Restoration of axotomy-induced PACAP gene induction in SCID mice with CD4+ T-lymphocytes

• Published in: Neuroreport Vol. 15; no. 17; pp. 2647 - 2650
• Main Authors: Armstrong, Brian D, Abad, Catalina, Chhith, Seririthanar, Rodriguez, Williams, Cheung-Lau, Gardenia, Trinh, Van, Waschek, James A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 03-12-2004; Lippincott Williams and Wilkins
• Subjects: Analysis of Variance; Animals; Axotomy - methods; Biological and medical sciences; CD4-Positive T-Lymphocytes - physiology; Development. Senescence. Regeneration. Transplantation; Facial Nerve - cytology; Facial Nerve - physiology; Flow Cytometry - methods; Functional Laterality - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; In Situ Hybridization - methods; Mice; Mice, Inbred BALB C; Mice, SCID; Motor Neurons - metabolism; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Neuropeptides - genetics; Neuropeptides - metabolism; Neurotransmitter Agents - genetics; Neurotransmitter Agents - metabolism; Pituitary Adenylate Cyclase-Activating Polypeptide; RNA, Messenger - metabolism; Transcriptional Activation; Vertebrates: nervous system and sense organs; Vertebrata; Axotomy; Mammalia; Mouse; Rodentia; T-Lymphocyte; Facial nerve; Lesion; Neuropeptide; Pituitary adenylate cyclase activating peptide
• ISSN: 0959-4965; 1473-558X
• DOI: 10.1097/00001756-200412030-00018

PACAP is a neuropeptide with putative neuroprotective, regenerative, and immunomodulatory actions. PACAP mRNA is up-regulated in motor neurons following facial nerve axotomy in wild type, but not immunodeficient SCID mice. Because CD4+ lymphocytes appear to be neuroprotective in facial nerve and other injury models, we studied PACAP gene expression in SCID mice preinfused with CD4+ enriched splenocytes. Whereas the mean number of PACAP hybridizing neurons after axotomy was reduced by 75% in uninfused SCID mice, infusion of CD4+ enriched splenocytes restored the number to a value not significantly different than controls. The CD4+ cell-dependent induction of PACAP in motor neurons may thus be a factor in the cascade of events triggered by immune cells that ultimately lead to nerve regeneration.