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Journal of Experimental Neuroscience

Alain Dagher, Yashar Zeighami
One of the most exciting recent hypotheses in neurology is that most neurodegenerative diseases are caused by the neuron to neuron propagation of prion-like misfolded proteins. In Parkinson disease, the theory initially emerged from postmortem studies demonstrating a caudal-rostral progression of pathology from lower brainstem to neocortex. Later, animal studies showed that the hallmark protein of PD, α-synuclein, exhibited all the characteristics of a prion. Here, we describe our work using human neuroimaging to test the theory that PD pathology advances via a propagating process along the connectome...
2018: Journal of Experimental Neuroscience
Sarah J Catchlove, Todd B Parrish, Yufen Chen, Helen Macpherson, Matthew E Hughes, Andrew Pipingas
Cerebrovascular reactivity (CVR) reflects the response of brain blood vessels to vasoactive stimuli, such as neural activity. The current research assessed age-related changes in regional CVR to 5% CO2 inhalation in younger (n = 30, range: 21-45 years) and older (n = 29, range: 55-75 years) adults, and the contribution of regional CVR to cognitive performance using blood-oxygen-level dependent contrast imaging (BOLD) functional magnetic resonance imaging (fMRI) at 3T field strength. CVR was measured by inducing hypercapnia using a block-design paradigm under physiological monitoring...
2018: Journal of Experimental Neuroscience
Myrto Denaxa, Guilherme Neves, Juan Burrone, Vassilis Pachnis
The mammalian cortex consists of two main neuronal types: the principal excitatory pyramidal neurons (PNs) and the inhibitory interneurons (INs). The interplay between these two neuronal populations - which drive excitation and inhibition (E/I balance), respectively - is crucial for controlling the overall activity in the brain. A number of neurological and psychiatric disorders have been associated with changes in E/I balance. It is not surprising, therefore, that neural networks employ several different mechanisms to maintain their firing rates at a stable level, collectively referred as homeostatic forms of plasticity...
2018: Journal of Experimental Neuroscience
Jihwan Myung, Dean Wu, Valérie Simonneaux, Timothy Joseph Lane
Cerebrospinal fluid (CSF) is a fluidic part of the brain's microenvironment that isolates the brain from the rest of the body. CSF dilutes metabolites from neuronal activities and removes them from the brain. Its production and resorption are regulated dynamically and are central to maintaining brain homeostasis. We discovered that the major CSF source, the choroid plexus (CP), harbors the brain's strongest circadian clock. Here, we consider some implications of the CP circadian clock for metabolite clearance in the brain...
2018: Journal of Experimental Neuroscience
Jérôme Munuera
Group living can help individuals defend against predators and acquire nutrition. However, conflicts between group members can arise (food sharing, mating, etc), requiring individuals to know the social status of each member to promote survival. In our recent paper, we sought to understand how the brain represents the social status of monkeys living in the same colony. Primates learn the social status of their peers through experience, including observation and direct interactions, just like they learn the rewarding or aversive nature of stimuli that predict different types of reinforcement...
2018: Journal of Experimental Neuroscience
Paul DE Williams, Jeffrey A Zahratka, Bruce A Bamber
Caenorhabditis elegans is a powerful model to study the neural and biochemical basis of behavior. It combines a small, completely mapped nervous system, powerful genetic tools, and a transparent cuticle, allowing Ca++ imaging without the need for dissection. However, these approaches remain one step removed from direct pharmacological and physiological characterization of individual neurons. Much can still be learned by "getting under the hood" or breaching the cuticle and directly studying the neurons...
2018: Journal of Experimental Neuroscience
Akanksha Mishra, Sonu Singh, Shubha Shukla
Dopamine controls various physiological functions in the brain and periphery by acting on its receptors D1, D2, D3, D4, and D5. Dopamine receptors are G protein-coupled receptors involved in the regulation of motor activity and several neurological disorders such as schizophrenia, bipolar disorder, Parkinson's disease (PD), Alzheimer's disease, and attention-deficit/hyperactivity disorder. Reduction in dopamine content in the nigrostriatal pathway is associated with the development of PD, along with the degeneration of dopaminergic neurons in the substantia nigra region...
