Issue Cover & Information

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Issue Information

  • Pages: 2007-2009
  • First Published: 19 April 2022
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Cover Illustration

A 3D illustration of a neural network in the human nervous system, credited to Andrii Vodolazhskyi (Shutterstock, ID 536377753).

Editorial

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The brain—from neurodevelopment to neurodegeneration

  • Pages: 2010-2012
  • First Published: 19 April 2022
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In this Editorial, the contents of a Special Issue on Neurobiology are described by Andrey Abramov. The Special Issue features nineteen review articles that cover different aspects of the broad field of neuroscience from neurodevelopment, physiology, and memory formation to the mechanisms underlying the development of neurodegenerative diseases. We hope that readers will find these reviews interesting and informative.

State-of-the-Art Reviews

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The role of PARP1 in neurodegenerative diseases and aging

  • Pages: 2013-2024
  • First Published: 18 January 2021
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Poly (ADP-ribose)-polymerase-1 (PARP1), which has a prominent role in DNA damage response, can be post-translational modified in multiple fashions. PARP1 participates in various intracellular signal pathways and processes, including NAD+-SIRT1, neuroinflammation, mitochondrial dysfunction, and autophagy dysregulation. In this review, we summarized the recent research progresses on PARP1 as well as neurodegenerative diseases and aging.

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Heterotypic interactions in amyloid function and disease

  • Pages: 2025-2046
  • First Published: 18 January 2021
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Heterotypic interactions between amyloids, as well as with other proteins and macromolecules, contribute to a wide range of human pathologies, while hybrid amyloid complexes also serve important biological functions in all kingdoms of life. We review recent evidence on the role of sequence specificity, phase separation events and supersaturation in amyloid cross-talk and critically speculate on possible implications to important amyloid properties, such as cellular susceptibility, prion transmissibility and polymorphism.

Emerging Methods and Technologies

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Disease-specific interactome alterations via epichaperomics: the case for Alzheimer’s disease

  • Pages: 2047-2066
  • First Published: 24 May 2021
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This opinion piece presents our view how understanding interactome networks of complex diseases such as Alzheimer’s disease through epichaperomics may aid the transition from a limited single-alteration perspective in disease to a comprehensive network-based mindset. We posit a treatment paradigm may open and provide a previously unavailable precision medicine approach by understanding and targeting the interactome.

State-of-the-Art Reviews

Open Access

Bridging the gap between single receptor type activity and whole-brain dynamics

  • Pages: 2067-2084
  • First Published: 02 April 2021
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How single neuronal receptor types influence entire brain dynamics remains elusive. We propose a model that combines the brain’s anatomical and functional constraints with Michaelis–Menten kinetics at individual receptor sites, exemplified by the serotonergic (5-HT) system. Further, we show how optogenetic tools can be used for evaluation of our hypotheses in animal experiments. Our approaches may trigger new ways for the diagnosis and treatment of psychiatric disorders associated with malfunction of neurotransmitter systems.

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Complement cascade functions during brain development and neurodegeneration

  • Pages: 2085-2109
  • First Published: 18 February 2021
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Complement cascade activation engenders double-edged sword effects. During brain development, tightly regulated complement cascade promotes neural progenitor (NP) proliferation, migration and survival, and the removal of turnover apoptotic cells, cellular debris and unwanted synapses. Conversely, during pathological conditions, such as neurodegenerative disorders, uncontrolled complement cascade activation leads to chronic neuroinflammation characterized by sustained micro- and astrogliosis, increased pro-inflammatory mediator production, aberrant synaptic pruning and concomitant neuronal loss.

Open Access

Microglia phagocytose oligodendrocyte progenitor cells and synapses during early postnatal development: implications for white versus gray matter maturation

  • Pages: 2110-2127
  • First Published: 08 September 2021
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Early developmental amoeboid microglia (EDAM) found in the lateral ventricles invade the corpus callosum (CC), not the cerebral cortex. EDAMs phagocytose viable oligodendrocyte progenitor cells (OPCs) and lose their amoeboid shape at myelination onset. Fractalkine receptor-deficient mice exhibit a reduction in microglial phagocytosis of OPCs, increased numbers of oligodendrocytes, reduced myelin thickness, but no change in axon number suggesting that microglia phagocytose OPCs as a homeostatic mechanism for proper myelination.

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Understanding how kinesin motor proteins regulate postsynaptic function in neuron

  • Pages: 2128-2144
  • First Published: 18 November 2021
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Material transport to neuronal connections, namely synapses, is essential for neuronal activities and brain functions such as learning and memory. As the motor, kinesin family proteins not only directly transport various cargos to the postsynaptic compartment but also regulate cargo delivery through additional mechanisms. How kinesins transport specific cargos and how their functions are regulated by post-translational modifications (PTM) are potential directions for future research.

Open Access

Mechanisms of viral persistence in the brain and therapeutic approaches

  • Pages: 2145-2161
  • First Published: 12 April 2021
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This review focuses on the mechanisms of viral persistence in the CNS with particular considerations for how (1) virus enters the CNS via multiple routes, (2) within the CNS the virus can evade the adaptive immune responses and suppress innate immune responses, and (3) upon infection of glial cells and neurons, viruses can adapt to efficiently survive and transmit via cell to cell contact within the CNS.

