicking the effects of chronic DBS on memory. Overall, we show that dropout of nodes can be a potential mechanism by which neuromodulation techniques such as DBS can both disrupt and enhance memory and provides a unique perspective on this paradox.

neuroscience↗

bioRxiv2019

Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation-induced anticipatory fear in a rat model

BackgroundElectrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful tool for modelling anticipatory fear and agoraphobia.\n\nMethodsIn this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then used tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons.\n\nResultsAlthough acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, chronic administrations of both drugs were comparably effective. We found that the number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups. We showed a strong correlation between the number of dopaminergic neurons and freezing in the VTA. We further showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.\n\nLimitationsAlthough our data strongly hint to a role of dopaminergic mechanisms in the dlPAG induced fear response, more in-depth studies with larger sample sizes are needed to understand the neuronal mechanisms underlying the interactions between serotonergic drugs and dopaminergic cell number and fear behavior.\n\nConclusionChronic treatment with an SSRI and a 5-HT1A agonist decrease the number of dopaminergic neurons in the VTA. These effects seem to be associated with reduced dlPAG-induced anticipatory freezing behaviour.\n\nKey PointsO_LIChronic treatment of escitalopram and buspirone was effective in reducing dlPAG induced anticipatory freezing behaviour.\nC_LIO_LIThe number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups and was correlated to freezing.\nC_LIO_LIWe found positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.\nC_LI

neuroscience↗

bioRxiv2019

Deep Brain Stimulation of the Ventromedial Prefrontal Cortex Disrupts Consolidation of Fear Memories

Anxiety disorders pose one of the biggest threats to mental health worldwide, yet current therapeutics have been mostly ineffective due to issues with relapse, efficacy, and toxicit. Deep brain stimulation (DBS) is a promising therapy for treatment-resistant psychiatric disorders including anxiety, but very little is known about the effects of DBS on fear memories. In this study, we used a modified plus-maze discriminative and showed that DBS of the ventromedial prefrontal cortex (vmPFC) was able to disrupt consolidation, but not acquisition or retrieval of fear memories. We validated these results using a standard tone-footshock fear conditioning paradigm. We further demonstrated short-term changes in dopaminergic receptor and c-Fos expression in the ventral hippocampus (vHPC) and established a partial casual role of dopamine 2 receptors in this effect. Lastly, we showed changes in neurotransmitter levels in the vHPC. This study highlights the potential therapeutic effect of vmPFC DBS to treat anxiety disorders.

neuroscience↗