Biology subjects

Alamalhoda, M.

Publications and source records attributed to Alamalhoda, M..

3 recordsLinked to original sources

bioRxiv2025

Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia.

Anesthesia recovery is critical for resuming normal physiological and neuronal functions; however, the mechanisms involved remain elusive. Here, we identify a female-selective corticosterone-mediated microglia-neuron interaction in vivo during ketamine anesthesia recovery, absent in males. This microglia-neuron interaction induces plastic and functional neuronal changes, as evidenced by increased spine density and mEPSC frequency, which is occluded upon microglia depletion. We show that this process is driven through upregulation of the stress-responsive co-chaperone Fkbp5 mRNA and its protein, FKBP51, in female microglia. Fkbp5/FKBP51 is a key intermediary in a corticosteroid-induced stress response, and its involvement points towards a critical interface between endocrine signaling and microglia. Thus, to counteract the observed KXA-mediated corticosterone increase in the blood, we remove the primary source of corticosterone through adrenalectomy. Close microglia-neuron interaction was absent, but was reinstated after corticosterone injection. Our findings offer a new mechanism of microglia-mediated neuronal plasticity during anesthesia recovery, which is mediated through corticosterone, enhancing our understanding of sex differences in brain function.

neuroscience↗

bioRxiv2025

Flickering white light stimulation at 60 Hz induces strong, widespread neural entrainment and synchrony in healthy subjects

BackgroundWhile the effects of 40 Hz externally-induced neural entrainment have been extensively described, little is known about 60 Hz entrainment in humans. Given the role of 60 Hz in cognition, neuroplasticity and neuropsychiatric disorders, this warrants further investigation. ObjectivesThis pilot study characterizes, for the first time, the neural and somatic response to 60 Hz light entrainment in healthy volunteers, over a 3 week-period. MethodsFourteen volunteers were randomized to receive either 60 Hz flickering white light or constant light as sham (30-min sessions, for 3 weeks, 5 days a week). Neural entrainment was assessed with EEG on days 1, 5 and 19. Salivary cortisol and C-reactive protein (CRP) levels, measured with ELISA, assessed the somatic response to stimulation. Side effects and well-being were monitored via questionnaires. Results60 Hz flickering light induced a strong neural entrainment across visual, parietal, temporal and frontal cortex. The signal was highly synchronous but declined significantly by day 19 compared to day 1, indicating neural habituation. Cortisol and CRP salivary levels were unchanged and the stimulation was well tolerated. ConclusionsTo the best of our knowledge this is the first study to characterize both the neural and the somatic response to flickering light over 3 weeks. The observed neural habituation suggests that neuroplasticity could be induced with repeated stimulations over 3 weeks. 60 Hz stimulation for modulating brain activity and induce neuroplasticity has implications for our basic understanding of brain physiology as well as treatment of psychiatric disorders.

neuroscience↗

bioRxiv2024

Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye.

PurposeOptic nerve crush (ONC) is a model for studying optic nerve trauma. Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the affected eye, leading to vision loss within a month. A common assumption has been that the non-injured contralateral eye is unaffected due to the minimal anatomical decussation of the RGC projections at the chiasm. Yet, recently, microglia, the brain-resident macrophages, have shown a responsive phenotype in the contralateral eye after ONC. Whether RGC loss accompanies this phenotype is still controversial. MethodsUsing the available RGCode algorithm and developing our own RGC-Quant deep-learning-based tool, we quantify RGCs total number and density across the entire retina after ONC. ResultsWe confirm a short-term microglia response in the contralateral eye after ONC, but this did not affect microglia number. Furthermore, we cannot confirm the previously reported RGC loss between naive and contralateral retinas five weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained this discrepancy, suggesting that the early microglia-responsive phenotype does not have immediate consequences on the RGC number. ConclusionsOur results corroborate that unilateral optic nerve injury elicits a microglial response in the uninjured contralateral eye but without RGC loss. Therefore, the contralateral eye should be treated separately and not as an ONC control.

neuroscience↗