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cerebral cholinergic function

Daniel Zaldivar, Alexander Rauch, Nikos K Logothetis, Jozien Goense
Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays...
December 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Raymond Wong, Nikolett Lénárt, Laura Hill, Lauren Toms, Graham Coutts, Bernadett Martinecz, Eszter Császár, Gábor Nyiri, Athina Papaemmanouil, Ari Waisman, Werner Müller, Markus Schwaninger, Nancy Rothwell, Sheila Francis, Emmanuel Pinteaux, Adam Denes, Stuart M Allan
The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed (fl/fl ) mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier (BBB) breakdown (53%) and neurological deficit (40%) compared to vehicle-treated or control (IL-1R1fl/fl ) mice...
November 16, 2018: Brain, Behavior, and Immunity
Sun-Ho Han, Jong-Chan Park, Min Soo Byun, Dahyun Yi, Jun Ho Lee, Dong Young Lee, Inhee Mook-Jung
Cerebral β-amyloid (cAβ) deposition and cholinergic dysfunction have been considered as major pathological and functional hallmarks of Alzheimer's disease (AD). Acetylcholinesterase (AChE) is one of the major cholinergic enzymes, and there is no report to show the relationship between cAβ accumulation and peripheral AChE alteration in early stage of AD pathogenesis. Recent studies demonstrate that cAβ starts to deposit 15-20 years ahead of symptomatic appearance and this preclinical AD is important for early diagnosis of disease...
September 8, 2018: Neurobiology of Aging
Zhiping Li, Xia Chen, Yongfeng Zhang, Xin Liu, Chunyue Wang, Lesheng Teng, Di Wang
This study explores the neuro-protective effects of Amanita caesarea polysaccharides (ACPS), obtained by 80% alcohol precipitation of water extract and purified using a DEAE-52 cellulose anion exchange column, related to antioxidant activity. A 3-h pre-treatment of ACPS prior to l‑glutamic acid (l‑Glu) co-exposure reversed the decreased cell viability, inhibited apoptosis, suppressed the accumulation of intracellular reactive oxygen species and restored mitochondrial membrane potential in HT22 cells. Compared to l‑Glu-exposed cells, ACPS enhanced the nuclear levels of NF-E2p45-related factor 2 (Nrf2), reduced the cytoplasmic levels of Nrf2 and cytochrome C, suppressed the expression of Kelch-like ECH-associated protein 1, and enhanced the expression of heme oxygenase‑1, superoxide dismutase 1 and cysteine ligase catalytic subunit...
January 2019: International Journal of Biological Macromolecules
Aminu Imam, Adhil Bhagwandin, Moyosore S Ajao, Amadi O Ihunwo, Kjell Fuxe, Paul R Manger
Here, we used a range of immunohistochemical stains, focussing on tyrosine hydroxylase and dopamine-β-hydroxylase, to show that within the pons of tree pangolins clusters of noradrenergic neurons are present. No noradrenergic neurons were observed in the pontine periventricular gray matter (A6 and A4 groups missing), with all noradrenergic neurons being found within the pontine tegmentum (A7 and A5 groups). The tree pangolin is unique in lacking the locus coeruleus (A6) cell group observed in all vertebrates previously studied; however, noradrenergic axons and terminal networks were found throughout the cerebral cortex...
November 1, 2018: Journal of Comparative Neurology
Hyunjo Kim
The prevalent cause of dementia - Alzheimer's disease (AD) is characterized by an early cholinergic deficit that is in part responsible for the cognitive deficits (especially memory and attention defects). Prolonged AD leads to moderate-to-severe AD, which is one of the leading causes of death. Placebo-controlled, randomized clinical trials have shown significant effects of Acetyl cholin esterase inhibitors (ChEIs) on function, cognition, activities of daily living (ADL) and behavioral symptoms in patients...
2018: Bioinformation
Xiao-Qiao Zhang, Li Li, Jiang-Tao Huo, Min Cheng, Lin-Hong Li
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown. In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were administered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1.33 T...
August 2018: Neural Regeneration Research
Arianna Casini, Rosa Vaccaro, Mattia Toni, Carla Cioni
Cholinergic systems play a role in basic cerebral functions and its dysfunction is associated with deficit in neurodegenerative disease. Mechanisms involved in human brain diseases, are often approached by using fish models, especially cyprinids, given basic similarities of the fish brain to that of mammals. In the present paper, the organization of central cholinergic systems have been described in the cyprinid Cyprinus carpio, the common carp, by using specific polyclonal antibodies against ChAT, the synthetic enzyme of acetylcholine, that is currently used as a specific marker for cholinergic neurons in all vertebrates...
July 24, 2018: European Journal of Histochemistry: EJH
Gülseren Büyükşerbetçi, Esen Saka, Kader Karli Oğuz, Rahşan Göçmen, Ethem Murat Arsava, Mehmet Akif Topçuoğlu
Introduction: Contribution of cerebral microbleeds (CMBs) on cognitive dysfunctions in elderly patients with otherwise asymptomatic white matter lesions (WMLs) is not well-documented. Methods: MRI parameters of cerebral atrophy, CMBs and WMLs were herein analyzed in relation to global and main domains (attention, executive, memory, visuospatial, language) of cognitive function. Eighty-five patients older than 50, without neurodegenerative/cerebrovascular disease, but had CMBs were recruited from 2562 with T2*-gradient-echo MR imaging during one-year period...
March 2018: Noro Psikiyatri Arsivi
Juliana Tonietto Domingues, Carolinne Sayury Wajima, Patricia Acordi Cesconetto, Eduardo Benedetti Parisotto, Elisa Winkelmann-Duarte, Karin Dos Santos, Najla Saleh, Fabíola Branco Filippin-Monteiro, Guilherme Razzera, Fátima Regina Mena Barreto Silva, Regina Pessoa-Pureur, Ariane Zamoner
In this study, we used an experimental model of congenital hypothyroidism to show that deficient thyroid hormones (TH) disrupt different neurochemical, morphological and functional aspects in the cerebral cortex of 15-day-old offspring. Our results showing decreased glutamine synthetase (GS) activity and Ca2+ overload in the cerebral cortex of hypothyroid pups suggest misregulated glutamate metabolism associated with developmentally induced TH deficiency. The 14 C-MeAIB accumulation indicates upregulated System A activity and glutamine uptake by neurons...
July 18, 2018: Molecular and Cellular Endocrinology
Hee-Jun Rho, Jae-Hyun Kim, Seung-Hee Lee
Cortical processing is dynamically modulated by different neuromodulators. Neuromodulation of the cerebral cortex is crucial for maintaining cognitive brain functions such as perception, attention and learning. However, we do not fully understand how neuromodulatory projections are organized in the cerebral cortex to exert various functions. The basal forebrain (BF) cholinergic projection and the locus coeruleus (LC) noradrenergic projection are well-known neuromodulatory projections to the cortex. Decades of studies have identified anatomical and physiological characteristics of these circuits...
2018: Frontiers in Neural Circuits
Xuyan Jin, Dong Kyu Kim, Tae-Ryong Riew, Hong Lim Kim, Mun-Yong Lee
The 78-kDa glucose-regulated protein (GRP78), a chaperone protein located in the endoplasmic reticulum (ER), has been reported to have neuroprotective effects in the injured central nervous system. Our aim was to examine the expression profiles and subcellular distributions of GRP78 and its association with the neuroglial reaction in the rat striatum after transient, focal cerebral ischemia. In sham-operated rats, constitutive, specific immunoreactivity for GRP78 was almost exclusively localized to the rough ER of striatal neurons, with none in the resting, ramified microglia or astrocytes...
July 2018: Neurochemical Research
Jong Min Kim, Seon Kyeong Park, Jin Yong Kang, Su Bin Park, Seul Ki Yoo, Hye Ju Han, Chul-Woo Kim, Uk Lee, Sea-Hyun Kim, Ho Jin Heo
This study was conducted to assess the antioxidant capacity and protective effect of the ethyl acetate fraction from persimmon ( Diospyros kaki ) (EFDK) on H₂O₂-induced hippocampal HT22 cells and trimethyltin chloride (TMT)-induced Institute of Cancer Research (ICR) mice. EFDK had high antioxidant activities and neuroprotective effects in HT22 cells. EFDK ameliorated behavioral and memory deficits in Y-maze, passive avoidance and Morris water maze tests. Also, EFDK restored the antioxidant system by regulating malondialdehyde (MDA), superoxide dismutase (SOD) and reduced gluthathione (GSH), and the cholinergic system by controlling the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity and expression...
May 17, 2018: International Journal of Molecular Sciences
Andrew C Peterson, Chiang-Shan R Li
Noradrenergic dysfunction contributes to cognitive impairment in Alzheimer's Disease (AD) and Parkinson's Disease (PD). Conventional therapeutic strategies seek to enhance cholinergic and dopaminergic neurotransmission in AD and PD, respectively, and few studies have examined noradrenergic dysfunction as a target for medication development. We review the literature of noradrenergic dysfunction in AD and PD with a focus on human imaging studies that implicate the locus coeruleus (LC) circuit. The LC sends noradrenergic projections diffusely throughout the cerebral cortex and plays a critical role in attention, learning, working memory, and cognitive control...
2018: Frontiers in Aging Neuroscience
Jun-De Zhu, Jun-Jie Wang, Xian-Hu Zhang, Yan Yu, Zhao-Sheng Kang
Panax ginseng is a slow-growing perennial plant. Panax ginseng extract has numerous biological activities, including antitumor, anti-inflammatory and antistress activities. Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment. In this study, we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion, a well-known model of vascular dementia. The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract...
April 2018: Neural Regeneration Research
Shigeki Hirano, Hitoshi Shinotoh, Hitoshi Shimada, Tsuneyoshi Ota, Koichi Sato, Noriko Tanaka, Ming-Rong Zhang, Makoto Higuchi, Kiyoshi Fukushi, Toshiaki Irie, Satoshi Kuwabara, Tetsuya Suhara
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. OBJECTIVE: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age...
2018: Journal of Alzheimer's Disease: JAD
Anand M Bokare, Mandar Bhonde, Rajan Goel, Yogendra Nayak
RATIONALE AND OBJECTIVES: 5-HT6 receptors are mainly expressed in brain areas associated with learning and memory. Several studies have reported procognitive effects of both 5-HT6 agonist and antagonists. However, the exact mechanism 5-HT6 receptor modulation has not been properly studied especially in the context of cholinergic functions, cerebral blood flow (CBF), brain-derived neural factor (BDNF), oxidative stress, and behavioral changes. METHODS: In the present study, memory impairment was induced in albino Wistar rats by two doses of intracerebroventricular (ICV) injection of streptozotocin (STZ, 3 mg/kg) on first and third day...
May 2018: Psychopharmacology
Yang Liu, Yan-Hong Dong, Pei-Yuan Lyu, Wei-Hong Chen, Rui Li
Objective: Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD) is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources: We searched and scanned the PubMed database for recently published literatures up to December 2017...
March 5, 2018: Chinese Medical Journal
Baojie Zhu, Huiting Cao, Limin Sun, Bo Li, Liwei Guo, Jinao Duan, Huaxu Zhu, Qichun Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian Jie-Du decoction (HLJDD), a traditional formula of Chinese medicine constituted with Rhizoma Coptidis, RadixScutellariae, CortexPhellodendri amurensis and Fructus Gardeniae, exhibits unambiguous therapeutic effect on cerebral ischemia via multi-targets action. Further investigation, however, is still required to explore the relationship between those mechanisms and targets through system approaches. MATERIALS AND METHODS: Rats of cerebral ischemia were completed by middle cerebral artery occlusion (MCAO) with reperfusion...
April 24, 2018: Journal of Ethnopharmacology
Joshua Obermayer, Matthijs B Verhoog, Antonio Luchicchi, Huibert D Mansvelder
Acetylcholine (ACh) signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence...
2017: Frontiers in Neural Circuits
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