2018: Journal of Experimental Neuroscience
Maria E Ramirez-Roman, Carlos E Billini, Alfredo Ghezzi
Alcohol addiction is a serious condition perpetuated by enduring physiological and behavioral adaptations. An important component of these adaptations is the long-term rearrangement of neuronal gene expression in the brain of the addicted individual. Epigenetic histone modifications have recently surfaced as important modulators of the transcriptional adaptation to alcohol as these are thought to represent a form of transcriptional memory that is directly imprinted on the chromosome. Some histone modifications affect transcription by modulating the accessibility of the underlying DNA, whereas others have been proposed to serve as marks read by transcription factors as a "histone code" that helps to specify the expression level of a gene...
2018: Journal of Experimental Neuroscience
Chitra D Mandyam, Sucharita S Somkuwar, Robert J Oliver, Yoshio Takashima
Addictive drugs effect the brain reward circuitry by altering functional plasticity of neurons governing the circuits. Relapse is an inherent problem in addicted subjects and is associated with neuroplasticity changes in several brain regions including the hippocampus. Recent studies have begun to determine the functional significance of adult neurogenesis in the dentate gyrus of the hippocampus, where new neurons in the granule cell layer are continuously generated to replace dying or diseased cells. One of the many negative consequences of chronic methamphetamine (METH) abuse and METH addiction in rodent and nonhuman primate models is a decrease in neural progenitor cells in the dentate gyrus and reduced neurogenesis in the granule cell layer during METH exposure...
2018: Journal of Experimental Neuroscience
Cynthia K McClard, Benjamin R Arenkiel
The brain is a remarkable network of circuits dedicated to sensory integration, perception, and response. The computational power of the brain is estimated to dwarf that of most modern supercomputers, but perhaps its most fascinating capability is to structurally refine itself in response to experience. In the language of computers, the brain is loaded with programs that encode when and how to alter its own hardware. This programmed "plasticity" is a critical mechanism by which the brain shapes behavior to adapt to changing environments...
2018: Journal of Experimental Neuroscience
Alexander Maxan, Francesca Cicchetti
There is compelling evidence that a number of neurodegenerative diseases share common pathogenic mechanisms. Better understanding these mechanisms will allow us to develop new therapeutic strategies. This commentary follows up on our recent findings that tau pathology can be found in healthy fetal tissue transplanted into the brain of patients with either Huntington or Parkinson disease. We will examine how tau appears to be shared in a number of different conditions and how its expression relates to cognitive decline and disease progression...
2018: Journal of Experimental Neuroscience
Bhavana Muralidharan, Leora D'Souza, Shubha Tole
We established an efficient cell culture assay that permits combinatorial genetic perturbations in hippocampal progenitors to examine cell-autonomous mechanisms of fate specification. The procedure begins with ex vivo electroporation of isolated, intact embryonic brains, in a manner similar to in utero electroporation but with greatly improved access and targeting. The electroporated region is then dissected and transiently maintained in organotypic explant culture, followed by dissociation and plating of cells on coverslips for in vitro culture...
2018: Journal of Experimental Neuroscience
Areeba Patel, Farooq Ali Khan, Arindam Sikdar, Amit Mondal, Sunil Dutt Shukla, Sukant Khurana
Phytomedicine has often been used as "alternative therapy," which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply "working" through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds...
2018: Journal of Experimental Neuroscience
Antonio Mateus-Pinheiro, Nuno Dinis Alves, Nuno Sousa, Luisa Pinto
Since the recognition that the mammalian brain retains the ability to generate newborn neurons with functional relevance throughout life, the matrix of molecular regulators that govern adult neurogenesis has been the focus of much interest. In a recent study published in Molecular Psychiatry , we demonstrate Activating Protein 2γ (AP2γ), a transcription factor previously implicated in cell fate determination in the developing cortex, as a novel player in the regulation of glutamatergic neurogenesis in the adult hippocampus...
