March 4, 2019Quiz
A neuron, also known as a nerve cell, is an electrically excitable cell that receives, processes, and transmits information through electrical and chemical signals. These signals between neurons occur via specialized connections called synapses. Neurons can connect to each other to form neural pathways, and neural circuits. Neurons are the primary components of the CNS or 1) ___ ___ ___, which includes the brain and spinal cord, and of the peripheral nervous system, which comprises the autonomic nervous system and the somatic nervous system.
There are many types of specialized neurons. Sensory neurons respond to one particular type of stimulus such as touch, sound, or light and all other stimuli affecting the cells of the sensory organs, and converts it into an electrical signal via transduction, which is then sent to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord in neural networks. A typical neuron consists of a 2) ___ body (soma), dendrites, and an axon. The term neurite is used to describe either a dendrite or an axon, particularly in its undifferentiated stage. Dendrites are thin structures that arise from the cell body, often extending for hundreds of micrometers and branching multiple times, giving rise to a complex dendritic tree. An axon (also called a nerve fiber) is a special cellular extension (process) that arises from the cell body at a site called the axon hillock and travels for a distance, as far as 1 meter in humans or even more in other species.
Most neurons receive signals via the 3) ___ and send out signals down the axon. Numerous axons are often bundled into fascicles that make up the nerves in the peripheral nervous system (like strands of wire make up cables). Bundles of axons in the central nervous system are called tracts. The cell body of a neuron frequently gives rise to multiple dendrites, but never to more than one axon, although the axon may branch hundreds of times before it terminates. At the majority of synapses, signals are sent from the axon of one neuron to a dendrite of another. There are, however, many exceptions to these rules: for example, neurons can lack dendrites, or have no axon, and synapses can connect an axon to another axon or a dendrite to another dendrite.
All neurons are electrically excitable, due to maintenance of voltage gradients across their membranes by means of metabolically driven ion pumps, which combine with ion channels embedded in the membrane to generate intracellular-versus-extracellular concentration differences of ions such as sodium, potassium, chloride, and calcium. Changes in the cross-membrane voltage can alter the function of voltage-dependent ion channels. If the voltage changes by a large enough amount, an all-or-none electrochemical pulse called an action potential is generated and this change in cross-membrane potential travels rapidly along the cell's 4) ___, and activates synaptic connections with other cells when it arrives. In most cases, neurons are generated by neural stem cells during brain development and childhood. Neurons in the adult brain generally do not undergo cell division.
The key to neural function is the synaptic signaling process, which is partly electrical and partly chemical. The electrical aspect depends on properties of the neuron's membrane. Like all animal cells, the cell body of every neuron is enclosed by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it. A lipid bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane are electrically active. These include ion channels that permit electrically charged ions to flow across the membrane and ion pumps that actively transport ions from one side of the membrane to the other. Most ion channels are permeable only to specific types of ions. Some ion channels are voltage gated, meaning that they can be switched between open and closed states by altering the voltage difference across the membrane. Others are chemically gated, meaning that they can be switched between open and closed states by interactions with chemicals that diffuse through the extracellular fluid. The interactions between ion channels and ion pumps produce a voltage difference across the membrane, typically a bit less than 1/10 of a volt at baseline. This voltage has two functions: first, it provides a power source for an assortment of voltage-dependent protein machinery that is embedded in the membrane; second, it provides a basis for electrical signal transmission between different parts of the membrane.
Neurons communicate by chemical and 5) ___ synapses in a process known as neurotransmission, also called synaptic transmission. The fundamental process that triggers the release of neurotransmitters is the action potential, a propagating electrical signal that is generated by exploiting the electrically excitable membrane of the neuron. This is also known as a wave of depolarization.
The biggest problem for brain repair is that neurons don't regenerate after brain damage, because they don't divide. In contrast, glial cells, which gather around damaged brain tissue, can proliferate after brain injury. Turning glial cells that are the neighbors of dead neurons into new neurons may be the best way to restore lost neuronal functions.
According to a paper published online in the journal Stem Cell Reports (7 February 2019), a combination of molecules that converts cells neighboring damaged neurons into functional new neurons, could potentially be used to treat stroke, Alzheimer's disease, and brain injuries. This treatment uses four small molecules which convert human astrocytes -- a common type of cell in the 6) ___ system -- into new neurons, which develop complex structures after four months. This drug combination has identified a set of four, or even three, molecules that could convert glial cells -- which normally provide support and insulation for neurons -- into new neurons. The authors previously published research describing a sequence of nine small 7) ___ that could directly convert human glial cells into neurons, but the large number of molecules and the specific sequence required for reprogramming the glial cells complicated the transition to a clinical treatment. In the current study, the team tested various numbers and combinations of molecules to identify a streamlined approach to the reprogramming of astrocytes, a type of glial cells, into neurons. The resulting chemically converted neurons can survive more than seven months in a culture 8) ___ in the lab. They form robust neural networks and send chemical and electrical signals to each other, as normal neurons do inside the brain. Using three of the small molecules instead of four also resulted in the conversion of astrocytes into neurons, but the conversion rate dropped by about 20%. The team also tried using only one of the molecules, but this approach did not induce conversion.
These authors also ad previously developed a gene therapy technology to convert astrocytes into functional neurons, but due to the excessive cost of gene therapy -- which can cost a patient half a million dollars or more -- the team has been pursuing more economical approaches to convert 9) ___ cells into neurons. The delivery system for gene therapies is also more complex, requiring the injection of viral particles into the human body, whereas the small molecules in the new method can be chemically synthesized and packaged into a pill. The authors acknowledged that many technical issues still need to be resolved before a drug using small molecules could be created, including the specifics of drug packaging and delivery. They also plan to investigate potential side effects of this approach in future studies in order to develop the safest drug pills. Nonetheless, the research team is confident that this combination of molecules has promising implications for future 10) ___therapies to treat individuals with neurological disorders.
Sources: Penn State, Simple drug combination creates new neurons from neighboring cells; In addition to Chen and Yin, other co-authors contributed to this work include Lei Zhang, Ning-Xin Ma, Yue Wang, Grace Lee, Xiao-Yi Hou, Zhuo-Fan Lei, Feng-Yu Zhang, Feng-Ping Dong and Gang-Yi Wu from Penn State. This work was supported by the National Institutes of Health (AG045656), the Alzheimer's Association (ZEN-15-321972), and the Charles H. Skip Smith Endowment Fund at Penn State; NIH.gov; ScienceDaily.com; Wikipedia
ANSWERS: 1) central nervous system; 2) cell; 3) dendrites; 4) axon; 5) electrical; 6) nervous; 7) molecules; 8) dish; 9) glial; 10) drug