title: Astrocytes promote peripheral nerve injury-induced reactive synaptogenesis in the neonatal CNS.
abstract: Neonatal damage to the trigeminal nerve leads to "reactive synaptogenesis" in the brain stem sensory trigeminal nuclei. In vitro models of brain injury-induced synaptogenesis have implicated an important role for astrocytes. In this study we tested the role of astrocyte function in reactive synaptogenesis in the trigeminal principal nucleus (PrV) of neonatal rats following unilateral transection of the infraorbital (IO) branch of the trigeminal nerve. We used electrophysiological multiple input index analysis (MII) to estimate the number of central trigeminal afferent fibers that converge onto single barrelette neurons. In the developing PrV, about 30% of afferent connections are eliminated within 2 postnatal weeks. After neonatal IO nerve damage, multiple trigeminal inputs (2.7 times that of the normal inputs) converge on single barrelette cells within 3-5 days; they remain stable up to the second postnatal week. Astrocyte proliferation and upregulation of astrocyte-specific proteins (GFAP and ALDH1L1) accompany reactive synaptogenesis in the IO nerve projection zone of the PrV. Pharmacological blockade of astrocyte function, purinergic receptors, and thrombospondins significantly reduced or eliminated reactive synaptogenesis without changing the MII in the intact PrV. GFAP immunohistochemistry further supported these electrophysiological results. We conclude that immature astrocytes, purinergic receptors, and thrombospondins play an important role in reactive synaptogenesis in the peripherally deafferented neonatal PrV.
authors: Department of Anatomy and Neurobiology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
authors: Fu-Sun
authors: FS
authors: Lo
authors: Shuxin
authors: S
authors: Zhao
authors: Reha S
authors: RS
authors: Erzurumlu
mesh_terms: D000367:Age Factors; D000080924:Aldehyde Dehydrogenase 1 Family; D000588:Amines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001703:Biophysics; D002454:Cell Differentiation; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003423:Critical Period, Psychological; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D003714:Denervation; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005463:Fluoroacetates / Q000008:administration & dosage; D007839:Functional Laterality; D000077206:Gabapentin; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D050697:Retinal Dehydrogenase / Q000378:metabolism; D013569:Synapses / Q000473:pathology / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D061221:Trigeminal Nerve Injuries / Q000473:pathology* / Q000503:physiopathology; D014278:Trigeminal Nuclei / Q000473:pathology*; D014738:Vibrissae / Q000294:innervation; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D011508:Chondroitin Sulfate Proteoglycans; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D005463:Fluoroacetates; D005904:Glial Fibrillary Acidic Protein; D016708:Synaptophysin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; C014815:fluoroacetic acid; D000080924:Aldehyde Dehydrogenase 1 Family; C523119:Aldh1a1 protein, rat; D050697:Retinal Dehydrogenase; D003576:Electron Transport Complex IV