2018: Journal of Experimental Neuroscience
Artem P Gureev, Ekaterina A Shaforostova, Anatoly A Starkov, Vasily N Popov
β-guanidinopropionic acid (β-GPA) has been used as a nutritional supplement for increasing physical strength and endurance with positive and predictable results. In muscles, it works as a nonadaptive stimulator of mitochondria biogenesis; it also increases lipid metabolism. There are data indicating that β-GPA can be also neuroprotective, but its mechanisms of action in the brain are less understood. We studied the effects of β-GPA on animal behavior and mitochondrial biogenesis in the cortex and midbrain of mid-age healthy mice...
2018: Journal of Experimental Neuroscience
Kimitoshi Kimura, Hirohiko Hohjoh, Takashi Yamamura
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which myelin and oligodendrocytes are the main targets recognized by inflammatory CD4+ T cells reactive to myelin peptides. Regulatory CD4+ T (Treg) cells normally keep homeostasis of the immune system by inhibiting detrimental effects of inflammatory T cells. However, Treg cells are reduced in patients with MS for unknown reason. This commentary highlights a novel function of circulating exosomes to inhibit the differentiation of Treg cells in MS...
2018: Journal of Experimental Neuroscience
Susanna Ambrosio, Barbara Majello
The autophagy-lysosome pathway sustains cellular homeostasis and is a protective mechanism against neurodegenerative diseases. Recent findings highlight the role of the histone demethylases LSD1/LDM1A as a pivotal regulator of autophagy process, by controlling the mTORC1 cascade, in neuroblastoma cells. LSD1 binds to the promoter region of the SESN2 gene, where LSD1-mediated demethylation leads to the accumulation of repressive histone marks that maintain SESN2 expression at low levels. LSD1 depletion results in enhanced SESN2 expression and consequently mTORC1 inhibition, thereby triggering the induction of autophagy...
2018: Journal of Experimental Neuroscience
Danielle E Mor, Harry Ischiropoulos
In Parkinson's disease (PD), the loss of dopamine-producing neurons in the substantia nigra (SN) leads to severe motor impairment, and pathological inclusions known as Lewy bodies contain aggregated α-synuclein protein. The relationship of α-synuclein aggregation and dopaminergic degeneration is unclear. This commentary highlights a recent study showing that the interaction of α-synuclein with dopamine may be an important mechanism underlying disease. Elevating dopamine levels in mice expressing human α-synuclein with the A53T familial PD mutation recapitulated key features of PD, including progressive neurodegeneration of the SN and decreased ambulation...
2018: Journal of Experimental Neuroscience
Daniel Pensold, Geraldine Zimmer
The correct establishment of inhibitory circuits is crucial for cortical functionality and defects during the development of γ-aminobutyric acid-expressing cortical interneurons contribute to the pathophysiology of psychiatric disorders. A critical developmental step is the migration of cortical interneurons from their site of origin within the subpallium to the cerebral cortex, orchestrated by intrinsic and extrinsic signals. In addition to genetic networks, epigenetic mechanisms such as DNA methylation by DNA methyltransferases (DNMTs) are suggested to drive stage-specific gene expression underlying developmental processes...
2018: Journal of Experimental Neuroscience
Tanzila Mukhtar, Verdon Taylor
The cerebral cortex is composed of billions of morphologically and functionally distinct neurons. These neurons are produced and organized in a regimental fashion during development. The ability of neurons to encode and elicit complex cognitive and motor functions depends on their precise molecular processes, identity, and connectivity established during development. Elucidating the cellular and molecular mechanisms that regulate development of the neocortex has been a challenge for many years. The cerebral cortical neuronal subtypes are classified based on morphology, function, intrinsic synaptic properties, location, connectivity, and marker gene expression...
2018: Journal of Experimental Neuroscience
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