Ferroptosis and cognitive impairment: Unraveling the link and potential therapeutic targets.

Neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, share key characteristics, notably cognitive impairment and significant cell death in specific brain regions. Cognition, a complex mental process allowing individuals to perceive time and place, is disrupted in these conditions. This consistent disruption suggests the possibility of a shared underlying mechanism across all neurodegenerative diseases.

Mitochondrial plasticity and synaptic plasticity crosstalk; in health and Alzheimer's disease.

Synaptic plasticity is believed to underlie the cellular and molecular basis of memory formation. Mitochondria are one of the main organelles involved in metabolism and energy maintenance as plastic organelles that change morphologically and functionally in response to cellular needs and regulate synaptic function and plasticity through multiple mechanisms, including ATP generation, calcium homeostasis, and biogenesis. An increased neuronal activity enhances synaptic efficiency, during which mitochondria's spatial distribution and morphology change significantly.

Involvement of relaxin-family peptide-3 receptor (RXFP3) in the ventral dentate gyrus of the hippocampus in spatial and fear memory in rats.

The neuropeptide relaxin-3 and its cognate receptor, relaxin family peptide-3 receptors (RXFP3), have been implicated in modulating learning and memory processes, but their specific roles remain unclear. This study utilized behavioral and molecular approaches to investigate the effects of putatively reversible blockade of RXFP3 in the ventral dentate gyrus (vDG) of the hippocampus on spatial and fear memory formation in rats. Male Wistar rats received bilateral vDG cannula implantation and injections of the RXFP3 antagonist, R3(BΔ23-27)R/I5 (400 ng/0.

Hepatic Acyl CoA Oxidase1 Inhibition Modifies Brain Lipids and Electrical Properties of Dentate Gyrus.

Introduction: Peroxisomes are essential organelles in lipid metabolism. They contain enzymes for β-oxidation of very long-chain fatty acids (VLCFA) that cannot be broken down in mitochondria. Reduced expression in hepatic acyl-CoA oxidase 1 (ACOX1), a peroxisome β-oxidation enzyme, followed by modification of the brain fatty acid profile has been observed in aged rodents.

Neuroprotective Effects of Ferrostatin and Necrostatin Against Entorhinal Amyloidopathy-Induced Electrophysiological Alterations Mediated by voltage-gated Ca Channels in the Dentate Gyrus Granular Cells.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the main form of dementia. Abnormal deposition of amyloid-beta (Aβ) peptides in neurons and synapses cause neuronal loss and cognitive deficits. We have previously reported that ferroptosis and necroptosis were implicated in Aβ neurotoxicity, and their specific inhibitors had attenuating effects on cognitive impairment induced by Aβ neurotoxicity.

Role of amyloid beta (25-35) neurotoxicity in the ferroptosis and necroptosis as modalities of regulated cell death in Alzheimer's disease.

Neuronal cell death as a prominent pathological feature contributes to cognitive decline and memory loss in Alzheimer's disease. We investigated the role of two forms of cell death pathways, ferroptosis and necroptosis, and their interactions following entorhinal cortex (EC) amyloidopathy. The Aβ was bilaterally injected into the rat's EC, and Morris Water Maze was applied to determine spatial performance one week after Aβ injection.

Phosphonate analog of 2-oxoglutarate regulates glutamate-glutamine homeostasis and counteracts amyloid beta induced learning and memory deficits in rats.

Background: Metabolic alteration is a mainstream concept underlying the cognitive decline in neurodegenerative disorders including Alzheimer's disease (AD). Mitochondrial enzyme α-ketoglutarate dehydrogenase complex (α-KGDHC) seems to play a dual-edged sword role in cytotoxic insult. Here, using succinyl phosphonate (SP), a specific α-KGDHC inhibitor, we aimed to examine its potential action on AD progression.

Kisspeptin-13 prevented the electrophysiological alterations induced by amyloid-beta pathology in rat: Possible involvement of stromal interaction molecules and pCREB.

