TY - JOUR
T1 - Serotonin axons in the neocortex of the adult female mouse regrow after traumatic brain injury
AU - Kajstura, Tymoteusz J.
AU - Dougherty, Sarah E.
AU - Linden, David J.
N1 - Funding Information:
These experiments were inspired by the long-standing investigations of our collaborator and dear colleague Mark Molliver, who died in 2012. Thanks to Yunju Jin for performing virus injections, Devorah Vanness for help with image analysis, the laboratory of Alan Faden for demonstrating their CCI protocol, and Robert Cudmore for providing useful ideas. The authors, reviewers and editors affirm that in accordance to the policies set by the Journal of Neuroscience Research, this manuscript presents an accurate and transparent account of the study being reported and that all critical details describing the methods and results are present.
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/4
Y1 - 2018/4
N2 - It is widely held that injured neurons in the central nervous system do not undergo axonal regrowth. However, there is mounting evidence that serotonin axons are a notable exception. Serotonin axons undergo long-distance regrowth in the neocortex after amphetamine lesion, and, following a penetrating stab injury, they can regrow from cut ends to traverse the stab rift. Traumatic brain injury (TBI) is clinically prevalent and can lead to pathologies, such as depression, that are related to serotonergic dysfunction. Thus, whether serotonin axons can regrow after TBI is an important question. We used two models for TBI—a persistent open skull condition and controlled cortical impact—to evoke injury in adult female mouse neocortex, and assessed serotonin axon density 1 week, 1 month, and 3 months after injury by serotonin transporter immunohistochemistry. We found that after both forms of TBI, serotonin axon density is decreased posterior but not anterior to the injury site when measured in layer 1 at 1 week post surgery, and that serotonin axons are capable of regrowing into the distal zone to increase density by 1 month post surgery. This pattern is consistent with the anterior-to-posterior course of serotonin axons in the neocortex. TBI in these models is associated with significant reactive astrogliosis both anterior and posterior to the impact, but the degree of reactive astrogliosis is not correlated with serotonin axon density when measured 1 week after TBI. Microglial density remains constant following both types of injuries, but microglial condensation was detected 1 week after controlled cortical impact.
AB - It is widely held that injured neurons in the central nervous system do not undergo axonal regrowth. However, there is mounting evidence that serotonin axons are a notable exception. Serotonin axons undergo long-distance regrowth in the neocortex after amphetamine lesion, and, following a penetrating stab injury, they can regrow from cut ends to traverse the stab rift. Traumatic brain injury (TBI) is clinically prevalent and can lead to pathologies, such as depression, that are related to serotonergic dysfunction. Thus, whether serotonin axons can regrow after TBI is an important question. We used two models for TBI—a persistent open skull condition and controlled cortical impact—to evoke injury in adult female mouse neocortex, and assessed serotonin axon density 1 week, 1 month, and 3 months after injury by serotonin transporter immunohistochemistry. We found that after both forms of TBI, serotonin axon density is decreased posterior but not anterior to the injury site when measured in layer 1 at 1 week post surgery, and that serotonin axons are capable of regrowing into the distal zone to increase density by 1 month post surgery. This pattern is consistent with the anterior-to-posterior course of serotonin axons in the neocortex. TBI in these models is associated with significant reactive astrogliosis both anterior and posterior to the impact, but the degree of reactive astrogliosis is not correlated with serotonin axon density when measured 1 week after TBI. Microglial density remains constant following both types of injuries, but microglial condensation was detected 1 week after controlled cortical impact.
KW - controlled cortical impact
KW - regeneration
KW - serotonin
KW - traumatic brain injury
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U2 - 10.1002/jnr.24059
DO - 10.1002/jnr.24059
M3 - Article
C2 - 28485037
AN - SCOPUS:85019051219
SN - 0360-4012
VL - 96
SP - 512
EP - 526
JO - Journal of neuroscience research
JF - Journal of neuroscience research
IS - 4
ER -