Crocin mitigated cognitive impairment and brain molecular alterations induced by different intensities of prenatal hypoxia in neonatal rats

Background. Perinatal hypoxia is a universal cause of death and neurological deficits in neonates worldwide. Activation of microglial NADPH oxidase 2 (NOX2) leads to oxidative stress and neuroinflammation, which may contribute to hypoxic damage in the developing brain. Dexmedetomidine has been reported to exert potent neuroprotection in several neurological diseases, but the mechanism remains unclear. We investigated whether dexmedetomidine acts through microglial NOX2 to reduce neonatal hypoxic brain damage. Methods. The potential role of microglial NOX2 in dexmedetomidine-mediated alleviation of hypoxic damage was evaluated in cultured BV2 microglia and neonatal rats subjected to hypoxia. In vivo, neonatal rats received dexmedetomidine (25 μg/kg, i.p.) 30 min before or immediately after hypoxia (5% O2, 2 h). Apocynin-mediated NOX inhibition and lentivirus-mediated NOX2 overexpression were applied to further assess the involvement of microglial NOX2 activation. Results. Pre- or posttreatment with dexmedetomidine alleviated hypoxia-induced cognitive impairment, restored damaged synapses, and increased postsynaptic density-95 and synaptophysin protein expression following neonatal hypoxia. Importantly, dexmedetomidine treatment suppressed hypoxia-induced microglial NOX2 activation and subsequent oxidative stress and the neuroinflammatory response, as reflected by reduced 4-hydroxynonenal and ROS accumulation, and decreased nuclear NF-κB p65 and proinflammatory cytokine levels in cultured BV2 microglia and the developing hippocampus. In addition, treating primary hippocampal neurons with conditioned medium (CM) from hypoxia-activated BV2 microglia resulted in neuronal damage, which was alleviated by CM from dexmedetomidine-treated microglia. Moreover, the neuroprotective effect of dexmedetomidine was reversed in NOX2-overexpressing BV2 microglia and diminished in apocynin-pretreated neonatal rats. Conclusion. Dexmedetomidine targets microglial NOX2 to reduce oxidative stress and neuroinflammation and subsequently protects against hippocampal synaptic loss following neonatal hypoxia.

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NF-κB signaling pathway inhibition suppresses hippocampal neuronal apoptosis and cognitive impairment via RCAN1 in neonatal rats with hypoxic-ischemic brain damage

Cell Cycle ◽

10.1080/15384101.2019.1608128 ◽

2019 ◽

Vol 18 (9) ◽

pp. 1001-1018 ◽

Cited By ~ 3

Author(s):

Hua Fang ◽

Hua-Feng Li ◽

Miao Yang ◽

Ren Liao ◽

Ru-Rong Wang ◽

...

Keyword(s):

Cognitive Impairment ◽

Signaling Pathway ◽

Brain Damage ◽

Neuronal Apoptosis ◽

Neonatal Rats ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Pathway Inhibition

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Cognitive impairment in neuromuscular diseases: A systematic review

Neurology International ◽

10.4081/ni.2018.7473 ◽

2018 ◽

Vol 10 (2) ◽

Cited By ~ 5

Author(s):

Marco Orsini ◽

Ana Carolina Andorinho de F. Ferreira ◽

Anna Carolina Damm de Assis ◽

Thais Magalhães ◽

Silmar Teixeira ◽

...

Keyword(s):

Cognitive Impairment ◽

Genetic Analysis ◽

Motor Neuron ◽

Case Reports ◽

Experimental Studies ◽

Neuromuscular Diseases ◽

Mitochondrial Disorders ◽

Motor Neuron Diseases ◽

Fiber Damage ◽

Molecular Alterations

Neuromuscular diseases are multifactorial pathologies characterized by extensive muscle fiber damage that leads to the activation of satellite cells and to the exhaustion of their pool, with consequent impairment of neurobiological aspects, such as cognition and motor control. To review the knowledge and obtain a broad view of the cognitive impairment on Neuromuscular Diseases. Cognitive impairment in neuromuscular disease was explored; a literature search up to October 2017 was conducted, including experimental studies, case reports and reviews written in English. Keywords included Cognitive Impairment, Neuromuscular Diseases, Motor Neuron Diseases, Dystrophinopathies and Mitochondrial Disorders. Several cognitive evaluation scales, neuroimaging scans, genetic analysis and laboratory applications in neuromuscular diseases, especially when it comes to the Motor Neuron Diseases, Dystrophinopathies and Mitochondrial Disorders. In addition, organisms model using rats in the genetic analysis and laboratory applications to verify the cognitive and neuromuscular impacts. Several studies indicate that congenital molecular alterations in neuromuscular diseases promote cognitive dysfunctions. Understanding these mechanisms may in the future guide the proper management of the patient, evaluation, establishment of prognosis, choice of treatment and development of innovative interventions such as gene therapy.

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Anxiety, Impaired Social and Aggressive Behaviour Correlates With Cognitive Decline Accompanied by Molecular Alterations in Older SAMP8 Males

10.20944/preprints202101.0162.v1 ◽

2021 ◽

Author(s):

Foteini Vasilopoulou ◽

Júlia Companys-Alemany ◽

Anna-Maria Canudas ◽

Verónica Palomera-Ávalos ◽

Daniel Ortuño-Sahagún ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Deficits ◽

Psychological Symptoms ◽

Inbred Mouse ◽

Accelerated Aging ◽

Molecular Alterations ◽

Cognitive States ◽

Underlying Mechanisms ◽

The University ◽

Senescence Accelerated Mouse

Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive and cognitive states as well as molecular alterations and their relationship, demonstrating the AD-like symptoms presented in older SAMP8 males. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in three of the most important neurotrophins, such as NT3, BDNF, and NGF as well as their receptors TrkA and TrkB, were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin alterations, cognitive impairment and neuropsychiatric disorders (ND).

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Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer’s disease neuropathology in APPSwe/PS1A246E transgenic mice

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2012.06.012 ◽

2013 ◽

Vol 34 (3) ◽

pp. 663-678 ◽

Cited By ~ 31

Author(s):

Xin Zhang ◽

Lixi Li ◽

Xiaojie Zhang ◽

Wenjie Xie ◽

Liang Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Transgenic Mice ◽

Prenatal Hypoxia

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Review for "Expression profiling of precuneus layer III cathepsin D‐immunopositive pyramidal neurons in mild cognitive impairment and Alzheimer's disease: Evidence for neuronal signaling vulnerability"

10.1002/cne.24929/v2/review1 ◽

2020 ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Expression Profiling ◽

Cathepsin D ◽

Pyramidal Neurons ◽

Neuronal Signaling

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Ultrastructural Localization of Acetylcholinesterase in the Arcuate Nucleus and Median Eminence of the Rat

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079644 ◽

1977 ◽

Vol 35 ◽

pp. 440-441

Author(s):

K.A. Carson ◽

C.B. Nemeroff ◽

M.S. Rone ◽

J.S. Kizer ◽

J.S. Hanker

Keyword(s):

Choline Acetyltransferase ◽

Median Eminence ◽

Arcuate Nucleus ◽

Cholinergic Neurons ◽

Ultrastructural Localization ◽

Male Rats ◽

Neonatal Rats ◽

Good Marker ◽

Chemical Studies ◽

High Doses

Biochemical, physiological, pharmacological, and more recently enzyme histo- chemical data have indicated that cholinergic circuits exist in the hypothalamus. Ultrastructural correlates of these pathways such as acetylcholinesterase (AchE) positive neurons in the arcuate nucleus (ARC) and stained terminals in the median eminence (ME) have yet to be described. Initial studies in our laboratories utilizing chemical lesioning and microdissection techniques coupled with microchemical and light microscopic enzyme histo- chemical studies suggested the existence of cholinergic neurons in the ARC which project to the ME (1). Furthermore, in adult male rats with Halasz deafferentations (hypothalamic islands composed primarily of the isolated ARC and the ME) choline acetyltransferase (ChAc) activity, a good marker for cholinergic neurons, was not significantly reduced in the ME and was only somewhat reduced in the ARC (2). Treatment of neonatal rats with high doses of monosodium 1-glutamate (MSG) results in a lesion largely restricted to the neurons of the ARC.

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