Disruption of raphe serotonergic neural projections to the cortex: a potential pathway contributing to remote loss of brainstem neurons following neonatal hypoxic-ischemic brain injury

Reinebrant, Hanna E., Wixey, Julie A. and Buller, Kathryn M. (2012) Disruption of raphe serotonergic neural projections to the cortex: a potential pathway contributing to remote loss of brainstem neurons following neonatal hypoxic-ischemic brain injury. European Journal of Neuroscience, 36 11: 3483-3491. doi:10.1111/j.1460-9568.2012.08276.x


Author Reinebrant, Hanna E.
Wixey, Julie A.
Buller, Kathryn M.
Title Disruption of raphe serotonergic neural projections to the cortex: a potential pathway contributing to remote loss of brainstem neurons following neonatal hypoxic-ischemic brain injury
Formatted title
Disruption of raphé serotonergic neural projections to the cortex: a potential pathway contributing to remote loss of brainstem neurons following neonatal hypoxic-ischemic brain injury
Journal name European Journal of Neuroscience   Check publisher's open access policy
ISSN 0953-816X
1460-9568
Publication date 2012-12
Sub-type Article (original research)
DOI 10.1111/j.1460-9568.2012.08276.x
Volume 36
Issue 11
Start page 3483
End page 3491
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell
Collection year 2013
Language eng
Formatted abstract
Neuronal injury is a key feature of neonatal hypoxic-ischemic (HI) brain injury. However, the mechanisms underpinning neuronal losses, such as in the brainstem, are poorly understood. One possibility is that disrupted neural connections between the cortex and brainstem may compromise the survival of neuronal cell bodies in the brainstem. We investigated whether brainstem raphé serotonergic neurons that project to the cortex are lost after HI. We also tested if neuroinflammation has a role in disrupting brainstem raphé projections. Postnatal day 3 (P3) rats underwent unilateral carotid artery ligation followed by hypoxia (6% oxygen for 30min). A retrograde tracer, choleratoxin b, was deposited in the motor cortex on P38. On P45 we found that retrogradely labelled neurons in the dorsal raphé dorsal, ventrolateral, interfascicular, caudal and ventral nuclei were lost after P3 HI. All retrogradely labelled neurons in the raphé nuclei were serotonergic. Numbers of retrogradely labelled neurons were also reduced in the ventromedial thalamus and basolateral amygdala. Minocycline treatment (45mg/kg 2h post-HI, 22.5mg/kg daily P4-P9) attenuated losses of retrogradely labelled neurons in the dorsal raphé ventrolateral, interfascicular and ventral raphé nuclei, and the ventromedial thalamus. These results indicate that raphé neurons projecting to the cortex constitute a population of serotonergic neurons that are lost after P3 HI. Furthermore, neuroinflammation has a role in the disruption of raphé and thalamic neural projections. Future studies investigating the cellular mechanisms of axonal degeneration may reveal new targets for interventions to prevent neuronal losses after neonatal HI. Neuronal injury is a key feature of neonatal hypoxic-ischemic (HI) brain injury. The mechanisms underpinning neuronal losses, such as in the brainstem, are poorly understood.
Keyword 5-HT
Neuroinflammation
Rat
Retrograde transport
Tract tracing
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
 
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Created: Mon, 08 Oct 2012, 10:17:59 EST by Julie Wixey on behalf of School of Medicine