Alzheimer's disease (AD) is a progressive neurological disease that slowly causing memory impairments with no effective treatment. We have recently reported that kisspeptin-13 (KP-13) ameliorates Aβ toxicity-induced memory deficit in rats. Here, the possible cellular impact of kisspeptin receptor activation in a rat model of the early stage AD was assessed using whole-cell patch-clamp recording from CA1 pyramidal neurons and molecular approaches.

Optogenetic stimulation of entorhinal cortex reveals the implication of insulin signaling in adult rat's hippocampal neurogenesis.

Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood.

Oxytocin Prevents the Development of 3-NP-Induced Anxiety and Depression in Male and Female Rats: Possible Interaction of OXTR and mGluR2.

Huntington disease (HD) is a progressive neurological disorder with dominant motor symptoms. It also has psychiatric manifestations, like anxiety and depression, that can emerge themselves before motor symptoms and impose a major burden on patients. Oxytocin (OXT) is a newly emerged treatment for disorders like autism and schizophrenia and recently is using to alleviate depression and anxiety.

Overexpression of protein kinase Mζ in the hippocampus mitigates Alzheimer's disease-related cognitive deficit in rats.

Accumulation of amyloid beta (Aβ) soluble forms in the cerebral parenchyma is the mainstream concept underlying memory deficit in the early phase of Alzheimer's disease (AD). PKMζ plays a critical role in the maintenance of long-term memory. Yet, the role of this brain-specific enzyme has not been addressed in AD.

Kisspeptin-13 Improves Spatial Memory Consolidation and Retrieval against Amyloid-β Pathology.

It has been shown that brain glucose metabolism impairment, obesity, and diabetes could lead to cognitive decline and Alzheimer's disease (AD) pathogenesis. Kisspeptin (KP) a G-protein coupled receptor neuropeptide, has been suggested as a link between energy balance and reproduction. Some studies have shown that the attenuation of KP signaling decreases metabolism and energy expenditure.

Individual Subnuclei of the Rat Anterior Thalamic Nuclei Differently affect Spatial Memory and Passive Avoidance Tasks.

The role of the anterior thalamic nuclei (ATN) has been proven in different learning and memory tasks. The ATN consist of three main subnuclei, the anterodorsal (AD), anteroventral (AV) and anteromedial (AM), which have different biological characteristics such as distinct circuitry, cell population and neurotransmitter content. The role of ATN subnuclei in learning and memory has been shown in several studies.

Measuring the Frequency-Specific Functional Connectivity Using Wavelet Coherence Analysis in Stroke Rats Based on Intrinsic Signals.

Optical intrinsic signal imaging (OISi) method is an optical technique to evaluate the functional connectivity (FC) of the cortex in animals. Already, using OISi, the FC of the cortex has been measured in time or frequency domain separately, and at frequencies below 0.08 Hz, which is not in the frequency range of hemodynamic oscillations which are able to track fast cortical events, including neurogenic, myogenic, cardiac and respiratory activities.

Oxytocin protects against 3-NP induced learning and memory impairment in rats: Sex differences in behavioral and molecular responses to the context of prenatal stress.

Learning and memory impairment manifests years before the onset of motor impairments in Huntington's disease (HD). Oxytocin (OXT), as a neurohypophyseal neuropeptide has a key role in both learning and memory. Hence, we investigated possible protective effect of OXT on instrumental fear conditioning memory impairment by 3-Nitropropionic acid (3-NP) induced HD, considering sex and prenatal stress effects.

Role of orexinergic receptors in the dentate gyrus of the hippocampus in the acquisition and expression of morphine-induced conditioned place preference in rats.

Orexinergic projections derived from the lateral hypothalamus (LH) play a crucial role in the acquisition and expression of morphine-conditioned place preference (CPP). It has been demonstrated in previous that orexinergic receptors are expressed in the dentate gyrus (DG) region of the hippocampus, which receives projections of LH orexinergic neurons. This study examined the effects of intra-DG orexin-1 (OX1) and orexin-2 (OX2) receptor antagonists on the acquisition and expression of CPP induced by morphine.

Temporary inactivation of interpeduncular nucleus impairs long but not short term plasticity in the perforant-path dentate gyrus synapses in rats.

