Neuroscience
-
The subplate is a transient layer between the cortical plate and intermediate zone in the developing cortex. Thalamo-cortical axons form temporary synapses on subplate neurons (SPns) before invading the cortical plate. Neuronal activity within the subplate is of critical importance for the development of neocortical circuits and architecture. ⋯ In the presence of SNAP-5114 CGP55845 did not influence GABAergic transmission, indicating that GABABRs are not activated any longer. We conclude that in the subplate GAT-2/3 operates in reverse mode. GABA released via GAT-2/3 activates presynaptic GABABRs on GABAergic synapses and tonically inhibits GABAergic inputs on SPns.
-
Minocycline, a second-generation tetracycline alleviates neuro-inflammation and protects the blood-brain barrier (BBB) in ischemia stroke. However, the effect of minocycline in hypoxia-induced BBB damage is unclear. Here, we have investigated the effect of minocycline under hypoxia and explored its possible underlying mechanisms. ⋯ Minocycline inhibits HIF-1α-mediated cellular responses and protects BBB integrity through SIRT-3/PHD-2 pathway, proving to be a potential drug for the prevention and treatment of hypoxic brain injuries.
-
Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). ⋯ Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood.
-
N-methyl-d-aspartate receptors (NMDARs) have been known to be regulated by various receptor tyrosine kinases. Activation of epidermal growth factor receptor (EGFR) specifically increases NMDAR-mediated currents and enhances long-term potentiation (LTP) in the hippocampus. However, the mechanism through which EGFR regulates NMDARs remains to be elucidated. ⋯ EGFR blockade with a specific antagonist BIBX-1382 attenuated an increase of GluN2B in the postsynaptic density during high-frequency stimulation (HFS)-induced LTP. Moreover, BIBX blockade significantly impaired HFS-induced LTP. In conclusion, our findings suggest that EGFR signaling upregulates NMDARs through modification of the GluN2B subunit, and is required for HFS-induced LTP in the hippocampus.
-
Human age-related retinal diseases, such as age-related macular degeneration (AMD), are intimately associated with decreased tissue oxygenation and hypoxia. Different antioxidants have been investigated to reverse AMD. In the present study, we describe the antioxidant 17β-estradiol (βE2) and investigate its protective effects on retinal neurons. ⋯ Taken together, these observations suggest that βE2 exerts antioxidative effects following light-induced retinal degeneration potentially via NRF2 activation. This protective mechanism may depend on two pathways: a rapid, non-genomic-type PI3K/AKT response, and a genomic-type ER-dependent response. Our data provide evidence that βE2 is a potentially effective in the treatment of retinal degeneration diseases.