Biology subjects

Dura, I.

Publications and source records attributed to Dura, I..

3 recordsLinked to original sources

bioRxiv2024

Traumatic brain injury enhances the intrinsic excitation and excitatory transmission of granule cells

Traumatic brain injury (TBI) leads to a wide range of long-lasting physical and cognitive impairments. Changes in neuronal excitability and synaptic functions in the hippocampus have been proposed to underlie cognitive alterations. The dentate gyrus (DG) acts as a "gatekeeper" of hippocampal information processing and as a filter of excessive or aberrant input activity. In this study, we investigated the effects of controlled cortical impact, a model of TBI, on the excitability of granule cells (GCs) and excitatory postsynaptic transmission in the DG at three time points, 3 days, 15 days and 4 months after the injury. Our results indicate that changes in the short term are related to intrinsic properties, while changes in the long term are more related to input and synaptic activity, in agreement with the notion that TBI-related pathology courses with an acute phase and a later long-term secondary phase. A biphasic response, a reduction in the shorter term and an increase in the long term, was found in TBI neurons in the frequency of sEPSC. These changes correlated with a loss of complexity in the pattern of the synaptic input, an alteration that could therefore play a role in the chronic and recurrent TBI-asssociated hyperexcitation.

neuroscience↗

bioRxiv2023

Traumatic brain injury modifies adult hippocampal neural stem cell fate to promote neurogenesis at the cost of astrogliogenesis.

Moderate Traumatic brain injury (TBI) can result in long-lasting changes in brain function. Although frequently spared from the acute primary injury, the hippocampus becomes affected during a secondary phase that takes place hours, or even days, after TBI, contributing to cognitive deficits. The hippocampus is one of the few brain areas in the adult brain harboring native neural stem cells (NSCs) that continue to generate new neurons (neurogenesis), and to a lesser extent new astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, very little is known about how TBI may affect hippocampal astrogliogenesis. Here, we aimed to assess how TBI affects hippocampal NSCs and their subsequent commitment to the neuronal or astroglial lineages. Using a controlled cortical impact model of TBI, single cell RNA sequencing and spatial transcriptomics, we observed a cell population-specific increase in NSC-derived neuronal cells and a decrease in NSC-derived astrocytic cells. These cellular changes were associated with cell-population specific changes in gene expression and dysplasia within the dentate gyrus. Overall, our findings support the conclusion that TBI modifies adult hippocampal NSC fate to promote neurogenesis at the cost of astrogliogenesis, and highlights specific cell populations as possible targets to counteract the changes induced by TBI in the hippocampus.

neuroscience↗

bioRxiv2022

HB-EGF and zinc activate EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures

Hippocampal seizures mimicking mesial temporal lobe epilepsy (MTLE) cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive-neural stem cells, React-NSCs)) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here we, using a mouse model of MTLE, show that the epidermal growth factor receptor (EGFR) signalization pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signalization pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis. SignificanceIn mouse models of MTLE-HS, seizures cause a profound disruption of the hippocampal neurogenic niche and neurogenesis results chronically impaired, in agreement with what occurs in the human MTLE-HS hippocampus. Thus, the normal cognitive functions associated with neurogenesis are altered, but also the endogenous regenerative capacity that could compensate the high rate of neurons in the granule cell layer of the dentate gyrus. We provide here for the first time a molecular mechanism (the EGFR transduction pathway) regulating the induction of React-NSCs.

neuroscience↗