Clemastine enhances myelin formation in the striatum and medial prefrontal cortex and improves sociability in a neonatal rat hypoxic-ischemic model.

Neonatal hypoxia-ischemia (HI) results in gray and white matter injuries, leading to impairments in social behavior and severe neurological deficits. Clemastine treatment has demonstrated efficacy in alleviating behavioral deficits in various neurological disorders by improving myelin formation. It has been suggested that the medial prefrontal cortex (mPFC) and the striatum play a key role in human social behaviors.

Blockade of AR improved brain perfusion and cognitive function in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects more than 6.2 million Americans aged 65 and older, particularly women. Along with AD's main hallmarks (formation of β-amyloid plaques and tau neurofibrillary tangles), there are vascular alterations that occurs in AD pathology.

Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain.

Serum/Glucocorticoid Regulated Kinase 1 (SGK1), a serine/threonine kinase, is ubiquitous across a wide range of tissues, orchestrating numerous signaling pathways and associated with various human diseases. SGK1 has been extensively explored in diverse types of immune and inflammatory diseases, cardiovascular disorders, as well as cancer metastasis. These studies link SGK1 to cellular proliferation, survival, metabolism, membrane transport, and drug resistance.

The Impact of High-Dose Fish Oil Supplementation on Mfsd2a, Aqp4, and Amyloid-β Expression in Retinal Blood Vessels of 5xFAD Alzheimer's Mouse Model.

In patients with Alzheimer's disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) in retinal blood vessels strongly correlates with brain amyloid deposits and cognitive decline. The accumulation of Aβ in blood vessels may result from impaired transcytosis and a dysfunctional ocular glymphatic system in AD. High-dose fish oil (FO) supplementation has been shown to significantly change the expression of major facilitator superfamily domain-containing protein 2a (Mfsd2a), a key regulator of transcytosis, and Aquaporin 4 (Aqp4), an essential component of the glymphatic system in the retinas of WT mice.

Correction: Feng et al. Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase. 2024, , 633.

In the original publication [...

Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase.

Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment.

Neuroimmune Support of Neuronal Regeneration and Neuroplasticity following Cerebral Ischemia in Juvenile Mice.

Ischemic damage to the brain and loss of neurons contribute to functional disabilities in many stroke survivors. Recovery of neuroplasticity is critical to restoration of function and improved quality of life. Stroke and neurological deficits occur in both adults and children, and yet it is well documented that the developing brain has remarkable plasticity which promotes increased post-ischemic functional recovery compared with adults.

Neonatal exposure to a neuroactive steroid alters low-frequency oscillations in the subiculum.

Preclinical studies have established that neonatal exposure to contemporary sedative/hypnotic drugs causes neurotoxicity in the developing rodent and primate brains. Our group recently reported that novel neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) induced effective hypnosis in both neonatal and adult rodents but did not cause significant neurotoxicity in vulnerable brain regions such as subiculum, an output region of hippocampal formation particularly sensitive to commonly used sedatives/hypnotics. Despite significant emphasis on patho-morphological changes, little is known about long-term effects on subicular neurophysiology after neonatal exposure to neuroactive steroids.

PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury.

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI.

A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury.

Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e.

Ca3.1 T-type calcium channels are important for spatial memory processing in the dorsal subiculum.

The dorsal subiculum (dSub) is one of the key structures responsible for the formation of hippocampal memory traces but the contribution of individual ionic currents to its cognitive function is not well studied. Although we recently reported that low-voltage-activated T-type calcium channels (T-channels) are crucial for the burst firing pattern regulation in the dSub pyramidal neurons, their potential role in learning and memory remains unclear. Here we used in vivo local field potential recordings and miniscope calcium imaging in freely behaving mice coupled with pharmacological and genetic tools to address this gap in knowledge.

Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging.

Glucocorticoids are the most potent anti-inflammatory agents known. Limited in vivo data are available to characterize the mechanism underlying their cognitive side effects and transient occurrence of steroid psychosis. Cholesterol is important for proper neurotransmission and brain plasticity, and disruption of its homeostasis in the brain has been closely associated with memory decline during aging and in age-related neurodegenerative disorders.

Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of mortality, disability, and long-term care burden in the United States, with women comprising the majority of AD diagnoses. While AD-related dementia is associated with tau and amyloid beta accumulation, concurrent derangements in cerebral blood flow have been observed alongside these proteinopathies in humans and rodent models. The homeostatic production of nitric oxide synthases (NOS) becomes uncoupled in AD which leads to decreased NO-mediated vasodilation and oxidative stress via the production of peroxynitrite (ONOO-∙) superoxide species.

Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging-The Effects of Long-Term Food Restriction.

Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats.

IL13Rα2 Promotes Proliferation and Outgrowth of Breast Cancer Brain Metastases.

Purpose: The survival of women with brain metastases (BM) from breast cancer remains very poor, with over 80% dying within a year of their diagnosis. Here, we define the function of IL13Rα2 in outgrowth of breast cancer brain metastases (BCBM) and , and postulate IL13Rα2 as a suitable therapeutic target for BM.

Experimental Design: We performed IHC staining of IL13Rα2 in BCBM to define its prognostic value.

Neonatal Ketamine Alters High-Frequency Oscillations and Synaptic Plasticity in the Subiculum But Does not Affect Sleep Macrostructure in Adolescent Rats.

Exposure to sedative/hypnotic and anesthetic drugs, such as ketamine, during the critical period of synaptogenesis, causes profound neurotoxicity in the developing rodent and primate brains and is associated with poor cognitive outcomes later in life. The subiculum is especially vulnerable to acute neurotoxicity after neonatal exposure to sedative/hypnotic and anesthetic drugs. The subiculum acts as a relay center between the hippocampal complex and various cortical and subcortical brain regions and is also an independent generator of gamma oscillations.

Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABA currents, but are not neurotoxic to the developing rat brain.

Background: The most currently used general anaesthetics are potent potentiators of γ-aminobutyric acid A (GABA) receptors and are invariably neurotoxic during the early stages of brain development in preclinical animal models. As causality between GABA potentiation and anaesthetic-induced developmental neurotoxicity has not been established, the question remains whether GABAergic activity is crucial for promoting/enhancing neurotoxicity. Using the neurosteroid analogue, (3α,5α)-3-hydroxy-13,24-cyclo-18,21-dinorchol-22-en-24-ol (CDNC24), which potentiates recombinant GABA receptors, we examined whether this potentiation is the driving force in inducing neurotoxicity during development.

Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.

Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease.

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid.

The ventral tegmental area (VTA) is a midbrain region highly involved in motivation and reward. A large body of work has investigated synaptic plasticity and ion channel excitability in this area, which has strong implication in drug abuse. We recently provided electrophysiological and pharmacological evidence that the Ca3.

Sevoflurane Exposure Results in Sex-Specific Transgenerational Upregulation of Target IEGs in the Subiculum.

Large body of animal work and emerging clinical findings have suggested that early exposure to anesthetics may result in increased risk of learning disabilities and behavioral impairments. Recent studies have begun to investigate anesthesia-induced epigenetic modifications to elucidate their role in behavioral and neurodevelopmental abnormalities. Here we examine sevoflurane-induced transgenerational modifications of subicular neuronal DNA methylation and expression of immediate early genes (IEGs), arc and junB, crucial to synaptic plasticity and normal neuronal development.

Novel neurosteroid hypnotic blocks T-type calcium channel-dependent rebound burst firing and suppresses long-term potentiation in the rat subiculum.

Background: Hypnotics and general anaesthetics impair memory by altering hippocampal synaptic plasticity. We recently reported on a neurosteroid analogue with potent hypnotic activity [(3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile; 3β-OH], which does not cause developmental neurotoxicity in rat pups. Here, we investigated the effects of 3β-OH on neuronal excitability in the subiculum, the major output structure of the hippocampal formation, and synaptic plasticity at two key hippocampal synapses in juvenile rats.

Selective inhibition of Ca3.2 channels reverses hyperexcitability of peripheral nociceptors and alleviates postsurgical pain.

Pain-sensing sensory neurons of the dorsal root ganglion (DRG) can become sensitized or hyperexcitable in response to surgically induced peripheral tissue injury. We investigated the potential role and molecular mechanisms of nociceptive ion channel dysregulation in acute pain conditions such as those resulting from skin and soft tissue incision. We used selective pharmacology, electrophysiology, and mouse genetics to link increased current densities arising from the Ca3.

Ca3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons.

Recent data have implicated voltage-gated calcium channels in the regulation of the excitability of neurons within the mesolimbic reward system. While the attention of most research has centered on high voltage L-type calcium channel activity, the presence and role of the low voltage-gated T-type calcium channel (T-channels) has not been well explored. Hence, we investigated T-channel properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type (WT) rats and mice, Ca3.

A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats.

The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment.