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Molecular Neurobiology

Joanna Jaworska, Teresa Zalewska, Joanna Sypecka, Malgorzata Ziemka-Nalecz
Neonatal hypoxic-ischemic (HI) brain injury likely represents the major cause of long-term neurodevelopmental disabilities in surviving babies. Despite significant investigations, there is not yet any known reliable treatment to reduce brain damage in suffering infants. Our recent studies in an animal model of HI revealed the therapeutic potential of a histone deacetylase inhibitor (HDACi). The neuroprotective action was connected with the stimulation of neurogenesis in the dentate gyrus subgranular zone. In the current study, we investigated whether HDACi-sodium butyrate (SB)-would also lead to neurogenesis in the subventricular zone (SVZ)...
February 14, 2019: Molecular Neurobiology
Tomás R Carden, Jorge Correale, Juana M Pasquini, María Julia Pérez
Transferrin (Tf) is a glycoprotein playing a critical role in iron homeostasis and transport and distribution throughout the body and within tissues and cells. This molecule has been shown to accelerate the process of myelination and remyelination in the central nervous system (CNS) in vivo and induce oligodendroglial cell maturation in vitro. While the mechanisms involved in oligodendroglial precursor cell (OPC) differentiation have not been fully elucidated yet, our group has previously described the first molecular events taking place in OPC in response to extracellular Tf...
February 13, 2019: Molecular Neurobiology
Erin Semple, Firas Shalabi, Jennifer W Hill
The melanocortin pathway has been implicated in both metabolism and sexual function. When the melanocortin 4 receptor (MC4R) is knocked out globally, male mice display obesity, low sexual desire, and copulatory difficulties; however, it is unclear whether these phenotypes are interdependent. To elucidate the neuronal circuitry involved in sexual dysfunction in MC4R knockouts, we re-expressed the MC4R in these mice exclusively on Sim1 neurons (tbMC4RSim1 mice) or on a subset of Sim1 neurons, namely oxytocin neurons (tbMC4Roxt mice)...
February 12, 2019: Molecular Neurobiology
Muhammad Ikram, Tahir Muhammad, Shafiq Ur Rehman, Amjad Khan, Min Gi Jo, Tahir Ali, Myeong Ok Kim
Hesperetin is a bioactive flavonoid in the body, produced from hesperidin. No comprehensive studies have shown its protective effects in neurodegenerative disorders. Here, we hypothesized that hesperetin may protect the mice brain against Aβ-induced neurodegeneration. Twenty-four hours after intracerebroventricular injection of Aβ1-42, the treated group was injected hesperetin. For in vitro experiments, HT22 and BV-2 cells were used. Immunoblot, immunofluorescence, and behavioral analyses were used to evaluate the different parameters...
February 12, 2019: Molecular Neurobiology
Cosimo Prestigio, Daniele Ferrante, Pierluigi Valente, Silvia Casagrande, Ennio Albanesi, Yuchio Yanagawa, Fabio Benfenati, Pietro Baldelli
Cultured hippocampal neurons represent the most widely used experimental substrate for in vitro electrophysiological studies. Nevertheless, in most cases, the nature of neuron under study is not identified as excitatory or inhibitory, or even worse, recorded neurons are considered as excitatory because of the paucity of GABAergic interneurons. Thus, the definition of reliable criteria able to guarantee an unequivocal identification of excitatory and inhibitory cultured hippocampal neurons is an unmet need. To reach this goal, we compared the electrophysiological properties and the localization and size of the axon initial segment (AIS) of cultured hippocampal neurons, taking advantage from GAD67-GFP knock-in mice, which expressing green fluorescent protein (GFP) in gamma-aminobutyric acid (GABA)-containing cells, allowed to unambiguously determine the precise nature of the neuron under study...
February 12, 2019: Molecular Neurobiology
G Gomez, M V Escande, L M Suarez, L Rela, J E Belforte, R Moratalla, M G Murer, O S Gershanik, I R E Taravini
Using bacterial artificial chromosome-double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model of parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced by L-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated from parvalbumin (PV)-containing striatal "fast-spiking" interneurons (FSIs), the major component of a feed-forward inhibition mechanism that regulates spike timing in MSNs, in both cell types as well as the number of vesicular GABA transporter (VGAT) contacts...
February 11, 2019: Molecular Neurobiology
Annamaria Cattaneo, Veronica Begni, Chiara Malpighi, Nadia Cattane, Alessia Luoni, Carmine Pariante, Marco A Riva
Exposure to adverse events during gestation has detrimental effects on the maturation of specific brain networks, triggering changes in the expression of several stress-related mechanisms that may lead to long-lasting functional consequences, including cognitive deterioration. On these bases, the aim of the present study was to investigate the effects of early-life stress exposure on cognition and to explore potential molecular mechanisms contributing to the long-term functional impairment. We found that exposure to prenatal stress, a well-established animal model of early-life adversity, produces a significant disruption in the novel object recognition test both in male and female adult rats, although such impairment was more pronounced in females...
February 11, 2019: Molecular Neurobiology
Kr Roversi, Caren Tatiane de David Antoniazzi, L H Milanesi, H Z Rosa, M Kronbauer, D R Rossato, T Duarte, M M Duarte, Marilise E Burger
Depression is a common psychiatric disease which pharmacological treatment relieves symptoms, but still far from ideal. Tactile stimulation (TS) has shown beneficial influences in neuropsychiatric disorders, but the mechanism of action is not clear. Here, we evaluated the TS influence when applied on adult female rats previously exposed to a reserpine-induced depression-like animal model. Immediately after reserpine model (1 mg/kg/mL, 1×/day, for 3 days), female Wistar rats were submitted to TS (15 min, 3×/day, for 8 days) or not (unhandled)...
February 11, 2019: Molecular Neurobiology
Bangrong Cai, Kyung-Joo Seong, Sun-Woong Bae, Min Suk Kook, Changju Chun, Jin Ho Lee, Won-Seok Choi, Ji-Yeon Jung, Won-Jae Kim
Microglia-mediated neuroinflammatory responses are well known to inhibit neurogenesis in the dentate gyrus (DG) of the adult hippocampus, and growing evidence indicates that therapeutic intervention to suppress microglial activation could be an effective strategy for restoring the impaired neurogenesis and memory performance. In the present study, we investigated the effects of water-soluble arginyl-diosgenin analog (Arg-DG) on the adult hippocampal neurogenesis using a central LPS-induced inflammatory mice model, along with the fundamental mechanisms in vivo and in vitro using LPS-stimulated microglial BV2 cells...
February 11, 2019: Molecular Neurobiology
Fernando Castillo Díaz, Micaela A Hernandez, Tomas Capellá, Jorge H Medina
Dopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA are crucial components of a neural circuit involving the hippocampus that induces active forgetting of cocaine-associated long-term memory, while VTA and nucleus accumbens (NAc) D1R are required for its formation...
February 9, 2019: Molecular Neurobiology
John Q Wang, Limin Mao
Major depressive disorder is a chronic debilitating mental illness. Its pathophysiology at cellular and molecular levels is incompletely understood. Increasing evidence supports a pivotal role of the mitogen-activated protein kinase (MAPK), in particular the extracellular signal-regulated kinase (ERK) subclass of MAPKs, in the pathogenesis, symptomatology, and treatment of depression. In humans and various chronic animal models of depression, the ERK signaling was significantly downregulated in the prefrontal cortex and hippocampus, two core areas implicated in depression...
February 9, 2019: Molecular Neurobiology
Xiaoning Han, Qian Li, Xi Lan, Leena El-Mufti, Honglei Ren, Jian Wang
Investigators are increasingly interested in using microglial depletion to study the role of microglia under pathologic conditions. Liposome-encapsulated clodronate is commonly used to eliminate macrophage populations because it causes functionally irreversible inhibition and apoptosis once phagocytized by macrophages. Recent studies have shown that microglia can be depleted in disease models by injecting clodronate liposomes into the brain parenchyma. However, it is unclear whether intracerebral administration of clodronate liposomes is a practical method of eliminating microglia under physiologic conditions or whether microglial depletion induces damage to other brain cells...
February 8, 2019: Molecular Neurobiology
Longfei Li, Yanli Jiang, Wen Hu, Yunn Chyn Tung, Chunling Dai, Dandan Chu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Microtubule-associated protein tau in Alzheimer's disease (AD) brain is hyperphosphorylated, truncated, and aggregated into neurofibrillary tangles. Oligomeric and hyperphosphorylated tau (Oligo-tau) isolated from AD brain captures and templates normal tau into filaments both in vitro and in vivo; this prion-like activity is believed to be responsible for the progression of neurofibrillary pathology in AD. The 3xTg-AD mouse model develops both Aβ and tau pathologies and thus gains popularity in preclinical studies of AD...
February 8, 2019: Molecular Neurobiology
S Swarbrick, N Wragg, S Ghosh, Alexandra Stolzing
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood...
February 8, 2019: Molecular Neurobiology
Guendalina Olivero, Matteo Vergassola, Francesca Cisani, Cesare Usai, Anna Pittaluga
Mouse hippocampal glutamatergic nerve endings express presynaptic release-regulating NMDA autoreceptors (NMDARs). The presence of GluN1, GluN2A, GluN2B, and GluN3A subunits in hippocampal vesicular glutamate transporter type 1-positive synaptosomes was confirmed with confocal microscopy. GluN2C, GluN2D, and GluN3B immunopositivity was scarcely present. Incubation of synaptosomes with the anti-GluN1, the anti-GluN2A, the anti-GluN2B, or the anti-GluN3A antibody prevented the 30 μM NMDA/1 μM glycine-evoked [3 H]D-aspartate ([3 H]D-ASP) release...
February 7, 2019: Molecular Neurobiology
Nicolas Zink, Wiebke Bensmann, Larissa Arning, Ann-Kathrin Stock, Christian Beste
The cholinergic system is one of the most important neurotransmitter systems, but knowledge about the relevance of the cholinergic muscarinergic receptor system for cognitive functions is still scarce. Evidence suggests that the cholinergic muscarinic 2 receptor (CHRM2) plays an important role in the processing of cueing/prior information that help to increase the efficacy of lower-level attentional processes. In the current study, we investigated whether this is also the case for higher-level cognitive flexibility mechanisms...
February 7, 2019: Molecular Neurobiology
Hari Prasad Joshi, Sung Bum Kim, Seungki Kim, Hemant Kumar, Min-Jae Jo, Hyemin Choi, Juri Kim, Jae Won Kyung, Seil Sohn, Kyoung-Tae Kim, Jin-Ki Kim, In-Bo Han
The original version of this article, the name of author was incorrectely presented. That is Kyungjae Won (K. Won) should be presented as Jae Won Kyung (J.W. Kyung).
February 7, 2019: Molecular Neurobiology
Xuan T A Nguyen, Thanh Hoa Tran, Dan Cojoc, Giuseppe Legname
The cellular prion protein (PrPC ), mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neuritogenesis. In addition, its ability to bind copper or zinc has been suggested for its role in metal homeostasis. Although PrPC has been known as a copper-binding molecule, little is known about how copper can affect PrPC physiological functions. By combining genomic approaches, cellular assays, and focal stimulation technique, we found that PrPC neuritogenesis function is directly influenced by N-terminal copper-binding amino acids...
February 7, 2019: Molecular Neurobiology
Verónica M Borgonio-Cuadra, Claudia Valdez-Vargas, Sandra Romero-Córdoba, Alfredo Hidalgo-Miranda, Yessica Tapia-Guerrero, César M Cerecedo-Zapata, Oscar Hernández-Hernández, Bulmaro Cisneros, Jonathan J Magaña
Spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, is caused by a CAG repeat expansion in the ATXN7 gene coding region. Disease onset and progression are highly variable between patients, thus identification of specific/sensitive biomarkers that can improve the monitoring of disease progression is an immediate need. Because altered expression of circulating microRNAs (miRNAs) has been shown in various neurological diseases, they could be useful biomarkers for SCA7...
February 5, 2019: Molecular Neurobiology
Fang-Shin Nian, Lei-Li Li, Chih-Ya Cheng, Pei-Chun Wu, You-Tai Lin, Cheng-Yung Tang, Bo-Shiun Ren, Chin-Yin Tai, Ming-Ji Fann, Lung-Sen Kao, Chen-Jee Hong, Jin-Wu Tsai
Mutations in RAB18, a member of small G protein, cause Warburg micro syndrome (WARBM), whose clinical features include vision impairment, postnatal microcephaly, and lower limb spasticity. Previously, our Rab18-/- mice exhibited hind limb weakness and spasticity as well as signs of axonal degeneration in the spinal cord and lumbar spinal nerves. However, the cellular and molecular function of RAB18 and its roles in the pathogenesis of WARBM are still not fully understood. Using immunofluorescence staining and expression of Rab18 and organelle markers, we find that Rab18 associates with lysosomes and actively traffics along neurites in cultured neurons...
February 5, 2019: Molecular Neurobiology
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