Open Access

Cannabinoid control of hippocampal functions: the where matters

  • Pages: 2162-2175
  • First Published: 11 May 2021
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Hippocampal cannabinoid signaling regulates a plethora of cognitive functions. This review discusses the existent literature highlighting the relevance of the cannabinoid receptors expression in different cell types and intracellular compartments in hippocampal circuits. The different colors exemplify the multimodal, and sometimes opposite effects produced after hippocampal cannabinoid action. Thus, the functional dissection of hippocampal cannabinoid receptors is crucial to further understand brain disorders and age-related pathologies.

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Long-term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses

  • Pages: 2176-2201
  • First Published: 10 June 2021
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Synaptic plasticity permits bidirectional modification of synapses and likely is a cellular correlate of learning and memory. Synaptic tagging and capture enables synapses to interact with one another, underpinning associative learning. We describe how several key molecular players and cellular events promote, restrict or modulate homosynaptic and heterosynaptic forms of plasticity. Focusing on the hippocampus, we discuss recent advances in synaptic plasticity, its molecular interactions and behavioural implications.

Open Access

Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms

  • Pages: 2202-2218
  • First Published: 17 April 2021
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Astrocytes regulate hippocampal synaptic plasticity in an activity- and circuit-dependent manner. In this review, we discuss the molecular and cellular bases of such region-specific regulation of astrocyte–synapse interactions in the adult hippocampal circuitry. Importantly, the activation of astrocytic signaling is important for hippocampal synaptic homeostasis and thus memory processes. Meanwhile, dysregulation of this signaling can result in hippocampal circuit dysfunction and cognitive impairment during the progression of Alzheimer's disease.

Open Access

Brain-specific functions of the endocytic machinery

  • Pages: 2219-2246
  • First Published: 25 April 2021
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In this review, Camblor-Perujo and Kononenko outline basic mechanisms of endocytosis and summarize the current state of knowledge with respect to the functions of endocytic machinery in the brain, focusing on three main types of brain cells: neuronal progenitor cells, neurons, and glial cells.

Free Access

AMPK in the brain: its roles in glucose and neural metabolism

  • Pages: 2247-2262
  • First Published: 06 August 2021
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The AMPK αβγ heterotrimeric enzyme maintains energy balance in the brain and peripheral tissues. Glutamate release upon neuronal excitation allows astrocytic AMPK activation, stimulation of glycolysis through GLUT1 upregulation and glucose import, and release of lactate used for neuronal-oxidative metabolism. Exercise, hormones, and metabolites modulate brain region-specific AMPK activity to regulate feeding, thermogenesis, and neuronal energy balance.

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Interpreting the role of the striatum during multiple phases of motor learning

  • Pages: 2263-2281
  • First Published: 11 May 2021
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Motor learning requires transitions between four phases. The first phase involves random actions driven by motivation. The second phase involves insightful behavior, when a subject links a motor action with a goal and begins to repeat the action. In the third phase, motor activity is optimized. In the fourth phase, the goal-directed action becomes a skill or a habit, and activity shifts from dorsomedial to dorsolateral striatum.

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Protein synthesis as a modifiable target for autism-related dendritic spine pathophysiologies

  • Pages: 2282-2300
  • First Published: 29 January 2021
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Autism spectrum disorder (ASD) is clinically and neurobiologically heterogeneous. Monogenic ASDs with hyperactive mTOR emerged as a prototype of protein oversynthesis and inspired therapeutic approaches to suppress protein synthesis. In this review, we focus on the opposite end of the spectrum at molecular and synaptic levels. Integrating evidence from preclinical models, we propose a subgroup of ASD presenting with insufficient protein synthesis and decreased dendritic spine density.

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Soma-to-germline transformation in chromatin-linked neurodevelopmental disorders?

  • Pages: 2301-2317
  • First Published: 13 September 2021
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Chromatin is the 3D structure of our genome and consists of DNA wrapped around histone proteins. Mutations in numerous chromatin regulators cause neurodevelopmental disorders (NDDs), yet we do not know why. We found a subset of NDDs show loss of germline gene suppression in the brain; however, their impact is unknown. Ectopic expression of these deleterious sperm and egg genes during development may impair brain development and function.

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Interneuron development and dysfunction

  • Pages: 2318-2336
  • First Published: 12 April 2021
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The diversity of cortical interneurons is contributed by sequential events, such as fate specification, migration, positioning, morphogenesis, and synaptogenesis, and tightly modulated by intrinsic factors, extrinsic cues, and activity influences. Abnormalities of interneuron development lead to dysfunction of inhibitory circuits, which are highly associated with neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and intellectual disability. In this review, we discuss recent findings on interneuron development and interneuron dysfunction in neurodevelopmental disorders.

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Myeloid cells in retinal and brain degeneration

  • Pages: 2337-2361
  • First Published: 03 September 2021
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Myeloid cells can either play a protective role or hasten disease progression in pathogenic processes impacting vision. Mechanistic similarities exist across multiple degenerative diseases including glaucoma, age-related macular degeneration, retinitis pigmentosa, posterior uveitis, Alzheimer’s disease, and Parkinson’s disease. In addition to reviewing key studies defining important mediators of ocular inflammation, a class of medications with therapeutic promise, the glucagon-like peptide-1 receptor agonists, is also highlighted.

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AgRP neurons: Regulators of feeding, energy expenditure, and behavior

  • Pages: 2362-2381
  • First Published: 01 September 2021
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Agouti-related peptide (AgRP) neurons in the brain play an important role in the regulation of energy homeostasis. In this review, we describe our growing understanding of how AgRP neurons integrate nutrient, hormonal, sensory, and environmental input to mediate control over feeding, metabolic, and behavioral responses.

Table of Contents

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Table of Contents

  • Pages: 2382
  • First Published: 19 April 2022