The interconnectivity of the hippocampus, interpeduncular nucleus (IPN) and several brain structures which are involved in modulating hippocampal theta rhythm activity makes a complicated dynamic network of interconnected regions and highlights the role of IPN in the hippocampal dependent learning and memory. In the present study we aimed to address whether IPN is involved in the perforant path-dentate gyrus (PPDG) short term and long term synaptic plasticity in rats. To silent IPN transiently, lidocaine was injected through the implanted cannula above the IPN.

Involvement of orexin receptors within the hippocampal dentate gyrus in morphine-induced reinstatement in food-deprived rats.

The orexinergic system is found to cooperate in mediating stress-induced drug relapse. The orexinergic terminals innervate neurons of the hippocampal dentate gyrus (DG) which is a key structure in the maintenance and reinstatement of drug addiction. However, the specific contribution of intra-DG orexin receptors to stress-induced reinstatement has not been completely known.

Peroxisomal Malfunction Caused by Mitochondrial Toxin 3-NP: Protective Role of Oxytocin.

Peroxisomes are single membrane cell organelles with a diversity of metabolic functions. Here we studied the peroxisomal dysfunction and oxidative stress after 3-nitropropionic acid (3-NP) induced neurotoxicity and the possible protective effects of oxytocin. Adult male and female rats were subjected to OXT and/or 3-NP treatment.

Preconditioning with toll-like receptor agonists attenuates seizure activity and neuronal hyperexcitability in the pilocarpine rat model of epilepsy.

Neuroinflammation plays an important role in epileptic disorders. Toll-like receptors (TLRs) are the key signal transduction tools by which neuroinflammation may promote epileptogenesis. Depending on the stimulus nature, TLRs may engage a distinct signaling pathway.

Entorhinal cortex stimulation induces dentate gyrus neurogenesis through insulin receptor signaling.

Deep brain stimulation (DBS) has been established as a therapeutically effective method to treat pharmacological resistant neurological disorders. The molecular and cellular mechanisms underlying the beneficial effects of DBS on the brain are not yet fully understood. Beside numerous suggested mechanisms, regulation of neurogenesis is an attractive mechanism through which DBS can affect the cognitive functions.

CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: A Behavioral and Molecular Study in a Rat Model of Aβ Toxicity.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease, characterized by extracellular deposition of senile plaques, mostly amyloid β-protein (Aβ) and neuronal loss. The neuroprotective effects of erythropoietin (EPO) have been reported in some models of neurodegenerative disease, but because of its hematopoietic side effects, its derivatives lacking hematopoietic bioactivity is recommended. In this study, the neuroprotective effects of carbamylated erythropoietin-Fc (CEPO-Fc) against beta amyloid-induced memory deficit were evaluated.

Early minor stimulation of microglial TLR2 and TLR4 receptors attenuates Alzheimer's disease-related cognitive deficit in rats: behavioral, molecular, and electrophysiological evidence.

At early stages of Alzheimer's disease (AD), soluble amyloid beta (Aβ) accumulates in brain while microglia are in resting state. Microglia can recognize Aβ long after formation of plaques and release neurotoxic mediators. We examined impact of early minor activation of microglia by Toll-like receptors (TLRs) 2 and 4 agonists on Alzheimer's disease-related disturbed synaptic function and spatial memory in rats.

Reversible inactivation of interpeduncular nucleus impairs memory consolidation and retrieval but not learning in rats: A behavioral and molecular study.

The Interpedundular nucleus (IPN) is a small midbrain structure located deeply between the two cerebral peduncles. The strategic placement of this nucleus makes it a possible relay between structures involved in the modulation of hippocampal theta rhythm activity. In this study we aimed to investigate how reversible inactivation of IPN could affect the acquisition, consolidation and retrieval phases of memory in passive avoidance (PA) and Morris water maze (MWM) tasks.

Decrease of high voltage Ca currents in the dentate gyrus granule cells by entorhinal amyloidopathy is reversed by calcium channel blockade.

In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the earliest affected networks. There are some evidences indicating abnormal neuronal excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD animal model. However, the underlying mechanism leading to DG dysfunction particularly in the early phase of AD is not known.