Neuroscience
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Estrogens and progesterone can have rapid effects on neuronal function and can modify the use of spatial navigation strategies dependent upon the prefrontal cortex, striatum, and hippocampus. Here, we assessed the effects of 17β-estradiol (E2), progesterone, and its metabolite allopregnanolone, on evoked excitatory postsynaptic potentials in the infralimbic region of the female rat prefrontal cortex. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of layer I were first characterized by recording responses at multiple depths between the cortical surface and the underlying white matter. ⋯ The effects of progesterone were not blocked by the nuclear progesterone receptor antagonist RU486 (1 µM). Both progesterone and allopregnanolone are known to activate membrane progesterone receptors, and we found that the membrane progesterone receptor agonist Org OD 02-0 facilitated EPSPs, and also occluded further increases induced by either progesterone or allopregnanolone. These results provide evidence that both progesterone and allopregnanolone facilitate synaptic responses in layer I of the infralimbic cortex by activating membrane progesterone receptors.
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We examined DA activity in the medial prefrontal cortex (mPFC) and nucleus accumbens core (NAcc) in two Different Rat Models of Attention-Deficit/Hyperactivity Disorder: Spontaneously Hypertensive Rats (SHR) Versus Lphn3 Knockout Rats. We examined baseline stimulation-evoked phasic DA release, half-life, and DA autoreceptor (DAR) functioning in the mPFC and NAcc, as well as the response to nomifensine (10 mg/kg, IP), a DA transporter (DAT) blocker, on these measures in the NAcc. Both rat models were hypodopaminergic, with notable regional and mechanistic differences. ⋯ Lphn3 KOs displayed increased DA half-life in the mPFC compared with Lphn3 WT rats, an indication of decreased DAT reuptake, with no differences in the NAcc. DAT blockade by nomifensine had a similar effect on DA release in the NAcc of SHRs and WKYs, but increased DA release in the NAcc of Lphn3 KOs to a greater extent than in WTs. These results suggest that the efficacy of pharmacotherapies used to treat externalizing disorders such as ADHD and/or SUD, likely differ between SHRs and Lphn3 KO rats.
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This review explores the mechanisms and treatment strategies of ischemic stroke, a leading cause of morbidity and mortality worldwide. Ischemic stroke results from the obstruction of blood flow to the brain, leading to significant neurological impairment. The paper categorizes ischemic stroke into subtypes based on etiology, including cardioembolism and large artery atherosclerosis, and discusses the challenges of current therapeutic approaches. ⋯ The review highlights the promise of acupuncture, which offers neuroprotective benefits by promoting cerebral ischemic tolerance and neural regeneration. Integrating acupuncture with conventional treatments may enhance patient outcomes. Emphasis is placed on understanding the pathophysiology to develop targeted therapies that mitigate neuronal damage and enhance recovery.
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Peripheral optogenetics is an emerging neuromodulation technique that regulates the activity of the nervous system outside the brain through the expression of photosensitive proteins and the application of photic stimulation. This article reviews recent advances in applying optogenetics to the spinal cord and peripheral nerves, offering a comprehensive understanding of the functions and regulatory mechanisms of the peripheral nervous system through the modulation of specific neuronal activities. ⋯ Despite current challenges, such as operability, effectiveness, and selective neuron targeting, peripheral optogenetics holds significant potential for advancing neuromodulation. Continued research and technological innovations will further expand its role, offering new possibilities for understanding and treating disorders involving the peripheral nervous system.
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Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. ⋯ The lithium treatment also significantly reduced ROS levels in the stressed control neurons. These findings reveal a positive association between lithium treatment, REST restoration, and oxidative stress reduction, suggesting that repurposing lithium could contribute to developing therapeutic strategies for DS neuropathologies. This study provides novel insights into DS molecular mechanisms and highlights the potential of lithium as a targeted intervention for improving neuronal function in DS.